Functionalized hybrid magnetic catalytic systems on micro- and nanoscale utilized in organic synthesis and degradation of dyes

Herein, a concise review of the latest developments in catalytic processes involving organic reactions is presented, focusing on magnetic catalytic systems (MCSs). In recent years, various micro- and nanoscale magnetic catalysts have been prepared through different methods based on optimized reaction conditions and utilized in complex organic synthesis or degradation reactions of pharmaceutical compounds. These biodegradable, biocompatible and eco-benign MCSs have achieved the principles of green chemistry, and thus their usage is highly advocated. In addition, MCSs can shorten the reaction time, effectively accelerate reactions, and significantly upgrade both pharmaceutical synthesis and degradation mechanisms by preventing unwanted side reactions. Moreover, the other significant benefits of MCSs include their convenient magnetic separation, high stability and reusability, inexpensive raw materials, facile preparation routes, and surface functionalization. In this review, our aim is to present at the recent improvements in the structure of versatile MCSs and their characteristics, i.e., magnetization, recyclability, structural stability, turnover number (TON), and turnover frequency (TOF). Concisely, different hybrid and multifunctional MCSs are discussed. Additionally, the applications of MCSs for the synthesis of different pharmaceutical ingredients and degradation of organic wastewater contaminants such as toxic dyes and drugs are demonstrated.

Fatemeh Ganjali was born in Isfahan in 1994. She graduated from the Islamic Azad University of Shahreza (IAUSH) with a BSc in Applied Chemistry in 2018. She completed her M.Sc. in 2020 from Iran University of Science and Technology (IUST) in Nanochemistry as the top student. She became a PhD student in nanotechnology (Nano polymer) under the supervision of Prof. Ali Maleki at the Iran University of Science and Technology (IUST) in 2020. She is interested in nano-biotechnology research.
Amir Kashtiaray was born in Tehran in 1988. He graduated from Payame Noor University (PNT) with a BSc (2011). Then, he continued his academic study as an M.Sc. Student in Analytical Chemistry at the University of Science and Technology (IUST), and graduated in 2020. His achievements include more than 50 inventions, several gold and silver medals awarded from World Invention Exhibition, in addition to special prizes and 13 diplomas. Amir was introduced as the best inventor by different countries invention academies in 2010 and 2011. Several ISI publications are also another honor for him. He is the CEO of Kashtiaray Nano Technology (Founded by Amir in 2017). Currently, he is working on different projects at IUST, as a Senior Researcher focusing on drug development, drug delivery, high-tech pharmaceutical compounds, hyphenated techniques in chromatography and advanced methods in microextraction and sample preparation.

Introduction
The synthesis of pharmaceutical compounds as the foundation of the pharmaceutical industry conventionally requires complex synthetic routes. However, this problem can be alleviated by using appropriate catalysts in the synthetic process. [1][2][3][4] Also, the discharge of dangerous and toxic drugs in water, which has farreaching effects on the aquatic ecosystem and the health of living creatures, has become a major problem. One solution to this issue is to catalytically degrade drugs into low-risk components. However, separating homogeneous catalysts from the reaction medium is difficult, which is why recent research has focused on the use of heterogeneous catalytic systems. 5 Heterogeneous catalytic systems render the catalyst and products in separable phases to speed up the effortless separation and lessen the reaction time with a higher yield. 6 Generally, among the extensive and diverse collection of heterogeneous catalytic systems, magnetic catalytic systems (MCSs) have attracted increasing attention from scientists due to their substantial benets. [7][8][9] Also, nanomaterial-based catalysts are highly regarded owing to their high aspect ratio. [10][11][12] Initially, magnetic catalysts facilitate the purication and workup process. 13 As reported, for the removal of a magnetic catalyst, a simple process is to hold an external magnet under the reaction ask and decant the medium, where a magnetic eld of 20 emu † g À1 or higher is required. 14 Furthermore, in the case of utilizing nanoscale magnetic catalysts, high reaction yields are obtained using a small amount of nanocatalyst due to their high aspect ratio. These heterogeneous catalysts are affordable and satisfactory species for industrial applications. 15 Another reason to employ heterogeneous MCSs is their facile separation. Heterogeneous MCSs retain their stability even aer alternating recycling runs, as long as the structural stability of the catalyst is maintained. Indeed, metallic-based heterogeneous MCSs such as iron demonstrate no signicant decline in catalytic performance over several sequential recycling procedures, where thermogravimetric analysis can conrm these claims. 16 In addition, many studies have been devoted to functionalizing MCSs or combining them with other substances to enhance the functions and applications of catalytic systems. [17][18][19][20][21] Reportedly, a heterogeneous MCS, i.e., amine-functionalized aminonitriles via one-pot synthesis but also exhibited enhanced reusability and structural stability. 22 Considering that most MCSs are composed of inorganic or natural components, 23 they are environmentally benign and considered in the green chemistry spectrum. 24 The most renowned and forerunner species of MCSs is highly magnetic iron oxide nanoparticles (Fe 3 O 4 NPs) synthesized in an alkaline environment, i.e., pH > 11, via a facile co-precipitation route from Fe 2+ and Fe 3+ ions. The resulting Fe 3 O 4 NPs can be modied with an SiO 2 layer to inhibit the further oxidation of Fe 3 O 4 to the less magnetic Fe 2 O 3 species. The silica-coated Fe 3 O 4 NPs have several surface hydroxyl groups as active sites, which can bind to other species through covalent bonding. 25,26 Ferrites are another class that can form MCSs. Various ferrites such as zinc ferrite (ZnFe 2 O 4 ), nickel ferrite (NiFe 2 O 4 ), and cobalt ferrite (CoFe 2 O 4 ), with different dopants, can be employed in the preparation of MCS. These materials exhibit different properties, that is, Ni ions in NiFe 2 O 4 are easily exposed to reduction compared with the Fe ions. 27 ZnFe 2 O 4 has a narrow bandgap, moderate photocatalytic activity, and chemical and thermal stability. 28 CoFe 2 O 4 has average saturation magnetization, strong anisotropy, and excellent mechanical and chemical stabilities. 29 Together with these inorganic systems, well-suited, lightweight, and innately magnetic species such as pumice ‡ are utilized in MCSs. Another advantage of pumice is its highly porous structure, which is formed when gaseous species are emitted from it. 30,31 These moderate MCSs have caused pharmaceutical synthesis to proceed in aqueous media, which was previously done in organic solvents. Safari et al. designed Fe 3 O 4 located in the space between the lamellae and exterior surface of the montmorillonite (MMT) support, namely, MMT@Fe 3 O 4 , as an eco-friendly catalyst for the synthesis of indeno [1,2-b]indolone in aqueous media with gentle conditions, high yield, and convenient recovery. 32 Further, in another report, Pd NPs were immobilized on melamine-functionalized magnetic chitosan beads (Fe 3 O 4 /CS-Me@Pd) to catalytically reduce p-nitrophenol and to conduct Suzuki reaction in aqueous medium. 33 In this study, melamine played a particularly important role, which not only acts as a platform for the excellent surface distribution of Pd(II) but also strongly interacts with Pd(II) to minimize the leaching of the metal NPs. Another notable advantage of this work was its high catalytic activity, as authenticated by the high TON and TOF under mild conditions. Similarly, MCSs are vital for the degradation of pharmaceuticals with high yield in aqueous medium. As a remarkable example, Kargae et al. synthesized a ZnFe 2 O 4 @CMC nanobiocomposite to remove ciprooxacin (CIP), an antibiotic of the uoroquinolones group, with good removal efficiency (87%) in synthetic samples without introducing any extra oxidizing agents. This nanophotocatalyst followed the "green chemistry" protocols and showed good chemical stability aer ve times reuse. 34,35 Also, Taghavi et al. introduced the MCS FeNi 3 /SiO 2 / CuS for the photocatalytic degradation of tetracycline under simulated solar light. 36 Facile recyclability and advanced photocatalytic decomposition, which degrades complex cyclic compounds into simple linear ingredients, and ultimately turn them into CO 2 and H 2 O, are two remarkable points in their report.
Magnetic biochar (MBC) composites are members of MCSs, which exhibit advanced magnetic properties when loaded with magnetic NPs, together with the advantages of biochar such as eco-friendliness and biodegradable raw materials including biomass waste, sugarcane bagasse, rice straw, peanut shells, and herb remains. 37,38 For instance, Reddy et al. introduced two MBC systems with biodegradable raw materials, namely ironloaded rice husk biochar (Fe-RHB) and coir pith biochar (Fe-CPB) for the decomposition of Acid Red 1 (AR1) organic dye, which resulted in nearly complete decolorization. 39 Herein, we aim to focus on MCSs and their applications in the synthesis of different pharmaceuticals and degradation of organic pollutants (dyes and versatile drugs) with an overview of the latest related literature. Certainly, our purpose is to concisely review the current literature associated with catalytic systems consisting of magnetic components to pave the way for the synthesis of pharmaceutical compounds and their degradation. Also, we briey summarize hybrid and multifunctional MCSs. Besides, we discuss the various properties of MCSs such as magnetization, reusability, structural stability, turnover number (TON), and turnover frequency (TOF).

Classification of the magnetic micro-and nanostructures
Here, a classication of MCSs is presented to give a qualied overview on catalytic systems implemented for the synthesis of pharmaceutical compounds to detail the unique advantages in each case.

