Green dual-action potential of newly synthesized sulfonamide-based ionic liquids: larvicidal activity against Culex pipiens and purification of oil-polluted water

Abstract

The discovery of novel ionic liquids incorporating a sulfonamide moiety has attracted significant attention owing to their unique bioactive properties and versatile applications. The present study focuses on the design, spectroscopic characterization, and evaluation of the petroleum-dispersing and insecticidal activities of seven newly synthesized compounds (4a–e, 5c, and 5e). The synthesized ionic liquid compounds were successfully characterized by spectroscopic methods. Their efficiency in dispersing or collecting thin films of petroleum was evaluated in various water systems. Notably, most of the compounds, especially 4d, demonstrated strong capabilities in removing petroleum films from water. Additionally, the larvicidal activity of the compounds was evaluated against Culex pipiens, one of the most hazardous mosquito vectors. Among them, compounds 4d, 4b, and 5e exhibited significant potency, with LC₅₀ values of 161.03, 207.82, and 229.72 ppm, respectively. These compounds were found to be more effective than 5c, showing 3.07-, 2.38-, and 2.15-fold higher activity. In conclusion, the synthesized compounds demonstrated a dual functionality: efficiently dispersing or collecting oil films from water while also exhibiting larvicidal activity against aquatic Culex pipiens larvae, with compound 4d showing the highest efficacy. Hence, these compounds hold promise for application in both water purification and mosquito control.

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1. Introduction

Ionic liquids (ILs) are salts that have a melting point below 100 °C¹ and are formed from anions and cations, such as pyridine, imidazole, and other organic or inorganic cations. Because of their enhanced properties over conventional solvents, ILs have been described as new “green solvents” that will eventually replace organic solvents, such as outstanding solubility in inorganic, organic, low melting point, easy recovery, high stability, and polymer materials, almost no vapor pressure, etc.^2–4 Because of their unique physical and chemical characteristics, ILs are utilized extensively in various industries, including organic synthesis,^6,7 food processing,⁵ electrochemistry,^8,9 and biocatalysis.^10–14 In the past decade, the scientific community has focused a lot of attention on the potential uses of ILs in the development of creative, effective antiseptics, disinfectants, insecticides, and antiviral medication.^15–19

Mosquitoes are the most dangerous vector, transmitting various infectious diseases. Culex pipiens causes a variety of infections, such as lymphatic filariasis, Japanese encephalitis, West Nile fever, and Sindbis fever.²⁰ Females of C. pipiens are blood feeders on humans and birds and hence transmit infectious diseases to them.²¹ Most of these infectious diseases aren't vaccine-preventable in humans.²² Therefore, mosquito control remains an indispensable tool in the prevention of mosquito-borne infections.

Vector management strategies have traditionally relied on killing mosquito aquatic stages, larvae, using many insecticides, including chemical larvicides.²³ Larvicides are applied in the breeding habitat to target larvae before maturation into adult mosquitoes. Therefore, the larvicidal application in breeding aquatic habitats reduces the emergence of adult mosquitoes in nearby areas.²⁴ Temephos, O,O,O′,O′-tetramethyl O,O′-thiodi-p-phenylene bis(phosphorothioate), is an organophosphate recommended larvicide by WHO used for the control of various vectors of diseases.²⁵ Aggressive application of chemical insecticides in mosquito control programs which have negative effects on the environment and human health.²⁶ In addition, the buildup of insecticide resistance among mosquito vectors became widespread.²⁷ Consequently, novel compounds with new characteristics are needed to reduce disease transmission. The water solubility of insecticides appears to impact their efficacy. Although it might not have enough residual activity (persistence) over a long period, they don't harm non-target organisms and the environment, and don't develop insecticide resistance.

Sulfonamides are a broad class of bioactive substances that include antiviral, anticancer, insecticidal, and antibacterial activities.^28,29 Temephos as a class of sulfonamides (A, Fig. 1) has long been employed as a larvicide in many countries worldwide. It disrupts the mosquito life cycle by targeting the larval stage and acts through a cholinergic pathway common to both insects and mammals, resulting in neurotoxic effects.³⁰ A sulfonamide-incorporating quaternary ammonium iodide derivative (B, Fig. 1) gave good larvicidal activity against C. pipiens with potent activity (LC₅₀ = 26.71 ppm).³¹ Also, a cationic surfactant–sulfonamide conjugate (C, Fig. 1) showed high activity toward B. subtilis and E. coli, with values comparable to the evaluated reference drugs.³² Against Mythimna separata Walker, a derivative of propargyloxy-substituted benzenesulfonamide (D, Fig. 1) has shown great insecticidal action. The isothermal titration calorimetry results show a substantial interaction between subunit H of compound D with the ATPase enzyme and show highly significant activity with a lower LD₅₀ value (28.0 µg g⁻¹) than celangulin (344.0 µg g⁻¹).³³ Various p-twerelsulfonamide (E) derivatives containing alkyl N-substituents were found to have a favorable inhibitory effect against the CA IX enzyme with an IC₅₀ of 94 nM.³⁴ Aliphatic sulfonamido-quaternary ammonium salts (F, G) caused apoptosis by upregulating RhoB.^35,36

Fig. 1 Some bioactive sulfonamides, sulfonamido-quaternary ammonium salts and temephos.

