Elena V.
Khramenkova
a,
Mikhail V.
Polynski
*a,
Alexander V.
Vinogradov
a and
Evgeny A.
Pidko
*ab
aTheoMAT group, International Laboratory “Solution Chemistry of Advanced Materials and Technologies”, ITMO University, Lomonosova str. 9, St. Petersburg 191002, Russia. E-mail: polynskimikhail@gmail.com
bInorganic Systems Engineering group, Department of Chemical Engineering, Faculty of Applied Sciences, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands. E-mail: E.A.Pidko@tudelft.nl
First published on 18th June 2018
Stability is the key property of functional materials. In this work we investigate computationally the degradative potential of a model Mn-BTC (BTC = benzene-1,3,5-tricarboxylate) metal–organic framework (MOF) building block in aqueous solutions under oxidative conditions. Model density functional theory calculations have shown that the direct hydrolysis of the Mn-containing moieties is more difficult than their decomposition via oxidation-induced paths. While the interaction with H2O2 species is of non-covalent nature and requires O–O-bond breaking to initiate Mn-center oxidation, open-shell O2 species readily oxidize radical Mn-centers and form bonds of σ-, π-, or δ-symmetry with the metal. The oxidative transformations of di-Mn paddle-wheel carboxylate structure-forming units are accompanied with substantial distortions of the coordination polyhedra that, together with the increased Lewis acidity of the oxidized metal centers, facilitates the hydrolysis leading to the degradation of the structure at a larger scale. Whereas such a mechanism is expected to hamper the catalytic applications of such Mn-MOFs, the associated structural response to oxidizing and radical species can create a basis for the construction of Mn-MOF-based drug delivery systems with increased bio-compatibility.
Fundamentally different requirements to material properties arise for biomedical applications. There is a growing interest in the utilization of inorganic chemistry polymers, including MOFs, in the development of multifunctional biomedical materials.13,14 Here, the intrinsic instability of the hybrid organic–inorganic framework can be regarded as an advantageous feature enabling programmed degradation of the material.15,16 The possibility of the programmed decomposition of an inorganic matrix into molecular building blocks17,18 facilitates its removal from the organism as well as driving the controlled and targeted release of bio-active materials.19,20 Therefore, MOFs are considered promising for the construction of responsive matrices and carriers for smart drug delivery systems.21,22 Their predictable and tunable chemistry on the molecular level creates a possibility to design chemical response mechanisms to varying environmental conditions, i.e.,23 one can design these materials to respond to specific changes in the microenvironment of pathological tissues. Acidosis, elevated tissue temperature, and formation of reactive oxygen species (ROS) are the specific signals that can direct the targeted delivery of an active pharmaceutical ingredient (API) to a pathologic area.24–26 MOFs readily satisfy the essential requirements for smart drug delivery platforms, which are controllable degradation, biocompatibility and simplicity of chemical functionalization. They may be synthesized from biocompatible components as non-toxic metals and organic ligands. The medical use of widely explored Fe- and Cr-based MOFs is limited due to the toxicity issues, although such MOFs are able to upload high amounts of API.27 In this context, Mn-based inorganic systems are particularly appealing owing to their low toxicity combined with Mn-rich coordination chemistry. While being toxic only at a high dosage,28 Mn regulates biological processes and is a component of many enzymes.29–31
Mn-Based MOFs are also considered as catalysts for a number of important chemical processes. In particular, such Mn-MOFs as [Mn3(atpa)3(dmf)2] and [Mn2(tpa)2(dmf)2] were investigated as effective Lewis acid catalysts for the cyanosilylation of acetaldehyde (atpa = 2-aminoterephthalate, tpa = terephthalate, dmf = dimethylformamide).32 The oxidative degradation of phenol catalyzed by bimetallic Fe/Mn-MOF-71 was studied by Sun et al.33 According to Pereira et al.,34 Mn-based PIZA, RPM and ZJU MOF families are catalytically active for alkane oxidation.