Magnetic metal oxides
Extensive studies on metallic particles have demonstrated their excellent properties in the catalytic, optical, electronic, magnetic, and antibacterial elds. 40 Moreover, metallic nanoparticles and metal oxides have attracted attention due to their unique structure, electrical conductivity and electrocatalytic activity. 41 Gold NPs enhance the therapeutic effects against tumors with low toxicity. 42 Besides, gold and silver particles are exploited in biomedicine and drug delivery. 43 Silver NPs are applied in tissue engineering, coating medical implants, and boosting injury curing according to their antimicrobial and anti-inammatory potential. 44 The wide application diversity such as catalysis, preparation of nanocomposites, and production of electronic pieces of noble metallic NPs such as Ag, Au, Pd, Cu, and platinum group in pure or alloy form has persuaded scientists to focus on investigating these species. 40,[45][46][47][48] One of the most famous and widely used species with ferrimagnetic properties is iron oxide magnetic nanoparticles (Fe 3 O 4 MNPs). Pure Fe 3 O 4 NPs are not usually utilized in electrochemical techniques because pure metallic NPs do not have sufficient chemical stability in air and are immediately oxidized. ‡ An igneous rock. Also, pure Fe 3 O 4 MNPs tend to form large aggregates due to their intense dipole-dipole attraction. Thus, approaches for the protection of MNPs during their synthesis and applications are of great importance. These methods vary from graing with organic parts to coating them with polymeric, organic, and inorganic layers such as silica or carbon. Furthermore, these coating layers promote the properties of MNP. Specically, the chemical stability of NPs prevents their aggregation and agglomeration, their toxicity is reduced, and the effective interactions or coactions between NPs with other particles or various ligands are enhances. Magnetic nanoparticles can be placed next to other nanoparticles in electrocatalytic applications and sensors. 41 MNPs are used in composite materials, which involves two main steps, i.e., preparation of MNPs, and then surface modication. Fe 3  MNPs to 54.04 emu g À1 for the catalyst. This magnetic catalyst was utilized in the synthesis of 5-substituted 1H tetrazole (Fig. 2) and benzamide (Fig. 3). As a crucial fact, this reaction started from the insertion of the nontoxic K 2 [Ni(CN) 4 ] inorganic azide source in aryl halide via a one-pot procedure. It should be highlighted that the metal leaching study for this system was negligible, as proven by hot ltration and ICP-AES tests, which conrmed the strong binding of palladium to the active sites on the surface of the catalyst. Consequently, due the low leaching and high stability and reusability of the catalyst, it could be recycled ve times without any reduction in its catalytic performance. In some cases, 99% yield was obtained for 5substituted 1H tetrazole and benzamide under the optimum condition of 5.7 h, which is comparable with long-time reactions in organic solvents.
The combination of pure metallic catalysts with magnetic agents through surface modication routes is considered in another approach. Herein, the active catalytic sites are together  196-212. 49 with the magnetic feature. As a related example, Elazab et al. proposed a highly active reduced graphene oxide-supported Pd/ Fe 3 O 4 NP catalyst with a uniform dispersion of palladium NPs on its surface. This catalyst exhibited very high catalytic activity under both batch and continuous reaction conditions with 100% conversion in the 4-bromobenzaldehyde Suzuki crosscoupling reaction with phenylboronic acid, as shown in Fig. 4. 50 The structural defects in graphene sheets enhanced the catalytic activity and the interactions with anchored NPs. The remarkable benets of adopting the ow chemistry method include a shorter reaction time and higher conversion rate and selectivity than the ordinary batch approach. As an important point, the reduction reaction conducted by microwave irradiation resulted in rapid heating of the reaction mixture.
Palladium inhibited the agglomeration of the products during the graphene oxide reduction process.
In another work, the focus was the core-shell structure of the Fe 3 O 4 magnetic core and SiO 2 protecting shell that, which was functionalized with ortho-phenylenediamine (PDA) and Pd ions to form (Fe 3 O 4 /o-PDA-Pd), as depicted in Fig. 5. 17 A general fact that should be considered in the case of core-shell structures owning a magnetic core is that a stronger external magnetic eld is required given that there is an inverse relationship between the core covering layers and its magnetic property.
MNPs are prepared via physical and chemical preparation routes. Physical methods such as ball milling can be divided into ordinary ball milling method 51 and high-energy ball milling method. 52 The chemical procedures for the preparation of  MNPs include co-precipitation, 53 hydrothermal, 54 pyrolysis, 55 sol-gel, 56 microemulsion, 57 sonochemical, 58 electrodeposition, 59 and polyol methods. 60 Ferrites as a member of ferrimagnetic ceramics with the general formula of MFe 2 O 4 (M signies bivalent metal ions including Mn, Fe, Co, Ni, Cu, and Zn) are well known because of their physical and magnetic properties, electrical resistance, high chemical stability, and low cost. [61][62][63] According to the initial crystal lattice of ferrites, their structures are garnet, hexagonal, and spinel. [64][65][66] Among these structures, normal and inverse spinel ferrites are very attractive. Cobalt and iron oxides have higher magnetic properties compared to other ferrites. The properties of cobalt ferrites can be altered by applying different methods such as chemical substitution, heat treatment, and sudden cooling. 67 Fig. 6 shows the characteristics, synthesis routes, and applications of CoFe 2 O 4 . 68 In the ferrites category, copper spinel ferrites (CuFe 2 O 4 ) are appealing candidates due to their strong anisotropy, high coercivity, acceptable magnetic saturation, and excellent mechanical and chemical stabilities at high temperatures. The other relevant superiorities of CuFe 2 O 4 MNPs include their simple modication, surface functionalization, and good reusability and catalytic activity. 69 In the study by Maleki et al., nanoscale ZnS/CuFe 2 O 4 was used as a magnetic hybrid heterogeneous catalyst via the co-precipitation approach, which was retrieved by an external magnet from the reaction mixture. This magnetic hybrid composite catalyzed 2,4,5-triaryl-1H-imidazoles. The other advantages of this synthesized catalyst were its cost-effectiveness and reusability for ve times in alternating cycles without any discernible reduction in its catalytic activity. 70 As one of the precious instances of the catalytic function of NiFe 2 O 4 for the synthesis of pharmaceutical components, Hamidinasab et al. prepared a magnetically recoverable organoacid-decorated NiFe 2 O 4 nanocatalyst for the multicomponent synthesis of some phthalazine-trione and benzo [4,5] imidazo[1,2-a]pyrimidine derivatives, which complied with green chemistry protocols (Fig. 7). 71 As previously stated, the abundant OH groups on TiO 2 -coated nickel ferrite NPs act as active sites to bond with (3-chloropropyl) trimethoxysilane. Subsequently, nucleophilic attack occurs between the chlorine leaving group on NiFe 2 O 4 @TiO 2 -chloropropylsilane and OH on diethanolamine (DEA) as a nucleophile. Lastly, another nucleophilic substitution takes place between the surface OH groups on nano-NiFe 2 O 4 @TiO 2 -SiO 2 -Pr-DEA and chlorine leaving group on chlorosulfonic acid to constitute the nano-NiFe 2 O 4 @TiO 2 -SiO 2 -Pr-DEA-OSO 3 H hybrid nanocatalyst. According to the formation of titania and other layers around the NiFe 2 O 4 core, the magnetic saturation decreased from 35.1 to 11.1 emu g À1 at high magnetic elds up to 8000 Oe. Both nano-NiFe 2 O 4 @TiO 2 -SiO 2 -Pr-DEA-OSO 3 H and neat NiFe 2 O 4 exhibited superparamagnetism. In this regard, it is reasonable to use neat NiFe 2 O 4 as an inorganic magnetic catalyst with higher magnetic saturation and more convenient workup due to the work reported by Kaviyarasu et al. 72 In their study, neat NiFe 2 O 4 was prepared via the microwave combustion method (MCM) and conventional combustion method (CCM). The magnetic saturation value at 10 000 Oe magnetic eld increased from 40.76 emu g À1 for CCM to 42.49 emu g À1 for MCM because of the narrow and limited distribution of NPs in MCM. Plenty of parameters affect saturation magnetization. Indeed, the magnetic saturation increases with the crystallinity of the NPs. 73 On the contrary, as stated by Dai et al., an increase in calcination temperature is inversely proportional to the saturation magnetization given that defects and strain are abundant in the product during the calcination process, although some are relieved throughout the procedure. 74 Elsewhere, as another type of MFe 2 O 4 , ZnFe 2 O 4 MNPs and alginic acid (as a biopolymer) nanocomposite were recently synthesized, as shown in Fig. 8, and applied in an efficient catalyst for the practical synthesis of 2-amino-3-cyano-4H-pyran derivatives. 75 The distinctive benets of this process are mild conditions, short reaction time, facile workup, high yield, and green synthesis procedure. As a disadvantage, the magnetic saturation of the prepared catalyst (17.06 emu g À1 ) was lower than the neat ZnFe 2 O 4 MNPs, which could be ascribed to the magnetically neutral alginic acid structure present in the catalyst. However, despite the decreased magnetic saturation of the catalyst, it could be simply separated from the reaction environment.