One of the major issues facing the world is the pollution of water surfaces with petroleum. A significant amount of petroleum oil enters the hydrosphere for various reasons, such as accidents involving oil tankers and pipelines. While the thin petroleum layer remains environmentally dangerous, the mechanical procedures can separate the thick petroleum film. To address this particular problem, various techniques were used, such as colloid-chemical techniques, which involved applying petro-collecting and dispersing agents to remove such thin oil layers.^37–39

Ionic Liquids and ionic liquid-based surfactants, particularly gemini and conventional cationic surfactants, are the most effective methods to clean the water surface by dispersing and/or collecting compounds that form thin petroleum films during oil processing stages.^40–44

The rationale of this study is that the design compounds of four moieties: aromatic sulfonamide moieties, quaternary ammonium groups, long polymethylene ether chain and chloride/tetrafluoroborate. The aromatic sulfonamide moieties (Ar–SO₂–NH–) have strong enzyme inhibition, targeting insect physiological pathways. Quaternary ammonium groups are a permanent positive charge, enhancing interaction with nucleophilic enzymes or receptors for better binding and inhibition. The long polymethylene ether chain enhances membrane permeability and solubility, aiding compound translocation into insect cells. These designed compounds contain an amphiphilic structure with a long polymethylene ether chain, which is a flexible hydrophobic tail that combines with oil. Moreover, these amphiphilic molecules reduce surface tension, helping break oil into smaller droplets (dispersing) or gather droplets together (collecting). The positively charged quaternary ammonium head is hydrophilic, allowing good interaction with water, which interacts electrostatically with negatively charged particles in oil, enhancing aggregation or dispersion. Replacing chloride with tetrafluoroborate (BF₄⁻) in the compounds enhances chemical stability and may reduce toxicity to non-target organisms.

The current work aims to prepare several sulfonamido-quaternary diammonium iodides with dual function, purifying water from thin films of oil and reducing the aquatic stage of the dreadful disease vector (larvae of C. pipiens). Hence, their petro-collecting/dispersing indices in the diluted and undiluted form on the water surface with various degrees of mineralization were investigated. Furthermore, their larvicidal effectiveness against C. pipiens larvae was assessed.

2. Experimental

2.1. Materials and reagents

2.1.1. Reagents. All utilized solvents and chemicals were used without further purification. Sinopharm Chemical Reagent Co., Ltd. was the supplier of 4-methylbenzenesulfonyl chloride (99.0%) and 4-cyanobenzenesulfonyl chloride (≥98.0%). Naphthalene-2-sulfonyl chloride (99.0%) and thiophene-2-sulfonyl chloride (96.0%) were from Shanghai Macklin Biochemical Co., Ltd., and 2,4,6-triisopropylbenzenesulfonyl chloride (97.0%) and 4-(tert-butyl)benzenesulfonyl chloride (98.0%) were from Alfa Aesar China Co. Ltd. (Shanghai, China). Sinopharm Chemical Reagent Co. Ltd. was also the supplier of p-toluenesulphonic acid (PTSA), tetrahydrofuran (THF, ≥99.0%), ethyl acetate (≥99.6%), sodium tetrafluoroborate (NaBF₄), dichloromethane (DCM, 99.5%), ethanol (≥99.5%), methanol, petroleum ether (60–90 °C, >99.7%), and diethyl ether.