The behavior of Mn-based MOFs in oxidative environments has been a subject of several experimental studies. Depending on the nature of the ligands and the MOF structure, the intrinsic structural stability under harsh reaction conditions may vary substantially.35–37 Zuluaga et al. have reported Mn-MOF-74's (Mn2(DOBDC), DOBDC = 2,5-dioxido-1,4-benzenedicarboxylic acid) susceptibility to hydrolysis that led to the degradation of the structure and limited the sorption capacity of the material.38 On the other hand, the report by Wu et al. demonstrated the perfect structural stability of a defected Mn-MOF-74 when exposed to water for up to 7 days.39 The same framework material has been further employed for the catalytic oxidation of alkyl aromatics in an O2 flow.40 Hansen et al. reported an Mn-based catalyst featuring 2,2′:6′,2′′-terpyridine structure-forming ligands as an active oxidation catalyst capable of retaining structural integrity in the catalytic oxidative environment.41 MOF structures featuring Mn(3+)-porphyrin catalytic motifs have been reported as active and highly durable olefin oxidation catalysts.42 An alternative IRMOF-3(Mn) catalyst made of Mn-carboxylate units was also found to be stable under the conditions of the gas-phase selective oxidation of alkenes.43 Importantly, a wide range of catalytic studies have explored the reactivity of MOFs in non-aqueous media.42–46 In biological systems, the aqueous environment may potentially make either direct or oxidation-induced hydrolysis possible as the routes for controlled decomposition of Mn-MOF. The stability of materials in oxidative environments has been the subject of computational studies as well.47–49
The interaction of MOF-based materials with the oxidizing species is thus of key importance for pharmaceutical chemistry and catalysis. The knowledge of the corresponding mechanisms on the molecular level may help to determine whether, on the one hand, a MOF material under consideration will irreversibly interact and (controllably) degrade under oxidative conditions. The understanding of controllable degradation mechanisms will allow for the construction of new targeted drug delivery systems. On the other hand, the material may be stable towards oxidizing species, reacting reversibly and activating them. Therefore, the understanding of the MOF-oxidizing species’ interaction mechanism may direct new oxidation catalyst development as well.
The focus of the present computational study is the reactivity of the Mn-BTC framework (BTC = benzene-1,3,5-tricarboxylate, Fig. 1a) towards oxidizing species (O2 and H2O2) in aqueous media. We show that the oxidative transformations of the Mn centers in MOFs can potentially be employed as the driver for controlled degradation of Mn-MOF-based nanocontainers in response to increased levels of oxidants produced in pathologic tissues. We computationally evaluated the energetics of the reaction mechanisms corresponding to the MOF–O2- and MOF–H2O2-interactions in aqueous media. The results provide guidance towards the further design of responsive structures for a wider range of applications, including smart drug delivery systems. Besides, the insights into the processes determining the structural (in)stability of Mn-BTC frameworks under oxidative conditions are crucial for their utilization in oxidation catalysis.
The interaction with O2 and H2O2 molecules and local structural deformations that could initiate the material degradation processes were investigated in the cluster-continuum approach. The cluster model representing the Mn-carboxylate paddle-wheel configuration was cut from a periodic structure of Mn-BTC MOF (Fig. 1a). The resulting cluster fragment of [Mn2(PhCOO)4] was then coordinatively saturated by the inclusion of two water molecules. The geometries of all cluster models were optimized without any geometry constraints to satisfactorily represent the substantial geometrical flexibility and relaxation potential of the coordination polymers.56,57 The effect of possible steric inflexibility was tested by the set of constrained optimizations, in which the positions of the para-H atoms of the PhCOO− units were fixed. These constrained test optimizations were carried out on the configurations corresponding to the most stable (in terms of exothermicity of formation) and distorted complexes obtained through the unconstrained optimizations. The computed energetics and optimized structures are summarized in the Supporting Information for the article (Fig. S1, S2 and Table S1, ESI†). These tests evidence the key role of the structural flexibility for the preservation of the optimal coordination environment of the Mn centers. The excessive geometrical strain imposed by the fixed positions of the para-H-atoms in PhCOO− ligands gave rise to the decoordinaton of Mn-centers in some cases.
All L[Mn2(PhCOO)4]L model complexes (where L is H2O, H2O2, or O2) were considered in various spin states (namely, S = 6/2, 8/2, 10/2) while in the case of H2O[Mn2(PhCOO)4]O2 and O2[Mn2(PhCOO)4]O2 complexes, S = 12/2 and 14/2 spin states were also considered. Initial test calculations indicated that the other electronic configurations (including the lower-spin and broken symmetry configurations, see below) are characterized by excessively high energies and are therefore not relevant to the processes considered here.
The concurrent adsorption energies (Eads) of the oxidizing species were calculated according to the formula:
Eads = En−OX-Mn-BTC + nEH2O − EAQUA − nEOX |
The molecular orbital isosurfaces used for the analysis of bonding in the adsorption complexes were constructed with the ChemCraft program.58
In aqueous solution, the open axial coordination sites are likely to be occupied by H2O molecules. Among the H2O[Mn2(PhCOO)4]H2O complexes, the one with S = 10/2 spin state, the 110/2 complex (Fig. 1c), was energetically preferred, and the low-spin S = 8/2 (18/2) and 6/2 (16/2) states had higher energies (43 and 54 kJ mol−1, respectively). Thereby, 110/2 formation from the [Mn2(PhCOO)4] complex in the 10/2 spin state is exothermic by −84 kJ mol−1. The formation of the antiferromagnetic state was unlikely in the case of the H2O[Mn2(PhCOO)4]H2O complex as well since the broken-symmetry computation at the PBE-D3/6-311++G(d,p)//PBE-D3/6-31G(d,p) level (PCM solvation included) showed that the singlet state had 332 kJ mol−1 higher energy compared to the 10/2 state. The Mulliken spin densities in the Mn-centers in the singlet state were 4.5 and −4.5 a.u.