Magnetic frameworks
Metal-organic frameworks (MOFs) are novel porous materials composed of ions or clusters of metals linked to organic ligands with coordination bonds. MOFs are not only magnicent adsorbents but also catalysts due to their consistent distribution of single-site or extremely small metal species, high porous structure, large surface area, and abundant active sites. 76 Magnetic MOF nanocomposites are an example of materials with facile separation and improved catalytic activity. However, one of the main challenges that still need to be solved is how to assemble MOFs on the surface of MNPs without modifying their surface. 77 The combination of Fe3O4 nanoparticles with Fe-MOFs endows the composite catalyst some advantages, such as easy magnetic separation, reusability, and other enhancements such as photo-Fenton performance. Fe 3 O 4 nanoparticles can be in situ lodged into the MOF structure, acting as a magnetic core in magnetic MOF core-shell structures. 78 Bian et al. synthesized a novel hierarchical core-shell Fe 3 O 4 @PDA-Pd@[Cu 3 (BTC) 2 ] nanocomposite via a layer by layer assembly method, as shown in Fig. 9. 77 There are also magnetic frameworks with inserted secondrow transition metals. This inclusion extends the performance of these materials to various application ranges due to their advanced covalency, redox capability, and last-row spin-orbit coupling compared to their rst-row analogs. Mononuclear niobium and molybdenum sites in MOFs display a wide variety of second-and third-row transition metals for stronger magnetic coupling in frameworks. 79 The preferred method for the synthesis of magnetic MOFs is the solvothermal method, sometimes coupled with microwave and ultrasonication treatment. 78,80 Recently, Espallargas et al. synthesized 2D Fe-based magnetic MOF nanosheets named MUV-1-X via a liquid exfoliation method. The resulting crystalline layers had favourable lateral size and thickness, which retained the structural magnetic properties. 81 Besides, MOFs are well-dened solid structures to carry immobilized enzymes in a robust biocatalytic system. Enzymes are natural biocatalysts, demonstrating high selectivity and catalytic performances for the synthesis of chemicals and pharmaceuticals. Although the porosity of MOFs plays a vital role in their structure and performance, hierarchically porous MOFs introduce an adaptable pore distribution from the micro to meso-scale to provide better accessibility to immobilize large molecules such as enzymes. In the work by Zheng et al., they have prepared a magnetic hierarchically porous core-shell Fe 3 O 4 @MOF structure through the formation of modulatorinduced defects. Then, amidase was immobilized on this magnetic carrier. The properties of this magnetic MOF biocomposite were optimized, resulting in a high enzyme loading, high catalytic yield, thermal and storage stability, and reusability in comparison with the free enzyme and similar structures without hierarchical porosity. 82 In another investigation, Zhang et al. focused their efforts on the preparation of a magnetic metal-organic framework, NiFe 2 O 4 @MOF-5. NiFe 2 O 4 is a spinel ferrite structure with high saturation magnetization and strong chemical stability. The combination of ferrite and MOF resulted in excellent magnetic susceptibility, which allows easy separation and reusability. 83 Song et al. reported the synthesis of the (Fe 3 O 4 @Au@MIL-100(Fe)) structure via a reaction including three successive steps. These steps included a solvothermal reaction, Au seed-induced growth and low-temperature cycling self-assembly, as shown in Fig. 10. This magnetic nanocatalyst acted as a peroxide mimic for the catalytic oxidation of the 3,3,5,5-tetramethylbenzidine (TMB) substrate. A prevalent non-devastating analytical technique used in chemical and biological analyses is surface-enhanced Raman scattering. 84 The vibrational modes of a molecule show a unique and ngerprint-like spectrum in the SERS technique to show valuable inherent structural information. In situ SERS spectroscopy can be employed to monitor the whole reaction. However, MOFs themselves do not have excellent SERS enhancement ability. Thus, the use of MOF composites with noble metals can modify their signal enhancement ability. According to the distinctive structure and catalytic characteristics of an Fe-based magnetic MOF, under photo-irradiation with the assistance of ascorbic acid (AA), enhance photo-induced catalytic oxidation was achieved. 85 Covalent organic frameworks (COFs) are organic porous structures, which have strong couplings among their building blocks. According to their characteristics including high chemical and thermal stability, structural resilience, and simple surface modication, COFs can be applied in various applications such as sensors, gas storage systems, catalytic approaches and many others. The density of COFs is lower than that of MOFs, resulting in enhanced stability in different acidic and basic pH and redox conditions. COFs have high sustainability to endure rough conditions without losing their crystallinity and orderly structure. COFs are one of the best candidates for heterogeneous catalysis. They can act as a host for MNPs in host-guest supramolecular structures. COFs are well isolated to prevent the agglomeration of MNPs and their large spatial pore distribution and channel permeability allow access to catalytically active substances as a nanoreactor. MNPs have desirable properties, and thus have received signicant attention from scientists, ranging from effortless magnetic recovery, low toxicity, and the ability to have various morphologies to low cost. Thus, due to the excellent properties of MNPs and COFs, their combination as magnetic COFs uncovers a vast, fascinating world of materials. 86 Additionally, MNPs can enhance the efficiency of the procedure and reusability of the catalyst. Cai et al. synthesized a unique Gypsophila bouquet-shaped magnetic COF through facile mechanochemical grinding followed by crystallization. In this work, amino-functionalized Fe 3 O 4 nanoparticles were graed to the Tp monomer (COF monomer). Then, Tp and Pa-1 (another monomer) were combined, resulting the formation of the magnetic TpPa-1. This magnetic COF exhibited superparamagnetic property and a large surface area due to its porous structure. It was used to extract trace analytes such as polycyclic aromatic hydrocarbons (PAHs) from ecological samples. The preparation and function of the bouquet-like magnetic TpPa-1 sorbent are illustrated in Fig. 11. 87

Natural-based magnetic systems
Considering that green synthesis and biocompatibility are vital aspects in catalytic systems, the presence of natural-based environmentally friendly magnetic compounds appear to be suitable for scaling up procedures, simplicity in nal purication processes and use in industrial applications. Versatile natural species such as clays and polymers have become the focus of scientists aer biocompatibility. 30 Intrinsically magnetic natural species such as pumice, magnetite, hematite, ilmenite, and pyrrhotite (monoclinic Fe 7 S 8 ) are utilized in competent catalytic systems. Magnetite, iron(II and III) oxide, a with brownish-black color, has the highest magnetic properties among the natural-based minerals. The chemical composition of pure hematite (Fe 2 O 3 ) consists of about 70% iron and 30% oxygen by weight. Magnetite is used in magnetic-derived catalysts in various processes. Magnetite NPs are employed in biomedical, environmental, and ferrouid applications. [88][89][90] However, unlike magnetite, hematite has weak attraction to a magnetic eld. Hematite is applied as a pigment mineral, healing stone, and catalyst with magnetic separation ability. 91 Additionally, the paramagnetic ilmenite (FeTiO 3 ) and the ferrimagnetic pyrrhotite (monoclinic Fe 7 S 8 ) have emerged as great magnetically separable catalysts in different reactions. 92,93 Volcanic pumice magnetic particles (VPMPs) are light-colored, highly porous volcanic rocks with an intrinsic magnetic property of 30 emu g À1 . VPMPs are biocompatible and have high surface functionalization capacity. 94 Furthermore, the physical properties of VPMPs, such as lightweight porous structures, are well suited for ltration and concrete construction applications. The chemical structure of pumice consists of a silica network, aluminum oxide, and aluminum silicate, and similar to other minerals, it has small amounts of the other metal oxides. Also, pumice can be functionalized with other species due to its chemical structure and abundant OH groups. 95

Hybrid micro and nanoscale magnetic composites
Recently, organic-inorganic hybrid materials have been implicated as heterogeneous catalysts given that they exhibit the advantages of both homogeneous and heterogeneous catalysts in organic synthesis. 96 The chemically bonded hybrid materials have been described as materials with covalent or partially covalent bonds. Hybrid catalysts consist of two distinguished phases with completely different properties and functionalities, which have synergistic combinations to develop overall catalytic properties. 97 In one of the most recent reports, Sedaghat et al. introduced an efficient hybrid catalyst with antibacterial property for the synthesis of 5-substituted-1H-tetrazoles. 98 In this regard, a Cu 2+ -Schiff base complex was anchored on magnetic mesoporous silica NPs to form Fe 3 O 4 @MCM-41-SB-Cu (Fig. 12). The possibility to load high amounts of copper on the catalyst is due to the presence of many coordination sites in the bis-Schiff base ligand. Besides, a coordination bond is formed between the oxygen and nitrogen atoms of the supported Schiff base and Cu 2+ ions. Signicantly, the long catalyst linkers in this study resulted in easy access by the reactants to the active sites of the catalyst compared to the studies with short linkers.
From a mechanistic point of view, during the synthesis of 5substituted-1H-tetrazoles, the interaction between Cu 2+ ions and oxygen atoms of the aldehyde and nitrogen atoms of the nitrile increases the electrophilicity of the aldehyde and nitrile, respectively, which promotes further interactions. The high catalytic performance and non-toxicity of the Cu catalysts led to excellent catalytic yields (69-95%) in this reaction.
Ferrites can also act as the magnetic core of hybrid catalysts. As an example, a hybrid nanocomposite of organoacid-decorated NiFe 2 O 4 was prepared. The advantages of the used MNPs included not only their superparamagnetic behavior and effortless separation from the reaction environment, but also considerable surface area, low toxicity, good stability, and easy surface functionalization. 71 Another example of ferrites is CuFe 2 O 4 @Si-Imid-PMo, which consists of an acidic ionic liquid based on the imidazolium cation and phosphomolybdic acid anion, both immobilized on the CuFe 2 O 4 @SiO 2 core-shell magnetic structure (Fig. 13). 99 This catalyst was applied in the synthesis of 2,4,5-trisubstituted imidazole derivatives. Matching with previous studies involving several functionalization steps on a magnetic core, the magnetic saturation of this catalyst decreased from 25.85 to 24.1 emu g À1 under an applied magnetic eld of 10 4 Oe compared to the neat CuFe 2 O 4 , which is ascribed to its non-magnetic silica shell and immobilized ionic liquid. However, the magnetization of this catalyst was sufficient for easy magnetic separation. The CuFe 2 O 4 @Si-Imid-PMo catalyst improved the production of the intermediate during the reaction, while it increased the electrophilicity of the electrophiles according to its role as a Brønsted acid center.
In a recent study reported by Bodaghifard et al., a magnetic core-shell structure was functionalized by polymer for the green synthesis of 2-amino-3-cyanopyridine derivatives. 100 This hybrid heterogeneous catalyst contained poly N,N-dimethylanilineformaldehyde supported on Fe 3 O 4 @SiO 2 (PDMAF-MNPs), as depicted in Fig. 14. It should be noted that the reduction in magnetic saturation compared to its pure magnetic core is much greater in the case of polymer linkers compared to other short organic likers, as stated in a previous study. According to the silica shell and polymeric linker around Fe 3 O 4 , the magnetic saturation declined from 53.5 to 31.1 emu g À1 in high magnetic elds up to 8000.0 Oe. The unpaired electron pairs of nitrogen in this eco-friendly catalyst expedited the Knoevenagel condensation of benzaldehyde and malononitrile and also Michael addition of cyclohexanone by taking the hydrogen of its components to form intermediates and adducts in the synthesis of 2-amino-3-cyanopyridine derivatives. This catalyst resulted in efficient isolated yields in the range of 74-93%. This retrievable catalyst was recycled six times with no distinctive structural alteration and change in its catalytic behavior.
As another strategy, conventional biocompatible and naturally occurring catalysts are combined with magnetic particles through surface modication approaches. Consequently, the active sites of the catalyst also exhibit magnetic property. For example, Maleki et al. designed an efficient magnetic hybrid catalyst, as shown in Fig. 15, for the synthesis of biologically active polyhydroquinoline derivatives. 101 In the design of natural polymer-based hybrid catalysts, dextrin, which originates from natural polysaccharide resources, is benecial due to its many effective advantages such as abundant active functional groups, non-toxicity and biocompatibility, availability, environmentally friendly nature, ability to prevent unwanted side reactions, and stereoselectivity in some organic reactions. Thus, the question arises, how can magnetic dextrin effectively act as a hybrid biocatalyst in pharmaceutical synthesis reactions?
On the one hand, the convenient separation of the catalyst is ascribed to iron oxide MNPs with acceptable particle distribution, high surface area to volume ratio, and superparamagnetic feature. On the other hand, its abundant reactive functional groups give the catalyst the ability to interact with other organic components via hydrogen bonds derived from the its hydroxyl groups and the electronegative atoms of the functional groups in the other material. Accordingly, the electrophilicity of the designed materials would be enhanced, nally facilitating the reaction. The synthesis of polyhydroquinoline derivatives via the asymmetric Hantzsch reaction took advantage of this catalyst to overcome the limitations in previous studies such as tedious workup process, harsh reaction conditions, and unsafe catalysts by presenting an appropriate yield (70-95%), short reaction time (15-45 min), and ve times recycling. Also, polyhydroquinoline derivatives have numerous pharmaceutical applications, for example, vasodilators, anti-atherosclerotic, hepatoprotective, antitumor, bronchodilator, antidiabetic, and calcium channel blockers. 102 In another study, Ru 3+ and carboxymethylcellulose (CMC) in the magnetic Ru III @CMC/Fe 3 O 4 hybrid catalyst (Fig. 16) exhibited a noticeable synergistic effect during each step in the synthesis of polyhydroquinoline derivatives. 103 This advantage of the above-mentioned hybrid catalyst is attributed to the Ru 3+ Lewis acid, which can be chelated with the carboxyl and free hydroxyl groups of CMCs. Ru 3+ activated bketo ester (4) to facilitate further nucleophilic attack in the condensation of hydrazine (3). Also, it acts as a center through which an electron transfers to give the enol (B) form from keto (A). Besides, Ru 3+ and hydrogen bonding advance the Knoevenagel condensation of a carbonyl compound (1) with malononitrile (2). It should be noted that the Ru 3+ and hydroxyl groups of CMCs are active catalytic sites to promote the Michael addition of the reaction intermediates (B and C), as displayed in Fig. 17.
In the recent report on the use of hybrid catalysts for the synthesis of pharmaceuticals by Maleki et al., they demonstrated the use of an eco-friendly solid-state hybrid catalyst. 94 Specically, in this study, they successfully demonstrated the synergistic impacts of ultrasonic waves and a natural-based magnetic cellulose/pumice hybrid catalyst for the synthesis of 2,4,5-triarylimidazoles. The mechanism for the synthesis of imidazole with respect to the role of the catalyst is shown in Fig. 18. The hydroxyl groups on cellulose activate the carbonyl group of benzaldehyde (1) and benzil (3) to further form intermediate I and II, respectively. According to the physical aspects, the highly porous structure of pumice created good electronic interactions between the components due to its very high surface area. Finally, because of the magnetic property of pumice, the catalyst was recycled for ten successive runs without any signicant loss in its catalytic functionality. Reportedly, a heterogeneous hybrid nanocomposite was synthesized via the co-precipitation method. Although the catalytic activity of each component of the composite was not signicant, the hybrid structure showed much higher activities due to the composition of the materials. Alternatively, the reported hybrid structure offers characteristic properties and applications that are not achievable in each component alone. The synergistic effect of the metals and metal oxides in a hybrid catalyst scaffold expedites the organic reaction more efficiently. 70,104 Table 1 summarizes the information of some efficient magnetic catalytic systems, highlighting their target organic reactions and reaction yields.