2.1.2. Synthesis of ILs (4a–e, 5c and 5e).
General preparation of hexane-1,6-diyl bis(2-chloroacetate) (3). In the presence of PTSA (1 mol%), in dry toluene, the appropriate 1,6-hexanediol (2a–c, 1 equiv.) was mixed with chloroacetic acid (1.3 equiv.). After that, Dean–Stark equipped the mixed solutions and refluxed them at 135 °C while stirring until an equivalent amount of water formed. The alkanes bis(2-chloroacetate) (3a–c) were created and removed by extraction using n-hexane, followed by drying over anhydrous Na₂SO₄, evaporating the solvent, and then vacuum-drying to produce the desired product with a 94% yield.
Hexane-1,6-diyl bis(2-chloroacetate) (3). Colorless viscous with yield = 94%. FT-IR (ATR) ν/cm⁻¹; bands at 2956 for νCH aliphatic chain, 1753 for C=O ester, 1476 for CH₂ bending, 1170 for C–O ester (Fig. S1).
Procedure for producing sulfonamide derivatives, 2a–e. 3-(N,N-Dimethylamino)-1-propylamine (1.14 g, 11.30 mmol) and Et₃N (43.02 g, 14.15 mmol) in 60 mL of CH₂Cl₂ were mixed with sulfonyl chloride derivatives (1a–e, 5.65 mmol) across several portions. After the addition was finished, the resulting solution mixture was stirred for ten hours. Following treatment with a 50 mL half-saturated sodium chloride solution, the mixture was extracted three times using 50 mL of CH₂Cl₂. After drying the organic layer over anhydrous Na₂SO₄, the solvent was filtered, evaporated, and extracted using a high vacuum. Flash chromatography (SiO₂, CHCl₃ : MeOH, 5 : 1) was used to purify the crude product, yielding 2a–i with a range of 91–95% as white to yellow solids. All spectroscopic analysis and method of preparation were reported via our previous work.⁴⁹
Quaternization process of sulfonamide derivatives (2a–e) with hexane-1,6-diyl bis(2-chloroacetate) (3). In five round-bottom flasks, solutions of sulfonamide derivatives (2a–e, 5 mmol) in 20 mL acetonitrile were prepared separately. Next, the previously generated solutions were mixed with 20 mL of acetonitrile to dissolve 10 mmol of hexane-1,6-diyl bis(2-chloroacetate). For around twenty-four hours, the mixtures are refluxed at 70 °C. Following the completion of the reaction and evaporation of the solvent, the residual materials were cleaned three times using diethyl ether in order to eliminate the unreacted components and purify the final compounds. The products' yields range from 88 to 90% with various colors and shapes.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(3-(4-cyanophenylsulfonamido)-N,N-dimethylpropan-1-aminium)chloride (4a). Yellowish white, mp = 72–75 °C yield = 88%. FT-IR (ATR) ν/cm⁻¹; 3321–3273 (νNH stretching), 3091 (νCH aromatic), 2851–2975 (νCH aliphatic fatty chain), 2231 (νC≡N, cyano group), 1741 (νC=O ester), 1632 (νC=N), 1451 (νCH₂ bending), 1154 (νC–O ester). ¹H NMR (400 MHz, DMSO-d₆) δ 8.46 (t, J = 5.7 Hz, 2H), 8.11 (d, J = 8.2 Hz, 4H), 8.01 (d, J = 8.3 Hz, 4H), 4.52 (s, 4H), 3.77 (s, 6H), 3.62–3.52 (m, 6H), 3.21 (s, 12H), 2.83 (d, J = 5.8 Hz, 4H), 1.95–1.82 (m, 4H), 1.46–1.34 (m, 4H), 1.34–1.23 (m, 4H). ¹³C NMR (101 MHz, DMSO-d₆) δ 165.71, 144.58, 133.98, 127.85, 118.10, 115.58, 62.61, 61.33, 53.49, 51.58, 33.01, 25.87, 23.15.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(thiophene-2-sulfonamido)propan-1-aminium) chloride (4b). Viscus yellow, yield = 90%. FT-IR (ATR) ν/cm⁻¹; 3369–3275 (νNH stretching), 3091 (νCH aromatic), 2845–2971 (νCH aliphatic chain), 1745 (νC=O ester), 1641 (νC=N), 1451 (νCH₂ bending), 1152 (νC–O ester). ¹H NMR (400 MHz, DMSO-d₆) δ 8.22 (t, J = 5.5 Hz, 2H), 7.96 (d, J = 4.9 Hz, 2H), 7.64 (d, J = 3.2 Hz, 2H), 7.27–7.17 (m, 2H), 4.54 (s, 4H), 3.76 (s, 4H), 3.58 (dd, J = 7.6, 4.4 Hz, 4H), 3.23 (s, 12H), 2.88 (d, J = 6.0 Hz, 4H), 1.95–1.85 (m, 4H), 1.47–1.35 (m, 4H), 1.29 (ddd, J = 18.3, 6.8, 3.6 Hz, 4H). ¹³C NMR (101 MHz, DMSO-d₆) δ 165.34, 140.78, 132.82, 131.91, 128.03, 62.34, 60.85, 53.00, 51.28, 32.67, 32.41, 27.94, 25.54, 25.25, 25.21, 22.49.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(naphthalene-1-sulfonamido)propan-1-aminium)chloride (4c). Yellowish white viscus, yield = 88%. ¹H NMR (400 MHz, DMSO-d₆) δ 8.47 (s, 2H), 8.23–8.12 (m, 6H), 8.06 (d, J = 7.7 Hz, 2H), 7.92–7.84 (m, 2H), 7.69 (t, J = 7.9 Hz, 4H), 4.55 (d, J = 15.5 Hz, 4H), 4.16 (t, J = 6.4 Hz, 4H), 3.66–3.52 (m, 4H), 3.22 (d, J = 3.9 Hz, 12H), 2.90–2.74 (m, 4H), 1.91 (s, 4H), 1.61 (s, 4H), 1.38–1.24 (m, 4H). ¹³C NMR (151 MHz, DMSO-d₆) δ 164.92, 136.89, 134.68, 132.16, 129.35, 129.17, 128.58, 128.28, 127.89, 127.46, 122.43, 72.52, 64.85, 58.85, 45.88, 43.29, 37.02, 29.83, 23.84.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(2,4,6-triisopropylphenylsulfonamido)propan-1-aminium)chloride (4d). White solid, mp = 80–82 °C, yield = 87%. ¹H NMR (400 MHz, DMSO-d₆) δ 7.71 (dd, J = 15.7, 5.9 Hz, 2H), 7.24 (d, J = 2.8 Hz, 4H), 4.67–4.34 (m, 4H), 4.15–4.07 (m, 4H), 3.75 (s, 4H), 3.57–3.45 (m, 4H), 3.23 (s, 12H), 2.98–2.83 (m, 6H), 1.88 (dd, J = 33.3, 6.9 Hz, 4H), 1.45–1.30 (m, 4H), 1.26 (dd, J = 13.2, 9.6 Hz, 4H), 1.20 (d, J = 5.1 Hz, 36H). ¹³C NMR (151 MHz, DMSO-d₆) δ 166.44, 151.97, 148.92, 130.92, 122.02, 69.76, 66.08, 62.40, 58.02, 44.91, 41.88, 33.92, 29.03, 24.54, 24.05, 22.03.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(4-methylphenylsulfonamido)propan-1-aminium)chloride (4e). White semisolid, yield = 89%. ¹H NMR (400 MHz, DMSO-d₆) δ 8.48 (d, J = 5.5 Hz, 2H), 8.11 (d, J = 8.2 Hz, 4H), 8.01 (d, J = 8.3 Hz, 4H), 4.52 (s, 4H), 3.77 (s, 6H), 3.61–3.49 (m, 6H), 3.22 (s, 12H), 2.84 (d, J = 11.6 Hz, 4H), 2.68 (s, 6H), 1.87 (t, J = 18.4 Hz, 4H), 1.48–1.34 (m, 4H), 1.27 (t, J = 10.8 Hz, 4H). ¹³C NMR (101 MHz, DMSO-d₆) δ 165.25, 143.90, 133.53, 128.25, 124.34, 62.61, 61.07, 53.92, 50.70, 32.32, 28.64, 26.10, 22.68.
Preparation of N,N′-((hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(naphthalene-1-sulfonamido)propan-1-aminium)tetrafluoroborate (5c) and N,N′-((hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(4-methylphenylsulfonamido)propan-1-aminium)tetrafluoroborate (5e). Using a specific amount of acetone as a solvent, 1 g (0.001 mol) of compounds 4c and 4e were added individually to a single-mouth flask together with 0.23 g (0.0021 mol) of NaBF₄ for 10 hours at 40 °C while being vigorously stirred. Filtration and vacuum distillation (at 60 °C and 450 mm Hg) were performed on the reaction mixture. After adding dichloromethane to the [4e]Cl and NaBF₄ residual, white particles precipitated. Thereafter, filtering was used to separate the solid precipitate. Lastly, the product was vacuum-dried for two hours at 80 °C in an oven to eliminate any remaining dichloromethane.⁴⁸ The typical synthesis route of [5e]BF₄ is shown in Scheme 1.