Water-bound cluster 110/2 (Scheme 1) was selected as the reference point and starting configuration for further modeling the interaction of Mn-BTC with the oxidizing species. It is worth noting that the overlap between H2O and [Mn2(PhCOO)4] fragments in 110/2 is negligible (Fig. 1c), although the binding is highly exothermic (ΔEads = −84 kJ mol−1). The coordination of H2O molecules results in the formation of the four hydrogen bonds between OH groups and the oxygen atoms of the carboxylate ligands. Thus, the highly exothermic effect of H2O binding may be caused by the formation of strong hydrogen bonds and the reduction of electrostatic repulsion between Mn2+ cations owing to the countering electrostatic field of H2O dipoles.
Scheme 1 summarizes the chemical transformations that are considered here as potential pathways for the oxidative degradation of Mn-BTC in the presence of O2 or H2O2 species. The model oxidants are relevant to both biological and catalytic potential applications of Mn- and carboxylate-based metal–organic frameworks. Note that, depending on the spin-state, coordination complexes of different structures are formed; Scheme 1 explicitly indicates them with the appropriate labels. Fig. 2 graphically summarizes the relative energies of the formation of the oxidated complexes. These oxidative transformations are discussed in more detail in the subsequent sections.
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Fig. 2 The concurrent adsorption energies (Eads, see Section 2) of the O2 and H2O2 oxidizing species to H2O[Mn2(PhCOO)4]H2O complex. |
The binding in both coordination modes results from the overlap between singly-occupied O2 π* orbitals and 3d orbitals of Mn that are singly occupied as well, and the formation of the particular configuration leads to different spin states. Whereas the formation of the η1 complex preserves the spin state (with the corresponding structure being 2b10/2, see Scheme 1), the formation of δ complexes with η2-bound O2 ligand leads to the electron pairing and the formation of 2a6/2 and 2a8/2 complexes in 6/2 and 8/2 spin states, respectively. The formation of the latter is strongly exothermic. The reaction energies computed for water exchange 1 → 2 are −24 and −62 kJ mol−1 for the formation of 2a6/2 and 2a8/2, respectively (Fig. 2). The formation of the σ-type bound 2b10/2 complex in the 1 → 2 process has a weak exothermic effect of −1 kJ mol−1. The chemical irrelevance of the high-spin 12/2 state was ensured with the computed binding energy of 42 kJ mol−1 (see Fig. S3a, ESI†).
The complexation with O2 distorts the initial square pyramidal geometry of the Mn centers in 110/2 to form a distorted octahedron in 2a6/2 and trigonal bipyramid in 2a8/2 of O2-coordinated Mn sites. The water-coordinated site in 2a6/2 has octahedral geometry while the H2O-bonded Mn2+ center in 2a8/2 has severely distorted trigonal-bipyramidal geometry with the cleaved Mn–Mn bond. Mn centers in 2b10/2 form highly distorted octahedrons (Fig. 3c).
The end-on-bound O2 molecule in 2b10/2 may formally be considered as a superoxide (O2−) ligand, which implies the formal oxidation of Mn(2+) to Mn(3+). The formal oxidation state of oxygen-bound Mn cations in 2a6/2 and 2a8/2 complexes should then be considered as Mn(4+) with the side-on bound peroxide (O22−) ligands.
The changes in the Mn oxidation states are in line with the Mulliken spin density changes in reaction 1 → 2 (Scheme 1). The O2 binding in the case of 2b10/2 leads to the decrease of the spin density on the interacting Mn (from 4.80 to 3.56) and the asymmetric decrease from (1, 1) to (0.70, 0.82) of the spin densities on O atoms in the O2 molecule (see Table S2, ESI†). Based on the analysis of the spatial distribution of Kohn–Sham orbitals, σ-symmetry bonding is evident when a single O atom is bound to Mn. This implies the formation of an Mn center in the formal (3+) oxidation state.