Application of micro and nanoscale magnetic catalytic systems in the degradation of pharmaceutical compounds
In recent decades, the discharge of toxic substances, including inorganic heavy metals and organic contaminants such as pesticides, herbicides, dyes and pharmaceuticals in water and sewage has become major human and ecology issues. [125][126][127][128] Thus, a wide variety of water decontamination methods utilizing micro-and nano-adsorbents and/or photocatalysts have been developed. [129][130][131] In addition, microwave-and ultrasonic-assisted pollutants catalysis approaches have gained wide interest in this eld due to their synergistic effect of converging the dispersed microwave and ultrasound elds onto the reactive sites of the catalyst. 60,132,133 These synergetic methods produce thermal or discharge effects around the catalyst, which lead to the in situ degradation of contaminants. 134 Generally, microwave technology reduces the activation energy and organic reaction time due to the following reasons: rstly, the catalysts absorb microwaves to produce a thermal effect, which can create abundant hot spots to speed up organic reactions. Secondly, the coupling effects of microwaves and catalysts that have high wave absorption capacity result in a non-thermal effect, which can generate hydroxyl radicals with strong oxidation potential, leading to an enhancement in the oxidation rate of organic materials. As the most recent example, Riaz et al. prepared MnO 2 nanorods and ZnMn 2 O 4 nanostructures with hexagonal shapes for the microwave-assisted catalytic decomposition of 4-nitrophenol (p-NP) solution. 135 ZnMn 2 O 4 exhibited a high degradation efficiency of up to 85% in just 30 min. As displayed in Fig. 19a, similar to the photocatalytic degradation conducted under visible light, hot spots with high temperatures are produced on the ZnMn 2 O 4 absorbent upon exposure to microwave irradiation. The water and dissolved O 2 molecules produce cOH and Hc, and O 2 c À radicals by the heat absorbance from the hot spots, respectively.
Similarly, the ZnMn 2 O 4 absorbent contributes to producing more cOH and O 2 c À radicals. The electrons in the valence band (VB) of the ZnMn 2 O 4 absorbent are excited and transported to the conduction band (CB), which causes holes (h + ) in the VB and electrons (e À ) in the CB. The holes oxidize H 2 O to produce cOH and the electrons react with dissolved O 2 to produce O 2 c À . Eventually, this mechanism process facilitates the degradation of p-NP to CO 2 , H 2 O, and nitrate. According to the scavenging experiment results, it was found that the produced cOH radicals acted as the major active species in the decomposition compared to O 2 c À . Besides, the ZnMn 2 O 4 absorbent had a slight reduction in activity (from 83% to 79%) aer three successive p-NP microwave-assisted degradation cycles, as shown in Fig. 19b.
Another study was devoted to investigating the synergistic effect of ultrasound irradiation power, catalyst dosage, solution pH, etc. on tetracycline (TC) ultrasound-assisted degradation using Fe/N-C-x hybrid/H 2 O 2 Fenton-like catalysts (x stands for iron salt molar ratio (Fe(NO 3 ) 3 $9H 2 O)). 136 Unlike previous reports, the removal of TC decreased from 93.8 to only 86.3 in 80 min by altering the pH from 3 to 11, indicating that this catalyst has high removal efficiencies in a wide pH range (Fig. 20a). The TC degradation increased concurrently with an increase in Fe/N-C-2 concentration, which was attributed to the generation of more cOH radicals, resulting from the decomposition of H 2 O 2 (Fig. 20b). Terephthalic acid, as a uorescence probe, was employed to authenticate the amount of cOH radicals produced. A slight increase in the uorescence response was assigned to the hydroxyl radicals produced by Fe/N-C-2 catalysis (Fig. 20c). Given that one of the most effective parameters to achieve superior degradation efficiencies is ultrasound irradiation, different ultrasonic powers (0, 40, 60, 80, 100, and 120 W) were applied to monitor their effects on the system (Fig. 20d). The increase in ultrasonic power was observed to be directly proportional to the TC degradation efficiency, conrming the synergistic catalytic effect of the Fe/ N-C-2 catalyst and ultrasound waves.
Moreover, consecutive ultrasound exposure removed the byproducts; thus, the surface of the catalyst was free for further reactions. Furthermore, a higher ultrasonic power generates more cavitational bubbles with extremely high pressure and temperature, which collapse and produce solution turbulence, leading to elevated intensity of mixing between the catalyst and contaminant. 137 Nevertheless, it should be noted that an additional increase in ultrasonic power resulted in lower TC degradation because the maximum growth and collapse of the cavitation bubbles occur together with the compression cycle in the cavitation process, resulting in attenuated cavitation action at high ultrasound irradiation intensity. Accordingly, 80 W was chosen as the optimized ultrasonic power.
Precisely, various magnetic catalytic systems and the pioneering and most powerful photocatalysts are discussed briey. As the rst and foremost example of photocatalysts, TiO 2 is wellknown due to its chemical stability, non-toxicity, and comparatively low cost. As stated above, photocatalytic degradation is triggered when a photon is sufficiently excited to over the bandgap energy value of a semiconductor. Semiconductor  138 UV irradiation is the most potent energy source for the degradation of pollutants; however, it poses a risk to human health and has detrimental effects on the eyes. 139 Thus, various strategies have been developed to produce visible lightactive TiO 2 photocatalysts such as metal doping, 140 non-metal doping, 141 codoping with different semiconductors, 142 and dye sensitization. 143 The presence of metal dopants in the structure of TiO 2 delays the recombination of charge carriers by electron trapping, changing its bandgap energy and physical characteristics.
For instance, Ag co-doped TiO 2 nanostructures graed on Fe 3 O 4 NPs were synthesized through a facile and affordable coprecipitation approach. They were applied for the degradation of dibutyl phthalate (DBP), which is a toxic ecological pollutant (Fig. 21a). 144 The degradation intermediates such as butyl phthalate, diethyl phthalate, dipropyl phthalate, methyl benzoate, and benzoic acid were detected by gas chromatography/mass spectrometry (GC-MS) analysis, and the two possible decomposition routes are illustrated in Fig. 21b. During the reaction, the generated excitons by light stimulation of TiO 2 are transferred to the surface of the catalyst to react with OH À , O 2 , H 2 O, and other species. The cOH radicals break DBP in two possible ways, as follows: the rst way is to break the C-O bond of DBP to form monobutyl phthalate accompanied by the breakage of another C-O bond to produce phthalic acid.
The further decomposition of phthalic acid generates benzoic acid, which breaks into CO 2 and H 2 O. The second path is the degradation of the DBP molecules from various sides of its carbon chain to form dipropyl phthalate and diethyl phthalate as the main products. In the subsequent reaction stage, methyl benzoate and benzoic acid are generated by the actions of cOH radical. Similarly, benzoic acid degrades to CO 2 and H 2 O. The DBP degradation efficiency reached 74%, which remained almost the same aer ve cycles, proving the high stability and reusability of the catalyst.
Another strategy to simplify the degradation of pharmaceuticals using a catalytic system is to narrow the absorption range of TiO 2 to the visible light region. Besides the abovementioned method, another way includes doping non-metal species in the oxygen sites of the TiO 2 structure, creating oxygen defects, which reduce the bandgap energy of non-metal-doped TiO 2 and lowers the energy level of its VB. As an example, a nitrogen-  g À1 for Fe 3 O 4 to 30.45 emu g À1 for NTFS is attributed to the nonmagnetic SiO 2 layer and heating during the calcination process. However, NTSF was reused in four consecutive cycles without any signicant reduction in its efficiency. In general, as previously stated, reactive oxidative species (ROS) such as cOH, O 2 c À , h + , and e À promote photocatalytic reactions (Fig. 22a). Various scavenger agents were applied to evaluate the level of ROS participation in the photocatalytic reactions. The photocatalytic activity of NTSF in the degradation of NPX under the optimized conditions was investigated in the presence and absence of different scavengers (Fig. 22b). The greater the rate of degradation, the more effective role the radical plays in the degradation process. Ammonium oxalate (AO), benzoic acid (BA), p-benzoquinone (BQ), and K 2 Cr 2 O 7 are the appropriate scavengers for h + , cOH, O 2 c À , and e À , respectively. The degradation rate was considerably reduced with the addition AO, BQ, K 2 Cr 2 O 7 , and BA. Thus, it was concluded that the destruction of NPX was mainly conducted by cOH and h + played a minor role in the degradation process.
In a recent study by Sayadi et al., the degradation of naproxen (NPX) was conducted using ZnFe 2 O 4 @TiO 2 /Cu under solar light irradiation. 146 The participation of ZnFe 2 O 4 with a low bandgap of 2.11 eV in the composite photocatalyst caused it to possess a narrow bandgap of about 2.62 eV, which resulted in photocatalytic activity under visible light. Initially, to balance the total energy of the system, the electrons in the copper NPs transfer to  TiO 2 given that they have higher energy levels (Fig. 23). Simultaneously, when NPX contacts the ZnFe 2 O 4 @TiO 2 /Cu photocatalyst, the electrons in the VB of TiO 2 and ZnFe 2 O 4 transfer to their CB by excitation from sunlight irradiation. The fate of these stimulated electrons can be predicted in different ways. The produced electrons in the CB of TiO 2 by solar light irradiation are transferred to Cu. In the next step, they may rst transfer from the CB of ZnFe 2 O 4 to the CB of TiO 2 and then move to Cu.
Further, direct electron injection from the CB of ZnFe 2 O 4 to Cu NPs is plausible. Accordingly, the ZnFe 2 O 4 @TiO 2 /Cu photocatalyst can diminish the recombination rate of excitons. The holes in the VB of ZnFe 2 O 4 and TiO 2 are involved in the degradation of NPX and cOH generation, while the photogenerated electrons react with O 2 for the production of more O 2 c À . Lastly, the resultant drugs turn into H 2 O and CO 2 by cOH, O 2 c À , and h + radicals. This catalyst exhibited not only high removal efficiency for NPX (80.73%) but also exhibited superior reusability, where aer ve runs of degradation, 72.31% degradation was attained. In addition, facile recovery of this core-shell ZnFe 2 O 4 @TiO 2 /Cu structure was achieved due to its magnetic saturation of 26.45 emu g À1 , which is comparable with that of other magnetic TiO 2 photocatalysts.
Also, a magnetic TiO 2 -graphene oxide-Fe 3 O 4 composite was prepared by He et al. for the photo-Fenton decomposition of amoxicillin. 147 Although each structural moiety of this photocatalyst has its unique benecial properties, an excellent synergic effect occurred aer they were combined. For instance, graphene oxide (GO) with properties such as 2D carbonaceous monolayer structure, high surface area, and electrical conductivity was employed as a template for binding nanoparticles. Besides, Fe 3 O 4 has high chemical and thermal stability compared to other oxides and it aids the simple recovery of the catalyst. According, all these parts in the TiO 2graphene oxide-Fe 3 O 4 composite aimed to enhance the catalytic role, durability and separation property deciencies of TiO 2 by its combination with the high-conductive (GO) and highmagnetic recovery ability (Fe 3 O 4 ) of its components.
ZnO is another useful photocatalyst that contributes in catalytic systems to the degradation of organic contaminants. In a recent report, Maleki et al. prepared a ZnO/Fe 3 O 4 @pumice photocatalyst for the degradation of methylene blue (MB) under green light irradiation with a maximum photocatalytic efficiency of 85.5% (Fig. 24a). 148 As another strategy, the improvement in magnetic property obtained through composing magnetic pumice micro-plates and Fe 3 O 4 NPs was proved by the $20 emu g À1 increase in the magnetic saturation of Fe 3 O 4 @pumice at AE15 000 Oe magnetic eld. The simple retrievability of the photocatalyst for eight cycles was attributed to its high magnetic property. The same as-proposed mechanisms for TiO 2 and ZnO nanorods (NRs) was stimulated when exposed to green LED light.
Regarding the resemblance of the energy level of the CB of ZnO and Fe 3 O 4 , the same number of holes produced in their CB results from the electron transfer from the VB of ZnO to the VB of Fe 3 O 4 . This procedure somehow reduces the electron-hole pair recombination. Therefore, electron accumulation in the VB of ZnO enhances the production of O 2 c from the O 2 molecules in the air. Moreover, cOH radicals are generated from water during the oxidization process of the holes (h + ). In this report, erythrocyte sedimentation rate (ESR) analysis was performed to screen the formation of the cOH radical (Fig. 24b). Accordingly, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a conventional spin-trap reagent was applied. It was concluded that cOH radicals play a vital role in the degradation of MB compared to O 2 c radicals because there was no distinctive signal in the ESR spectrum when the reaction with ZnO/Fe 3 O 4 @pumice was carried out in the dark. However, the DMPO-OH adduct exhibited four quartet peaks under green-light exposure. Considering that the individual bandgap of ZnO is 3.32 to 3.37 eV, it absorbs UV radiation, which is not very favorable. Thus, the composition process with Fe 3 O 4 owing to its bandgap of 1.7 eV leads to more effective photocatalytic degradation and efficient energy harvesting ability in comparison with bare ZnO NRs.
It should also be noted that the contribution of magnetic nano spinel ferrites to 2D graphene family nanomaterials result in preferential properties compared to their individual catalytic systems. Graphene-based nano spinel ferrites (GNSFs) are potentially cost-effective and environmentally friendly materials and possess improved physical and chemical characteristics such as restrained particle aggregation, boosted active surface area, and simple magnetic removal for the recycling process. 149,150 These magnetic catalysts participate in both adsorptive and degradation reactions. 151 GNSFs show incomparably better adsorption efficiency than individual graphenebased nanomaterials, i.e., graphene, GO, and rGO. As a prominent example, rGO/Bi 2 Fe 4 O 9 displayed a maximum adsorption capacity (q m ) of 3.95 mg g À1 for bisphenol-A, which is signicantly higher than that of Bi 2 Fe 4 O 9 (0.74 mg g À1 ) and GO/ Bi 2 Fe 4 O 9 (1.72 mg g À1 ). 152 This remarkable result is related to the enhanced surface area of rGO ($2600 m 2 g À1 ) and p-p stacking interactions between the benzene ring of bisphenol-A and surface functional groups of rGO. GNSFs demonstrate a high degree of light-harvesting features and a broader visible light absorption spectrum because of the participation of graphene in magnetic catalytic systems. In the optimized state, it was found that as the graphene content increases, the absorption of visible light increases.
Regarding the study done by Liu et al., graphene in GNSFs acts as an acceptor and mediator agent for photogenerated electrons, which impedes the recombination of e À -h + pairs during the transition process. The role of rGO relies on its substantial p-p network, which retains the electrons, and its lower Fermi energy compared to the CB of ZnFe 2 O 4 . 153 Reportedly, manganese ferrite/graphene oxide (MFO-GO) was applied for the adsorption of MB from an aqueous solution with a maximum adsorption capacity (q m ) of about 177.3 mg g À1 (Fig. 25). 154 The magnetic saturation of the MFO NPs was 20 emu g À1 ; however, the magnetic saturation for MFO-GO was reduced with an increase in the GO content from 12.2 to 3.2 emu g À1 , altering the GO content from 10% to 50%, respectively. Also, MFO-GO showed excellent reusability aer ve cycles. From a mechanistic aspect, there are four possibilities for the removal of MB dye in neutral solution. The rst is associated with electrostatic/ionic interactions between the MB molecules with a positive charge and surface OH groups of GO and MFO. The second reason is assigned to the abundant active binding sites of the basal planes and GO edges, including carboxyl (-COOH), epoxy (C-O), and hydroxyl (-OH) oxygen-containing functional groups, which act as major adsorption sites for MB. The third factor is related to the p-p interactions between the C]C double bonds of MB and p electrons of the benzene ring with the p electrons on the surface of GO. The forth item to be considered is associated with the synergistic effect of adsorption and photocatalysis, which result in the degradation of MB. As other effective items, the Mn/Fe synergistic mechanism in MFO catalysts for the decomposition of MB should be considered. As stated above, by considering the critical role of GO, more oxygen-containing functional groups can be obtained by increasing the content of GO, which agrees with the results of enhanced adsorption activity. Thus, the adjustment of the GO content and MFO NPs in composite systems can ultimately optimize the MB adsorption mechanism.
In addition to the mentioned magnetic photocatalytic systems, magnetic biochar (MBC) from the biochar composite family not only exhibits the advantageous features of biochar (BC) but can also be magnetically separated from the reaction ask. 155 Moreover, due to the good contribution and dispersal of photocatalysts on the MBC support, their recovery and performance are enhanced, and their aggregation will be effectively inhibited. 156 MBC-catalyzed decomposition systems competently decrease the organic content of pollutants, which can be traced by total organic carbon (TOC) analysis. 157,158 Additionally, the degraded contaminants may be more noxious and toxic than the individual pollutants given that the mineralization of organic pollutants does not completely occur. 159 Fortunately, researchers have proven the detoxication effect of MBCcatalyzed degradation systems, which is an excellent feature compared to other degradation systems. 160 In a recent study conducted by Xie et al., a Bi 2 WO 6 /Fe 3 O 4 /BC photocatalyst was synthesized via a hydrothermal method to degrade ooxacin (OFL) and ciprooxacin (CIP) upon exposure to a visible LED. 161 The intermediate products of OFL and CIP exhibited less toxicity against Escherichia coli bacteria than the original pharmaceutical contaminants. As depicted in Fig. 26