Scheme 1 A schematic pathway for the synthesis of sulfonamide-tethering cationic ionic liquids.

N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(naphthalene-1-sulfonamido)propan-1-aminium)tetrafluoroborate (5c). Yellowish white viscus, yield = 91%. FT-IR (ATR) ν/cm⁻¹; 3374 (νNH stretching), 3091 (νCH aromatic), 2845–2971 (νCH aliphatic chain), 1743 (νC=O ester), 1635 (νC=N), 1475 (νCH₂ bending), 1372 (S=O (sulfonyl) symmetric component), 1204 (S=O asymmetric stretch (sulfonyl)), 1194 (C–O stretch, νC–O ester). ¹⁹F NMR (565 MHz, DMSO-d₆) δ −74.52.
N,N′-((Hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl))bis(N,N-dimethyl-3-(4-methylphenylsulfonamido)propan-1-aminium)tetrafluoroborate (5e). White viscus, yield 93%. FT-IR (ATR) ν/cm⁻¹; 3373 (νNH stretching), 3067 (νCH aromatic), 2932 (νCH aliphatic chain), 1745 (νC=O ester), 1629 (νC=N), 1468 (νCH₂ bending), 1319 (S=O (sulfonyl) symmetric component), 1217 (S=O asymmetric stretch (sulfonyl)), 1135 (C–O stretch, νC–O ester). ¹⁹F NMR (565 MHz, DMSO-d₆) δ −61.21.

2.2. Methods of ILs characterization

2.2.1. Instrumentals. Thermo Scientific Nicolet iS10 FT-IR spectrometers were utilized to get the FT-IR spectra of every synthetic compound. Via tetramethylsilane (TMS) as the internal standard, Bruker Avance 400 MHz was used to collect NMR spectra, including ¹H and ¹³C NMR, in DMSO-d₆ solutions.

2.3. Collecting and dispersing of petroleum capacities

The new series of 4a–e, 5c, and 5e were found to be water soluble. We investigated their ability to disperse and collect petroleum films in two forms (2.5% aqueous solution and solid) on the water surface with various degrees of saltiness. The crude petroleum oil, which had a density of 0.85 g cm⁻³ and a viscosity of 0.17 cm² s¹ at 293 K, was extracted from the Red Sea of South Sinai, Egypt. The thin layer of crude oil (about 0.14 mm thick) on the water's surface with varying salinities was covered with 0.01 g of each produced compound or a 2.5% aqueous solution of the synthesized compound. Petro-collecting behavior (K) was calculated using the formula K = S_o/S, where S_o is the surface area of the petroleum film at the start of the experiment and S is the surface area of the petroleum spot produced by the action of the synthesized compounds. The surface area of the film was routinely measured during the monitoring procedure, and K values were computed at predetermined intervals (τ). The ratio of the surface area of clean water to the initial area of petroleum film is known as K_D (petroleum-dispersing ability).

2.4. Larvicidal activity against Culex pipiens larvae

2.4.1. Mosquito rearing. The larvae of C. pipiens were obtained from a stock colony that was reared in our insectary for several generations without exposure to any chemicals. The larval stage was maintained in a glass jar containing 500 mL of distilled water at a controlled photoperiod of 14 : 10 (L : D) and a temperature of 25–28 °C.⁴⁵ The larvae were fed on a mixture of dried yeast and biscuit (25 : 75 by weight). The emerged pupae are transferred in screened cages (25 × 25 × 25 cm³) for adult emergence. Adults were supplied with a glucose solution (10%), and females only fed on a periodic time. The laid egg rafts were transferred daily for stock-rearing plates.

2.4.2. Larvicidal bioassay. The synthesized compounds were tested at various concentrations on third-instar larvae of C. pipiens to evaluate their toxic effects on mosquito larvae, as referenced in 46. Five concentrations of tested compounds were prepared by dissolving them in distilled water to produce 80 mL of the final solution (100, 200, 400, 600, and 800 ppm) in a 100 mL jar. In the same manner, temephos, larvicide recommended by WHO (50% EC, LARVIGUARD®, Shri Ram Agro Chemicals, India) was dissolved in water to obtain the concentrations (50, 100, 200, 300 and 400 ppm). The test was performed using three replicates, each containing 20 newly educated third instar larvae. In the control series, only 80 mL of distilled water was used. After 48 h of exposure, the mortality was estimated.²⁴

2.4.3. Statistical analysis. The mortality percentage of various concentrations was recorded, and toxicity data were estimated by probit analysis.⁴⁷ The LDP line software calculated LC₅₀ and LC₉₀ with 95% confidence limits, along with the slope of the different concentrations and their mortality lines.

3. Results and discussion

3.1. Synthesis

Creating compounds containing a unique activity against a variety of targets is simple with a hybrid method. Depending on the application, a single-functionalized molecule can only effectively target one destination. In certain situations, or issues, these molecules won't be the best options. The development of compounds with two or more functionalities (conjugates or hybrids) will increase the range of applications for which they can be used, ultimately influencing several targets.

Ionic liquids incorporating sulphonamide groups have been used as antifungal and antibacterial agents. In the present work, we designed a novel ionic liquid bearing two ammonium salt moieties conjugated with different heteroaryl/aryl sulphonamides through a hexane spacer to synthesize ionic liquid–sulphonamide conjugates (4a–d, 5c, 5e) for multiple applications. In the synthetic strategy, N-substituted sulphonamides (2a–e) are first created by dehydrochlorinating sulphonyl chloride moieties (2a–e) with N,N-dimethylpropyl-1,3-diamine in dichloromethane under the effect of a base. Their chemical structures were confirmed previously via our work.⁴⁹ In parallel, hexane-1,6-diyl bis(2-chloroacetate) (3) was formed as a colorless viscous liquid with a yield of roughly 95% by reacting 1,6-hexanediol with chloroacetic acid and catalyzed by the acid catalyst PTSA in dry toluene as an essential solvent. Whereas the IR spectrum of compound 3 was utilized to elucidate the chemical structure through the ester group band's appearance at 1735 cm⁻¹, besides peaks for C–O and C–Cl at 1170 and 680 cm⁻¹, respectively. Secondly, a variety of two equivalent N-substituted sulphonamides (2a–e) were quaternized with hexane-1,6-diyl bis(2-chloroacetate) (3), individually in the presence of ethyl acetate as a solvent at 70 °C to produce the targeted ionic liquids incorporating sulphonamide groups (4a–e).

The FT-IR spectra of compounds 4a–e exhibited characteristic absorption peaks for NH of the amido group at about 3274–3369 cm⁻¹, and peaks at about 3091 cm⁻¹ for aromatic CH, peaks at about 2845–2975 cm⁻¹ for aliphatic CH. Furthermore, the IR spectrum showed a peak at about 1741–1745 cm⁻¹ for carbonyl of ester group and at about 1622–1632 cm⁻¹ for the C=N group, then peaks at about 1152–1154 cm⁻¹ for C–O–C bond (ether group). Furthermore, their ¹H NMR spectrum showed a signal for NH protons between 8.12 and 8.47 ppm, aromatic protons in the range 8.12–8.47 ppm, and protons adjacent to the quaternized nitrogen and oxygen of the ether group at 2.8–4.6 ppm. Also, the ¹³C NMR spectrum exhibited a peak between 164 and 166 ppm, which confirmed the presence of the carbonyl carbon atom of the ester group, aromatic carbon atoms at d = 120–145 ppm, and long-chain aliphatic carbon atoms (the deshielding aliphatic carbons) at d = 50–70 ppm and shielded aliphatic carbon atoms at d = 20–40 ppm. Finally, the ion exchange reaction was carried out by treating selected two synthesized compounds 4c and 4e with sodium tetrafluoroborate in a definite amount of acetone as solvent, for 10 h at 40 °C to obtain the targeted ionic liquid compounds bearing tetrafluoroborate anion (5c and 5e). The structures of synthesized compounds were elucidated via ¹⁵F NMR spectrum by the appearance of bands at 61.21 and 74.5 ppm, which related to the presence of fluorine atoms in the synthesized compounds.

As a model, the infrared spectra of 4a displayed, in addition to the bands already indicated, an extra band at 2233 cm⁻¹ that was attributed to the C–N group and an N–H band at 3374 cm⁻¹. Its ¹³C NMR spectra elucidated the presence of a signal at δ = 127 ppm for cyano-carbon, and aromatic carbon atoms at δ = 115–144 ppm (Fig. S2). Interestingly, the IR exhibited a special peak at 2231 for the cyano group (CN) that appeared only in compound 4a (Fig. S2–S8).