Application of micro and nanoscale magnetic catalytic systems in the synthesis of pharmaceutical compounds
In recent decades, the use of catalytic systems and their functionalities have attracted great attention due to their benets in pharmaceutical synthesis for scaling up production. However, there are numerous issues in the eld of catalysis. These issues include environmental impact, process safety, mass and heat transfer restrictions, and optimizing reaction conditions, i.e., temperature, pressure, time, solvents, scaled-up procedures, reusability and stability, catalyst deactivation, and recovery. Among the catalytic systems, heterogeneous and magnetic catalysts meet the needs for convenient catalyst recovery from the reaction ask with only an external magnet. As a brilliant example, the Fe 3 O 4 /o-PDA-Pd nanocatalyst developed by Maleki et al. was applied in the Suzuki-Miyaura coupling reaction, in which biphenyls were prepared from aryl halides and phenylboronic acids, as shown in Fig. 27. 17 The active pharmaceutical biphenyl compounds resulting from this reaction, including losartan, urbiprofen, and taren-urbil, are used as resources to treat hypertension and diabetic nephropathy, 182 signs of osteoarthritis and rheumatoid arthritis, 183 and Alzheimer's disease and prostate cancer, 184 respectively. The surface functionalization through covalent bonding occurs between the amine functional group of PDA and chloropropyl carbons of silane, which are bonded to chlorine. Eventually, the unpaired electron pairs in the amines interact with the empty orbitals in Pd. Due to the reaction mechanism, the electron interactions among the three main components involving the oxygen atoms of aryl halides and phenylboronic acid and divalent palladium ions lead to the nal covalent binding. Subsequently, under basic conditions, Pd(II) was subjected to reduction to Pd(0) by sodium borohydride reducing agent. The reproducibility tests indicated ten times recycling for this catalyst without any reduction in its catalytic activity. It should be highlighted that by applying this catalyst in the Suzuki-Miyaura coupling reaction, approximately 98% yield was achieved in 10 min. In another study, Beitollahi et al. developed an environmentally friendly and facile method for the synthesis of an Fe 3 O 4 @cellulose nanocrystal/Cu nanocomposite (Fe 3 O 4 @-CNC/Cu). Henceforth, a graphite screen-printed electrode (GSPE) modied with Fe 3 O 4 @CNC/Cu was applied as a sensor for  41 Mo et al. developed a magnetic recyclable metal-organic framework catalyst. They synthesized cyclohexenone derivatives under solvent-free conditions. Cyclic enone derivatives are acknowledged to be precious intermediates in pharmaceuticals and natural products. Cyclohexanone units containing C]O and C]C groups in their structure exist in many synthetic and medicinally natural products such as the fungus A. avus YIM DT 10012, and Trachyspermum roxburghianum. Additionally, they can be applied in drugs, pesticides, and polymers. [185][186][187] As depicted in Fig. 29 and 30, Zhang et al. researched the catalytic solvent-free synthesis of cyclohexanone derivatives through aldehyde and acetoacetanilide condensation reactions utilizing the heterogeneous g-Fe 2 O 3 @SiO 2 /IRMOF-3 MOF catalyst. The catalyst was easily separated with an external magnet in this environmentally benign approach and retrieved several times without any changes in its catalytic activity. 188 Maleki et al. introduced magnetic pumice in a novel and well-designed magnetic composite, which led to the effortless recycle of the catalyst from the reaction mixture. In this work, palladium nanoparticles as the main catalytic active sites were

Review
Nanoscale Advances well-distributed on the VPMP@CLS structure. For the Suzuki-Miyaura cross-coupling catalytic reactions, as a heterogeneous catalytic system, the Pd 2+ nanoparticles were reduced to Pd-and biphenyl pharmaceutical derivatives were produced. This product has high importance in pharmaceutical compounds. It can be applied in cancer therapy and treatment of arteriosclerosis, osteolytic disorders, and ophthalmic disorders, and used as integrin antagonists. 30 In another study by Maleki et al., a pumice magnetic volcanic rock and cellulose matrix nanocomposite was synthesized. This heterogeneous biodegradable nanocomposite was employed in the synthesis of 1,4dihydropyridine derivatives, and the reaction outline is presented in Fig. 31. Given that 1,4-dihydropyridine derivatives have a wide variety of applications in antihypertensive and anticancer drugs, there synthesis procedures require signicant consideration. 189 Based on the advantages of heterogeneous hybrid magnetic nanocatalysts, organo-sulfonic acid tags attached to magnetic titania-coated NiFe 2 O 4 nanoparticles were employed to form nano-NiFe 2 O 4 @TiO 2 -SiO 2 -Pr-DEA-OSO 3 H nanocatalysts to advance the green synthesis process. 71 In this regard, the prepared hybrid nanocatalyst was utilized in the synthesis of pharmaceutical components such as 2H-indazolo[2,1-b] phthalazine-triones (Fig. 32a) and benzo [4,5]imidazo [1,2-a] pyrimidine derivatives through multicomponent reactions (MCRs) under moderate and green reaction conditions (Fig. 32b). In addition to good catalytic reusability (8 times), for the synthesis of 2H-indazolo[2,1-b]phthalazine-triones, a high reaction yield (97%) in just 5 min at 90 C was obtained using only 20 g of the catalyst in a one-pot, three-component, solventfree reaction, which is an accomplishment compared to the time taken when the reaction was performed with neat NiFe 2 O 4 . Moreover, for the synthesis of benzo [4,5]imidazo[1,2-a]pyrimidine derivatives at 110 C under solvent-free conditions, 95% yield was obtained. Signicantly, phthalazine-trione derivatives are well-known heterocycles used in the pharmaceutical and biological elds including vaso-relaxants, 190 antifungal, 191 antimicrobial, 192 anti-cancer, 193 and anti-inammatory agents. 194 Besides, benzo [4,5]imidazo [1,2-a]pyrimidines are biologically related fused pyrimidine derivatives, which demonstrate highlighted therapeutic and biological characteristics such as antimicrobial, 195 anti-inammatory, 196 protein kinase inhibitor, 197 and anticancer. 198 In this report, a hybrid magnetic nanocomposite, ZnS/ CuFe 2 O 4 , was applied as a heterogeneous catalyst to synthesize 2,4,5-triaryl-1H-imidazole derivatives through the one-pot condensation of various aromatic aldehydes, benzyl and ammonium acetate, as depicted in Fig. 33. The imidazole nucleus acts as the leading scaffold to form signicant biological active molecules with antibacterial, antifungal, anti-inammation, anticancer, antiviral, anti-diabetic, anti-allergic, analgesic and herbicidal functionalities. 199,200 Some aromatic aldehydes were used in the synthesis of 2,4,5-triaryl-1H-imidazole derivatives. The aromatic aldehydes produced the desirable corresponding products in 82-92% yield due to their electron withdrawing and donating substituents.
Precisely, due to the synergistic effect of the active sites of alginic acid (several hydroxyl and carboxylic acid groups in its structure) and Lewis acid centers of ZnFe 2 O 4 , the hybrid catalyst demonstrated a remarkable yield of 93% in 10 min under the optimized conditions compared to its individual components. In the rst stage, the heterogeneous nanocatalyst activates the carbonyl groups of dimedone and aldehyde in two paths from a mechanistic view. The formation of a hydrogen bond results from the hydroxyl or carboxylic acid active groups in alginic acid as the organic constituent of the catalyst or Lewis acid centers of ZnFe 2 O 4 as the inorganic part. Then, the activated aldehyde and dimedone are exposed to catalytic Knoevenagel condensation to form molecule (5). Aerwards, the malononitrile as a C-H acid attacks the intermediate through Michael addition. In the next step, an intramolecular cyclization happens for molecule (5) to form intermediate (7). Eventually, the product formation is implemented by tautomerization of intermediate (7). The proposed mechanism is shown in Fig. 35.
The high reaction yield in the range of 83-95% for ten 2amino-3-cyano-4H-pyran derivatives should be highlighted to indicate the other strengths of this study. Also, a convenient purication procedure with high stability and reusability for ve sequential catalytic cycles was carried out. Notably, the 4Hpyran family and their derivatives are the main parts in the production of natural and chemical molecules. They exhibit extensive favorable pharmaceutical applications such as anticancer, diuretic, spasmolytic, antibacterial, anti-HIV, antimalarial, anti-inammatory, antihyperglycemic and dyslipidemia activities. 201,202 Besides, they have demonstrated therapeutic effects in some neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. 203 Also, a magnetic MOF catalyst, NiFe 2 O 4 @MOF-5, was applied as a heterogeneous catalyst to synthesize 2-substituted alkyl and aryl(indolyl) kojic acid derivatives through the solvent-free, onepot, three-component reaction of aldehyde, indole, and kojic acid. 83 Table 3 lists some of the magnetic catalytic systems that have been suitably utilized for the synthesis of pharmaceutical compounds under mild reaction conditions.