3.2. Collecting and dispersing of petroleum studies

Water surface pollution is mostly caused by oil leaks from storage tanks, pipelines, and transportation systems.⁵⁰ Thick oil stains are removed using technical techniques, but fine oil films are left on the water surface and can't be successfully removed using these techniques. Because they prevent sunlight from penetrating and interfere with oxygen exchange, these thin layers are a major hazard to marine life.⁵¹ Therefore, it is thought that the most effective way to remove these remaining thin oil films is to use agents that disperse and/or collect oil films.

Results showing the dispersion and collection capabilities of 4a–e, 5c, and 5e in 2.5% weight aqueous solution and solid states are summarized in Table 1 and Fig. 2. The effectiveness of 4a–e, 5c, and 5e as cleaning agents that disperse and/or collect oil films was affected by the aryl/heteroaryl sulfonamide moiety with a rigid spacer enhancing performance. Notably, in all used waters, compounds 4a, 4b, 4e, and 5e had a moderate effect on the dispersing or collecting of thin films from water surfaces in the diluted and undiluted forms, whereas K_D ranges from 56.44 to 66.11% and K ranges from 3.45 to 11.38. Unlikely, the undiluted form of 4c exhibited the greatest petro-dispersing action, whereas K_D = 82.42 in seawater and K_D = 83.32 in freshwater and a solid form. In contrast, the solid and solution forms of 4c demonstrated significant collecting stability for thin petroleum, whereas K ranged from 14.57 to 16.45 in the distilled water and maintained petro-collecting stability for four days. Interestingly, compound 4d showed the strongest effect as petro-dispersing and/or collecting action on the water surface. Whereas both forms of 4d demonstrated the accumulation of fine oil film in distilled water, as their K value equals 17.78 and 18.44, respectively, for 96 hours, with a high stability effect. Moreover, in diluted form, 4d also caused a highly dispersing effect of fine films after 96 hours, whereas the K_D values are 96.16 and 98.15% in sea and fresh waters, respectively. The solid form of 4d showed a good dispersing character of fine oil from the water surface, especially in the fresh and sea waters, whereas the K_D values were equal to 95.22 and 96.16%, respectively.

Table 1 Petro-collecting/dispersing properties of the synthesized ionic liquids compounds (4a–e and 5c, 5e)

Compd no.	Undiluted product						2.5% wt water solution
	Distilled water		Fresh water		Sea water		Distilled water		Fresh water		Sea water
	τ (h)	K(kD)	τ (h)	K(kD)	τ (h)	K(kD)	τ (h)	K(kD)	τ (h)	K(kD)	τ (h)	K(kD)
a NE = no effect.
4a	0–2	NE^a	0–2	5.33 ± 0.7	0–2	NE^a	0–2	NE^a	0–2	5.33 ± 0.9	0–2	NE^a
	30–96	5.28 ± 1.4	30–96	11.38 ± 1.5	30–96	4.66 ± 1.3	30–96	6.86 ± 1.6	30–96	10.86 ± 1.6	30–96	8.44 ± 1.6
4b	0–2	4.66 ± 0.8	0–2	3.45 ± 0.7	0–2	4.43 ± 0.8	0–2	4.34 ± 0.7	0–2	5.28 ± 0.7	0–2	5.67 ± 0.9
	30–96	9.87 ± 1.6	30–96	10.34 ± 1.3	30–96	7.98 ± 1.2	30–96	9.55 ± 1.5	30–96	10.55 ± 1.5	30–96	7.77 ± 1.5
4c	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a
	30–96	16.45 ± 1.2	30–96	83.32 ± 1.3%	30–96	80.11 ± 2.1%	30–96	14.57 ± 1.5	30–96	81.21 ± 2.3%	30–96	82.42 ± 1.8%
4d	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a
	30–96	17.78 ± 1.2	30–96	95.22 ± 1.6%	30–96	96.16 ± 2.6%	30–96	18.44 ± 1.5	30–96	96.16 ± 2.6%	30–96	98.15 ± 1.5%
4e	0–2	NE^a	0–2	5.31 ± 0.7	0–2	NE^a	0–2	NE^a	0–2	4.13 ± 0.9	0–2	NE^a
	30–96	6.11 ± 1.4	30–96	9.55 ± 1.8	30–96	66.11 ± 1.6%	30–96	6.13 ± 1.8	30–96	10.86 ± 1.7	30–96	56.44 ± 1.6%
5c	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a	0–2	NE^a
	30–96	15.66 ± 1.8	30–96	81.44 ± 1.9%	30–96	83.22 ± 2.2%	30–96	11.66 ± 1.7	30–96	83.33 ± 1.8%	30–96	78.33 ± 1.6%
5e	0–2	NE^a	0–2	5.31 ± 0.7	0–2	NE^a	0–2	NE^a	0–2	4.13 ± 0.9	0–2	NE^a
	30–96	6.77 ± 1.7	30–96	10.66 ± 1.9	30–96	63.11 ± 1.2%	30–96	7.01 ± 1.6	30–96	9.22 ± 1.3	30–96	59.44 ± 1.1%

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Fig. 2 Effect of the synthesized ionic liquid (4d) on petroleum. (A) Untreated thin film, (B) petro-collecting, and (C) petro-dispersing.