Magnetization in micro and nanoscale materials
Magnetic nanoparticles (MNPs) were studied over 50 years ago just based on the specic difference in their high surface-tovolume ratio to bulk materials. 224 Since then, impressive signs    Review Nanoscale Advances of the synthesis progress of MNPs have been seen regarding their sizes, shapes, compositions, and core-shell structures. 225 The sensitivity and efficiency of MNPs are directly related to their higher saturation magnetization (maximum magnetization possible). The effects of geometry and shape such as composition variation are pivotal factors in enhancing their magnetic properties. 226 Core-shell MNPs are dependent on the ligand and the surface interactions of nanoparticles, the effect of the relative thickness of their shell, and size of the coated nanoparticles. 227 Briey, the size, shape, composition and coreshell design in an appropriate synthesis are fundamentals of nano magnetization, which play vital roles in tuning the magnetic properties. Also, the intrinsic and extrinsic magnetic properties of materials should be considered. Atomic and molecular structure dene the magnetic dipole and net magnetization to determine the diamagnetic, paramagnetic, ferromagnetic, ferrimagnetic, and antiferromagnetic properties. 228,229 As can be seen in Fig. 36, the behavior of a material is entirely different due to the adjustment and response of its magnetic dipoles in the presence and absence of an external magnetic eld. 230 Superparamagnetic property has special importance because of drug delivery and MRI. Magnetic particles are referred to as superparamagnetic due to their magnetic properties upon the removal of an external eld.
The effect of temperature changes the behavior of ferromagnetic and ferrimagnetic nanoparticles if they are considered in the superparamagnetic category (Fig. 37). This is the case when the measuring time is longer than the relaxation time; however, when the measurement time is shorter than the relaxation time, the nanoparticles are in a "blocked" (ferromagnetic) regime. 230,231 where k B is the Boltzmann constant, K is an anisotropy constant, and V is the volume of one MNP. The magnetic anisotropy energy is the energy that retains the magnetic moment in a particular orientation. Eqn (1) shows that the blocking temperature (TB) increases quickly with particle size, which is pertinent for only small MNPs. The multi-domain, single-domain and superparamagnetic regimes exhibit more magnetic behavior if the MNP size becomes smaller. 230,232 If the MNP is synthesized below the critical volume/size, it tends to be a single magnetic domain structure, whereas if it is bigger than the critical volume, it tends to be multi-domain, and the optimized synthesized MNP tends to the superparamagnetic regime (Fig. 38). 230 The domain wall thickness depends on the exchange energy (which is the energy required to retain the spins parallel and is low when there is a thick wall), magnetization, and anisotropy of the nanoparticle. 233 We discussed the size of nanoparticles in the previous subsection regarding the relationship between nanoparticle size and magnetic properties, although there is another pivotal factor. The shape of nanoparticles plays a vital role in the differentiation of their magnetic properties. Nanorods, nanodiscs, nanowires, nanoowers and tetrapods are some different shapes that exhibit varying properties. CoFe 2 O 4 (cube and sphere) differs in coercivity, g Fe 2 O 3 (cube and sphere) differs in coercivity and higher TB, FePt (cube, octapod and cuboctahedron) differs in coercivity and TB, and Fe 3 O 4 (cube and sphere) differs in TB. 234 Researchers relate these differences to the less surface pinning according to fewer missing coordinating oxygen atoms. 235 In addition to the unique morphologygenerated gradient for the magnetic eld, a higher surfacearea-to-volume ratio is related to this variation, where more protons are present close to the magnetic eld. However, no conclusion favours a particular shape, although MNPs with at surfaces demonstrate promising biomedical applications to eliminate large aggregates in the body rather than gathering in the tumor. 236 Finally, we discuss the composition of MNPs for the specic magnetic characteristic determination that denes their main behavior. Precursor concentration, synthesis route, and the dopant character specically impact the magnetic properties of composites. 237 Varying the precursor ratio affect the coercivity and M s (emu g À1 ) and changes the magnetic properties. The cation distribution in the octahedral and tetrahedral sites, in addition to the nature of the cation itself, denes their proper replacement by dopants (Fig. 39). Cationic exchange is an applicable method to produce various structures for specic applications. 230,238 6. Reusability of micro and nanoscale magnetic catalytic systems One of the most signicant parameters of catalytic systems is their reusability, which affects their commercial applicability, suitability, and sustainability. Also, the reusability of catalysts plays a vital role in the catalytic oxidation process and impacts the cost of operation and catalyst separation in various applications. 239 Catalysts are introduced to optimize successive reaction cycles aer their recovery, rinsing, and drying to investigate their reusability. 159,[240][241][242] Magnetic catalysts have higher reusability due to their facile workup using only a magnet. In this case, due to the lower metal leaching, the catalytic efficiency increases. 243 Maleki et al. introduced a volcanic-based mesoporous magnetic catalytic system, pumice, with excellent reusability (six consecutive times), which authenticates the benecial industrial applications of this natural-based catalyst, as shown in Fig. 40. 244 It was proved that the experimental procedure increased the reusability of the catalyst. For example, the regeneration of magnetic nanoscale zero-valent iron (nZVI)@Ti 3 C 2 -based MXene nanosheets by treatment with dilute HCl demonstrated an optimal method to enhance their reusability. The surface inactivation of the nZVI particles (nZVIPs) was caused by the dense iron-based oxide layer covering the active sites, resulting in poor reusability. 245 A slight loss in activity is mainly attributed initially to the leaching of metal ions from the catalyst during the reaction, recovery, and washing steps, resulting in a loss of active sites. Secondly, some residual by-products on the catalysts may cause the active sites to be obstructed, reducing the degradation yield of organic pollutants. Moreover, in highly porous catalysts, pore blockage during the reaction is highly probable, leading to a decrease in catalytic activity. 172,246 Table 4 displays some magnetic catalytic systems with improved reusability.
Generally, in the scope of catalyst reusability, the chemical, physical, and mechanical stability of a catalysts should be monitored to accommodate industrial requirements and environmental considerations. From a mechanistic view, as long as the shape and structure of a magnetic catalyst are maintained, it means that it will display high structural strength in successive recovery cycles and is not degraded. 247 For instance, Boruah et al. introduced an ammonia-modied graphene sheet (AG) with Fe 3 O 4 MNPs decorated on its surface. This magnetic catalyst with the synergistic effect caused by amide-functionalized graphene and Fe 3 O 4 MNPs hamper the rate of electron-hole pair recombination, leading to recyclability for ten cycles, representing the high structural stability of the AG/ Fe 3 O 4 photocatalyst. Besides its enhanced stability and convenient separation, the high photocatalytic yield of this magnetic catalyst shows its potential for scaled-up applications. 248 Glutathione-coated gold magnetic nanoparticles Enhanced storage and reusability stability. Immobilized biocatalyst showed good stability aer ten repeated cycles Fe 3 O 4 anchored on reduced graphene oxide (rGO) through urushiol facile cross-linking (Fe 3 O 4 -U-rGO) exhibited a recycle stability of up to seven continuous cycles. One of the impressive factors affecting the structural stability is the urushiol molecule, which creates robust coordination to metal oxides and connects other materials via its structural phenolic hydroxyl groups. Due to the enhanced Fenton reactions of the Fe 3 O 4 -U-rGO magnetic composite, the generation of iron sludge and undesirable decomposition of H 2 O 2 to H 2 O and O 2 were inhibited. 249 Also, for acceptable catalytic performance, metal leaching as a factor affecting the stability of catalysts under harsh conditions such as acidic medium should be considered. The coherence, correlation, and overall physical properties of the structure should be maintained. 250 To investigate the catalyst activation aer recycling cycles, comparing the adsorptions bands in the FT-IR spectrum of the recovered catalyst and the original one seems necessary. 251 In this case, another work applied a heterogeneous magnetic catalyst, i.e., an immobilized polymeric sulfonated ionic liquid on core-shell-structured Fe 3 O 4 /SiO 2 composite (Fe 3 O 4 /SiO 2 -PIL), where the conversion of oil did not decrease signicantly aer ve cycles of reutilizing, displaying the favorable recyclability of the catalyst. The durable structural stability of the catalyst indicated a strong attachment between the active acidic species and Fe 3 O 4 /SiO 2 support. The reusability results veried a desirable heterogeneous catalyst from economic and environmental aspects compared to homogeneous catalysts, highlighting its applicability in the industrial production of biodiesel. 252 It can be claimed that a magnetic catalyst is chemically stable when the deconjugation and chemical structure alteration of its active sites do not happen. In the case of metal oxidebased catalysts, sonication is proposed as an efficient way to recover magnetic catalysts given that agglomeration may occur during the catalytic procedure. The combination of magnetite NPs, i.e., Fe 3 O 4 , and metal oxide NPs such as ZnO with a high agglomeration propensity can enhance the efficiency of the catalytic system through the adsorption of the target contaminants. The enhancement caused by magnetization correlates with the reduction in metal oxide agglomeration and catalytic performance improvement by the Fe 2+ active octahedral sites of Fe 3 O 4 reacting with H 2 O 2 molecules, resulting in the formation of cOH and HO 2 c radicals, which eventually enhances the reusability of sonocatalysts and metal oxides. 250 Besides, in ultrasound-assisted catalysis systems denoted as sonocatalysis, the activation of the sonocatalyst occurs under ultrasound irradiation, which accelerates the degradation rate via the production of extra reactive species. In this respect, many sonocatalysts, namely ZnO, TiO 2 -NiO, and TiO 2 , have been activated by ultrasound irradiation. [253][254][255] 7. Structural stability of micro and nanoscale magnetic catalytic systems Stability is one of the critical parameters affecting the performance of catalysts. Different factors can affect their stability, such as pH, 256 temperature, 239 and reaction conditions. As the temperature increases, the dye removal rate increases. Peroxymonosulfate catalyzed by reusable graphite felt/ferriferous oxide dissociated into sulfate and hydroxyl radicals via thermolytic division of its O-O bond.
Additionally, a higher temperature produces more free radicals. 239 Metal ion leaching is one reason that causes catalyst deactivation. In this case, the catalyst is immersed in aqueous solutions for a certain number of days. Subsequently, the leached metal concentration demonstrates the stability of the catalyst. 257 Besides, the agglomeration of NPs diminishes the catalytic activity and stability. 243 Magnetic nanoscale zero-valent iron (nZVI)@Ti 3 C 2 -based MXene nanosheets exhibited enhanced catalytic reactivity and stability due to its synergistic effect. Specically, the Ti 3 C 2 -based MXene prevents the agglomeration of the nZVI particles (nZVIPs) and enhances the electron transition between the magnetic particles with a diameter of 10-40 nm. 245 Different analyses are used to explore the structural stability of catalysts. Fig. 41a-c show the FT-IR, EDS, and SEM analyses of recovered magnetic pumice catalysts aer six successive recycling cycles. The peaks at 580, 950, 1000, and 3390 cm À1 correspond to the characteristic peaks of the catalyst. Two new peaks emerged at 3600 cm À1 , which are related to the ALO-H bonds in the internal alumina network and prove the presence of voids in pumice aer complete rinsing. The EDS analysis did not display any changes in the structural elements of the recovered catalyst. Eventually, according to the SEM images, the structure, morphology, dispersion, and uniformity of the heterogeneous catalyst remained unchanged even aer six recycling cycles. 244

Turnover number (TON) and turnover frequency (TOF)
The turnover frequency (TOF) rst widened into the scope of heterogeneous catalysis according to Boudart's denition, as follows: "Certainly, the catalytic activity, must be assigned to the exposed number of surface atoms of a determined kind. Thus, to put catalytic activity in words, it is a turnover number equal to the number of reactant molecules converted per minute per catalytic site for specied reaction conditions". 264 Also, the authentic IUPAC Gold Book denes the turnover frequency term as: "Commonly called the turnover number, N, and determined, as in enzyme catalysis, as molecules that react per active site in unit time". 265 TOF, turnover frequency (TOF ¼ (yield/time)/ amount of catalyst (mol)). TON, turnover number (TON ¼ yield/amount of catalyst (mol)). 266 Alternatively, to evaluate intrinsic properties such as catalytic efficiency and recycling factors, TOF and TON are two signicant parameters. The TON is determined as the number of molecules that experience transformation by ratio of active sites to products in the presence of 1 g catalyst. Also, the TOF is calculated as TON/ degradation time. 267 Numerous methods that mainly utilize homogeneous metal complexes and heterogeneous systems for the hydration of nitriles have been reported. Alumina, potassium uoride-doped Al 2 O 3 and phosphates, silica-supported manganese oxides, modied hydroxyapatite, and ruthenium hydroxide coated on alumina and ferrites are examples of heterogeneous systems.
Nonetheless, due to their deciency, laboriousness product and catalyst separation, requirement of inert atmosphere to conduct reactions for air-sensitive metal catalysts, poor catalyst reusability, very low TONs were obtained. 268 In hydrogenation reactions of alkynes or alkenes, catalysts such as noble metals NPs represent high turnover numbers (TONs). 269 Hamishehkar et al. synthesized glutathione-decorated gold-magnetic NPs (GSH-AuMNPs) as a competent recyclable catalyst. To express intrinsic activity, the TOF was concluded to be 12.5 h À1 . This catalyst with high catalytic activity is a good candidate for biomedical and pharmaceutical applications. 270 Koukabi et al. designed an air-and moisture-stable poly(2--acrylamido-2-methyl-1-propane sulfonic acid)-stabilized magnetic palladium catalyst with a core-shell structure. This catalyst was applied in Suzuki-Miyaura and Mizoroki-Heck reactions to produce coupling products with TON and TOF values of 14 143 and 4900 and 28 296 and 7424, respectively. 271