After modification of the structure of synthesized compounds 4c and 4e, a suitable model was formed to form a new structure as 5c and 5e. Table 1 shows that the petroleum properties of synthesized compounds 5c and 5e exhibited slightly different effects compared to those of compounds 4c and 4e; this difference is attributed to the structural change, specifically the alteration of the negative ion from Cl⁻ to BF₄⁻. The hydrophobic part plays an important role in determining the petroleum effects and the strength of the effect, and this feature appears clearly in compound 4d, which gave the greatest effects due to the presence of six isopropyl groups (high hydrophobic part).

Building on our previous work, the synthesized compound 4d proved to be a more effective petro-dispersing agent for removing petroleum films than the earlier reported compounds 3a–g.⁵² In addition, the present study revealed that 4d surpassed the dispersing capabilities of PS2 and PS3.⁵³ Remarkably, compound 4d also showed greater efficiency than the comparable AISM and AISE compounds in cleaning petroleum-contaminated water surfaces.⁵⁴ (All abbreviations are reported in the SI, Table S1).

3.3. Larvicidal activity against Culex pipiens larvae

The synthesized compounds had moderate toxicity against the third instar of C. pipiens larvae. The mortality percentages of C. pipiens larvae varied with the different concentrations of the investigated compounds. The high concentration of 800 ppm showed mortality percentages of 73.33, 90, 81.66, 98.33, 78.33, 70, and 86.66% for 4a, 4b, 4c, 4d, 4e, 5c, and 5e, respectively, as shown in Fig. 3. On the other hand, the lowest concentration, 100 ppm, exhibited 18.33, 35, 26.66, 38.33, 20, 13.33, and 33.33% for 4a, 4b, 4c, 4d, 4e, 5c, and 5e, respectively, as represented in Fig. 3. Temephos achieved high mortality of 93.33% at 400 ppm (Fig. S9).

Fig. 3 Mortality percentages of early third larval instar of Culex pipiens after exposure to ionic liquids incorporating sulfonamide moiety derivatives (4a–e, 5c, 5e), 48 h post-treatment.

The probit regression analysis between concentration and mortality was used to calculate the LC₅₀ and LC₉₀ values for all tested compounds (Table 2). According to the LC₅₀ values, 4d was the most effective compound with LC₅₀ values of 161.03 ppm, followed by 4b and 5e with 207.82 and 229.72 ppm, respectively (Table 2). The least active compounds, 4a and 5c, had LC₅₀ values of 424.47 and 495.78 ppm, respectively. The relative potency was estimated for tested compounds relative to the least active; 5c, 4d, 4b, and 5e were 3.07, 2.38, and 2.15 times more potent than 5c. The tested population showed a homogeneous response to all tested compounds except 4d, with an χ² value of 8.17.

Table 2 Larvicidal toxicity parameters of ionic liquids incorporating sulfonamide moiety derivatives (4a–e, 5c, 5e) against early third instar larvae of Culex pipiens at 48 h post-treatment

Compd (ppm)	LC50 (F.l. at 95%)^a	LC90 (F.l. at 95%)^a	Slope ± SE^b	χ^2^c	P	Relative potency
a F.l.: fiducial limits.b Slope ± SE: slope of concentration-mortality regression line ± standard error.c χ^2: chi-square at significance value (<0.05); relative potency calculated relative to compound 5c.
4a	424.47 (360.06–510.43)	2615.07 (1748.71–4893.04)	1.62 ± 0.19	3.81	0.28	1.16
4b	207.82 (169.01–245.86)	1187.41 (895.46–1799.11)	1.69 ± 0.18	6.80	0.07	2.38
4c	282.70 (236.58–332.57)	1700.92 (1219.24–2812.74)	1.64 ± 0.18	3.47	0.32	1.75
4d	161.03 (90.53–213.68)	593.33 (455.04–1155.72)	2.26 ± 0.20	8.17	0.04	3.07
4e	341.87 (292.37–399.58)	1832.59 (1324.51–2969.70)	1.75 ± 0.19	2.15	0.54	1.45
5c	495.78 (424.23–596.52)	2618.16 (1792.26–4671.05)	1.77 ± 0.20	3.20	0.36	1.00
5e	229.72 (188.00–271.64)	1390.10 (1021.14–2207.25)	1.63 ± 0.18	6.24	0.10	2.15
Temephos	119.44 (63.88–175.16)	529.98 (439.68–1911.71)	1.98 ± 0.19	9.67	0.02	4.15

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The absence of hydrophobic alkyl substituents in the ionic liquid (ILs) molecules increased their solubility in water. The synthesized ionic liquids are soluble in water, which facilitates application as larvicides. A cation salt was proven to be an effective antifeedant against stored product insects. Didecyldimethylammonium cations exhibited excellent activity and are commercially available in the chloride form; therefore, ILs become a promising alternative to the currently used insect antifeedants. To design new active ILs, the biological roles of cations, arylsulphonamide derivatives, and halogens were studied. The synthesized salts by Pernak⁵⁵ showed insect antifeedant activities towards larvae and/or adults of Tribolium confusum, Sitophilus granaries, and Trogoderma granarium by estimating the amount of consumed food. ILs showed antifeedant activity against the rice weevil, the granary weevil, khapra beetle, and the confused flour beetle; especially those with long alkyls (hexadecyl and tetradecyl) had the highest efficacy. The results indicated that the alkyl substituent length was an essential parameter that substantially improved the antifeedant activity of ILs.⁵⁶