Multifunctional micro and nanoscale magnetic catalytic systems
A wide variety of multifunctional systems based on magnetic nanoparticles (MNPs) and derivative nanocomposites has amazed scientists because of their manifold applications using one material. These materials are used in various elds, such as sensing, adsorption, medicine, energy, and electronics. Recently, Yang et al. synthesized a 3D coral-like layered porous magnetic eggshell membrane (ESM)/CuFe 2 O 4 nanocomposite through a green and affordable route from useless materials, exhibiting multifunctional applications including adsorption, catalysis, and antibacterial properties in water treatment against Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). The maximum adsorption capacity of Congo red (CR) was evaluated to be 199.23 mg g À1 . Further, the catalytic activity of 4-nitrophenol reduction using this magnetic nanocomposite was high, and the attained degradation rate was 98.9% in 5.5 min. 272 Besides, multifunctional magnetic NiFe 2 O 4 @TiO 2 /Pt nanocomposites were prepared through the sol-gel procedure. In this work, the high performance of rapid photo-degradation of two azo dyes as water pollutants under UV-vis light, together with antibacterial activity against Escherichia coli (E. coli) bacteria were demonstrated. 273   were liquid (pyrolytic fuel), gas (combustion gas), and char (activated carbon via gasication procedure). These products conrm the generation of valuable materials from waste. This nanocomposite acted as an adsorbent for mercury(II) elimination from sewage, which corresponded to the Langmuir isotherm with a maximum adsorption capacity of 1250 mg g À1 . 275 Another study focused on an approach for the one-pot synthesis of a CoNi alloy-reduced graphene oxide ((CoNi D ) 60 -RGO 40 ) multifunctional nanocomposite, which acted as a remarkable catalyst for the 4-nitrophenol reduction reaction with its k app value determined to be 20.55 Â 10 À3 s À1 and 80-93% yield in the Knoevenagel condensation reaction. The easy separation of this magnetic nanocomposite and perfect performance of the recycled catalyst were noticeable. Also, this snowake-like dendritic nanocomposite operated as an active electrode in supercapacitors. The high performance of this supercapacitor was exhibited by its specic capacitance of 501 F g À1 (at 6 A g À1 ) and energy density of 21.08 W h kg À1 at a power density of 1650 W kg À1 . The synthesis of the snowake-like dendritic (CoNi D ) 60 RGO 40 nanocomposite and its catalytic and supercapacitor applications were presented in this study. 276 Multifunctional and stimuli-responsive MNP-and derivative nanocomposite-based systems have emerged from nanobiotechnology with signicant impacts on drug delivery, cancer diagnosis and treatment. These systems overcome the limitations of conventional therapeutic methods for cancer in recent decades. Among them, Fe 3 O 4 MNPs have attracted attention from scientists due to their innate magnetic resonance imaging (MRI), drug delivery, biocatalytic activity, magnetic hyperthermia treatment (MHT), and stimuli-responsive therapy for multimodal approaches. The size and morphology are factors that determine the properties of these MNPs. There are three main routes presented for the synthesis of Fe 3 O 4 MNPs, including physical, biosynthetic, and chemical approaches. Physical synthesis is a method that cannot entirely direct the size to the nano-scale. The biosynthetic process faces shortcomings of long synthesis time, low yield reaction, and broad size distribution. Thus, to overcome these disadvantages, chemical synthesis tends to be employed with superiorities such as facile procedure, low cost, high yield, and monodispersed MNPs. The various applications of Fe 3 O 4 MNPs and their chemical synthetic strategies are presented in Fig. 42. 277 To better interact with biological media, surface-modied Fe 3 O 4 MNPs with good biocompatibility, high stability, and stimuli responsiveness are applied in magnetic nanoscale systems. Ligand substitution and encapsulation are strategic processes. An interchange between the intrinsic surface hydrophobic ligands of MNPs and hydrophilic ligands take place to aid in their dispersity in the biological environment. However, although this process retains the initial hydrodynamic size of the MNPs, it causes metal atom leakage and surface aws. Thus, the encapsulation/self-assembly process is employed to protect MNPs and to maintain their physical and  Fig. 43. 278 Feng et al. introduced poly(lactic-co-glycolic acid) (PLGA) drug-loaded magnetic Janus particles (DMJPs) as a multifunctional nanoscale system. In these three-sectioned Janus particles, Fe 3 O 4 MNPs effectively released paclitaxel anticancer drugs with the assistance of an external magnetic eld. 279 Another theranostic nanosystem is multifunctional gold MNPs. According to their nanoscale and inimitable physicochemical properties, they display thriving multimodal imaging and cancer treatment applications. Also, from the biosafety perspective of Au MNPs, several types of studies proved their low toxicity in biomedical applications. 280 Multifunctional catalytic systems are supplementary systems that improve the catalytic activity through the interaction of more than one catalyst functionality. 281 A chitosan/ionic liquid multifunctional catalyst was prepared with high catalytic activity and selectivity for the synthesis of dimethyl carbonates (DMC) due to its nucleophilic sites such as hydroxyl and amine groups and also absorption sites for CO 2 . 282 Additionally, magnetic multifunctional catalytic systems are benecial due to their ease of separation using a permanent external magnet to recycle the catalysts. According to the desirable conversion and selectivity of multifunctional catalysts applied in the green oxidation method of benzyl alcohol, Ye et al. introduced Pd/ Fe 3 O 4 @mCeO 2 yolk-shell microspheres, as presented in Fig. 44. The catalyst exhibited a good performance of 80.5% conversion of benzyl alcohol and benzaldehyde selectivity of 94.8%. 283 In another study, NiFe-NiFe 2 O 4 was synthesized via the solution blow spinning (SBS) method, which exhibited good electrocatalytic activity in the oxygen evolution reaction (OER) with a noteworthy turnover frequency (TOF) of 4.03 s À1 . 284 Another electrocatalyst for the OER and also water splitting, resulting in the production of pure H 2 , is cobalt ferrite (CoFe 2 O 4 ) powder obtained using agar-agar from Rhodophyta. The TOF of this electrocatalyst was 8.8 Â 10 À2 s À1 . 285 Also,  Nagashri et al. prepared a cost-effective copper(II) complex with a 1,10-phenanthroline derivative catalyst for H 2 evolution as a fuel with a TON and TOF of 15 600 and 8100, respectively. 286 Moreover, multifunctional catalytic systems present a satisfactory performance in the Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions. In this regard, the oxygen insensitive and phosphine-free MNP/HPG-CA/Pd catalyst with a turnover frequency of 372 h À1 was effortlessly recovered and reused many times. 287 Similarly, a one-pot hydrothermal-synthesized Pd-Fe 3 O 4 /rGO nanocomposite with a TOF of up to 1449 h À1 was applied in C-C coupling reactions. 288 Magnetic core-shell-structured multifunctional heterogeneous catalysts exhibit synergistic effects from each constituent, such as preferable magnetic properties, catalytic activity, and structural stability. A layer-by-layer assembled Fe 3 O 4 @PDA-Pd@[Cu 3 (BTC) 2 ] nanocomposite was employed for the reduction of 4-nitrophenol and Suzuki-Miyaura cross-coupling reactions. 77 Table 5 summarizes the information of some magnetic catalytic systems that exhibit versatility in chemical reactions.

Conclusion and future outlook
In this survey, a brief overview of the recent advancements in magnetic micro-and nanoscale catalytic systems was presented. Concurrently, their myriad of benets and convenience, such as facile recovery and high chemical and structural stability, in the degradation and synthesis of assorted pharmaceutical compounds was discussed. Herein, the structure and properties of magnetic catalytic systems were classied, and all the recent accomplishments by researchers were briey implied in this context. Furthermore, the synergistic effects between organic and inorganic catalysts as hybrid micro-and nanoscale magnetic composites were considered. In general, magnetic catalytic systems are developing rapidly. In this regard, researchers are trying to optimize previous processes both in terms of cost and time, as well as in terms of improving catalytic structures. Alternatively, it is imperative to focus on environmentally friendly structures and extracted materials from nature. These materials do not harm the environment, and are considered an opportunity in terms of mass production and industrial use.
As a path to the future, attention to porous structures and frameworks is a priority. Due to their high porosity, these structures can act as reaction reactors and accelerate catalytic processes. These structures include metal-organic frameworks (MOFs) as well as a newer category, covalent organic frameworks (COFs). In addition to high porosity, COFs can also host magnetic nanoparticles, which aid the convenient separation of catalysts. Moreover, the prominent features of these frameworks are their lower density than MOFs and their high stability under acidic, alkaline, and redox conditions. Besides, attention should be given to magnetic heterostructures, which possess features beyond their single components, resulting in various applications in biomedicine and catalyst scopes. The insight into the reaction parameters, including ligands and counter anions, leads to the application of magnetic heterostructures in the desired elds. Regarding the biomedical application of magnetic heterostructures, the requirement of their long-term appraisal in terms of biotoxicity and metabolism of the magnetic heterostructures seems vital, while in terms of catalytic applications, stability enhancement has been highlighted as the major issue. 299 Alternatively, the preparation approach of metal complexes containing immobilized MNPs enables phase tunability of the magnetic oxides applying a single path (Fe 3 O 4 , g-Fe 2 O 3 , and a-Fe 2 O 3 ). Even though the immobilization of MNPs on metal complexes results in higher activity and selectivity in the catalytic systems, the hydrophobicity may affect their catalytic performance. However, silica-and carbon-coated MNPs can prevent the aggregation of MNPs, providing functional groups to immobilize their active catalytic sites. 300 Magnetic biochar is another magnetic catalytic system originating from a wide range of sources, which can be prepared via various routes and employed in the catalytic degradation of dyes, antibiotics, herbicides, and other organic contaminants. Although MBC catalysts exhibit the benets of excellent stability, good reusability, and acceptable organic pollutant degradation yield, insight into many related facets to the mechanism of MBC is scarce. For instance, more environmental considerations in the case of metal leaching of some metal-loaded MBCs, profound Review Nanoscale Advances studies on the routes for the regeneration of MBC catalysts, and concise research on the incomplete mineralization of degraded contaminants should be undertaken. 38 Finally, the use of hybrid composites also requires more attention due to the catalytic benets of both organic and inorganic compounds. Table 6 lists the abbreviations used herein and their full denitions.

Conflicts of interest
There are no conicts of interest to declare.