From the previous studies, it was noted that most of the ILs were used as deterrents or antifeedant agents, while few studies showed insecticidal properties, leading to mortality. The contact activity is influenced by the length of the alkyl chains in the cation and the functional groups. The ionic liquids exhibited deterrent activity against storage insects, and the alkyl length of the linker and the ester bond in the cation are the main determinants of their biological activity.⁵⁷ Also, the ionic liquid 3-(2-((3,7-dimethyloct-6-en-1-yl)oxy)-2-oxoethyl)-1-methyl-1H-imidazol-3-ium chloride showed remarkable mortalities of 68–88% and 63–76% towards Callosobruchus analis F. and Sitophilus oryzae L. at 5 and 10 µL, respectively, after 24 h of treatment. In addition, it exerted oviposition deterrence on females of C. analis, therefore, there was a reduction in egg hatchability and progeny production even at low concentrations.⁵⁸ A monoterpene-based ionic liquid exhibited adulticidal, larvicidal, repellent, and antifeedant activity against Tribolium castaneum Herbst and Stegobium paniceum L.⁵⁹ Adults of C. pipiens were treated with aminopyridinium-based IL derivatives by two methods: spraying and orally. Accumulated mortality rates were higher in sprayed mosquitoes than in those orally treated.⁶⁰

3.4. Structure–activity relationship study

The synthesized compounds have a common scaffold, a bis-ether linker [(hexane-1,6-diylbis(oxy))bis(2-oxoethane-2,1-diyl)], two quaternary ammonium groups with N,N-dimethylpropan-1-aminium and counter ions (Cl⁻ or BF₄⁻). This scaffold has amphiphilic behavior, causing disruption of the cell membrane.⁶¹ Also, it exerts electrostatic interaction with negatively charged components in insect cuticles or membranes.⁶² Compound 4d was the most active compound, since it had a pair of triisopropylphenylsulfonamide. The presence of these polycyclic aromatics enhanced the interaction with the hydrophobic cuticle of larvae, boosting penetration through the cuticle. Additionally, this aromatic group can form π–π stacking interactions with chitin or active protein targets in the insect body, thereby enhancing the larvicidal activity. 4b contained thiophene-2-sulfonamide, which enhances the activity. Thiophene-containing derivatives showed beneficial activity against C. pipiens larvae.⁶³ Additionally, the presence of electron-withdrawing Cl increases lipophilicity that may lead to oxidative disruption in insect tissues.

In 5c and 5e, the counterion Cl⁻ was replaced by BF₄⁻, which modified the ionic strength and solubility and could improve environmental persistence. Moreover, BF₄⁻ is a less reactive counterion that may reduce cytotoxicity and enhance stability in aqueous environments. 5e, 4-methylphenylsulfonamide with BF₄⁻, showed good activity; hence, the insertion of a methyl group at the meta position leads to resonance in the phenyl group and boosts contact toxicity. On the other hand, 5c showed the least toxicity as a result of the linkage of a large bulking naphthalene moiety to sulfonamide.

The sulfonamide quaternary ammonium compounds look promising as larvicides and as petro-collecting/dispersing agents. The surfactant action and the significant larvicidal activity of quaternary ammonium groups suggest that they can be developed into mosquito control agents, helping reduce disease spread and collect or disperse oil spills to aid environmental cleanup. These multifunctional compounds offer great potential for eco-friendly larvicides and environmental clean-up agents. According to the SAR study, the long hydrophobic chain halogenated aromatic groups and presence of methoxy groups greatly enhanced the activity. Further work can optimize their structure to balance bioactivity and environmental safety. Also, more studies on formulations were needed for efficient delivery in water environments will be key for practical use in pest control and oil spill remediation.

4. Conclusion

In this work, a series of novel ionic liquid-based sulphonamides (4a–d, 5c, 5e) was effectively synthesized tethering a bis-ether linker, two quaternary ammonium groups, and numerous aryl/heteroaryl sulphonamide moieties. These ionic liquids were tested to disperse or collect thin petroleum films from water surface, as well as kill larvae.

The results approved their effectiveness as pesticides in controlling mosquitoes and as collecting/dispersing agents for removing oil films. Compounds 4c, 4d, and 4e exhibited better activity in dispersing and collecting small layers of petroleum from water. The best result was achieved by compound 4d, with good dispersion (K_D up to 98.15%) and collection stability (K up to 18.44) in both solid and liquid forms. The presence of large hydrophobic groups, especially isopropyl groups in 4d, made it much better at interacting with oil. In compounds 5c and 5e, displacement of the chloride counterion to the borofluoride ion had a slight effect on their response to petroleum layer. In addition, compound 4d with its triisopropylphenylsulfonamide moiety possessed the best activity at killing larvae (LC₅₀ = 161.03 ppm). This moiety facilitates the penetration of the compound molecules to the larval cuticle and breaking down the membrane of cells. Furthermore, the presence of BF₄⁻ anion in compounds 5c and 5e instead of Cl⁻, made them less reactive and more stable, and hence safer to the environment.

Generally, these conjugates represent compounds with dual functionality that can be used to clean up the water surfaces from oil spills and control mosquitoes that carry disease.

Conflicts of interest

All authors declare that they have no conflict of interest.

Data availability

All data are available upon request from the authors.

Supplementary information is available. See DOI: https://doi.org/10.1039/d5ra07077e.

Acknowledgements

This research has been funded by Scientific Research Deanship at University of Ha'il – Saudi Arabia through project number “RG-23 079”.

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