The δ binding of the O2 species proceeded via the electron density donation by Mn d electrons to the π* orbitals of O2 molecules resulting in the weakening of the O–O bond. This is reflected in the significant increase of the O–O bond length in 2a8/2 and 2a6/2 structures (r(O–O) = 1.411 Å and 1.373 Å, respectively) when compared to that in the dioxygen molecule (r(O–O) = 1.228 Å). The analysis of the electron density distribution in 2a6/2 shows the decrease of spin density on oxygen atoms in the O2 molecule (from (1, 1) to (0.15, 0.15) a.u.) and the reduction of spin density values on the corresponding Mn site (from 3.16 to 2.33). A similar trend was found in 2a8/2 where spin densities on the Mn site and the coordinated O2 decreased from 3.28 to 2.94 and from (1, 1) to (0.11, 0.10), respectively (see Table S2, ESI†). These changes indicate the formation of the Mn(4+) formal oxidation state in both cases.
The reaction of 2a and 2b complexes with a second O2 molecule leads to the formation of two isomers (end-on-end-on and side-on-end-on) of the three possible ones (2 → 5 step on the Scheme 1). The formation of the side-on-side-on O2[Mn2(PhCOO)4]O2 isomer was not observed owing to the significant steric strain of the [Mn2(PhCOO)4] core imposed by the side-on binding of O2 species (see the discussion above and Fig. 3a–c).
The σ-type bonding of two oxygen molecules leads to an end-on-end-on configuration with the octahedral coordination of both Mn cations. The formation of the corresponding 5a6/2 complex proceeded with a low exothermic effect of −5 kJ mol−1 (Fig. 4a). The side-on-end-on configuration corresponds to the simultaneous binding of O2 species in δ- and σ-modes and the formation of 5b8/2 and 5b10/2 complexes is exothermic by −26 and −15 kJ mol−1, respectively (Fig. 4b and c). Here, both Mn centers adopt square pyramidal geometry.
The Mn centers having an η2-bound O2 ligand in 5b8/2 and 5b10/2 isomers were in Mn(4+) oxidation state as follows from the significant alternation of the spin densities upon their formation that is the spin density on the O atoms of the ligand changes from (1, 1) to (−0.27, −0.27) and (0.15, 0.15), respectively. At the same time, the spin density at the η1-bound O2 ligand in 5b8/2 and 5b10/2 changed from (1, 1) to (0.38, 0.46) and (0.78, 0.93), respectively, suggesting the oxidation of the metal center to the Mn(3+) state (see Table S2, ESI†).
The 514/2 spin isomer corresponds to weak non-covalent bonding. Particularly, the lack of close Mn–O contacts is evident in the optimized structures (see Fig. S3b, ESI†) and the corresponding reaction energy is equal to 84 kJ mol−1.
The Mn(3+) state is known to easily disproportionate leading to Mn(2+) and Mn(4+) formation in aqueous solutions.60 Accordingly, our calculations show that the formation of η1-bound O2 complexes, which are the superoxide-bound (O2−) Mn(3+) cations in L[Mn2(PhCOO)4]L, is the least exothermic reaction (5a6/2 and 2b10/2 formation) among the alternative pathways. Therefore, we conclude that the oxidation of Mn-BTC MOF with O2 forming Mn(3+) centers is less likely than the two-electron oxidation paths resulting in the oxidized structures with more stable Mn(4+) centers.
Compared to the exothermic step 1 → 2, in which the first O2 molecule binds, the binding of the second O2 molecule is strongly endothermic. The formation of 5a6/2 and 5b8/2 increases the energies of the systems by 19 and 36 kJ mol−1 compared to 2a6/2 and 2a8/2, respectively. Only formation of the σ-type bound complex 2b10/2 is exothermic by −14 kJ mol−1. The unfavorable binding of the second O2 molecule in the cases of δ complexes is supposedly a result of the distorted and, consequently, more sterically strained structure of the oxidized species. The results above on the facile oxidation and substantial structural distortions of the coordination sphere of Mn centers upon O2 coordination imply that the degradation of Mn-BTC MOFs can already be induced at low O2 concentrations, thus creating an opportunity to develop O2-selective response matrices as a basis for new smart drug delivery platforms.
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Fig. 5 The geometries (front and side views) of the H2O[Mn2(PhCOO)4]H2O2 complex in S = 6/2 (a) and 10/2 (b) spin states optimized at the PBE-D3/6-31G(d,p) level of theory. |
The binding of the second H2O2 molecule via the 3 → 6 process proceeded with the retention of the coordination polyhedra and led to the formation of 66/2 and 610/2 (Fig. 6). These reactions had thermal effects of 27 and −23 kJ mol−1, respectively.
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Fig. 6 The geometries (front and side views) of the H2O2[Mn2(PhCOO)4]H2O2 complex in S = 6/2 (a) and 10/2 (b) spin states optimized at the PBE-D3/6-31G(d,p) level of theory. |
The exchange of two water ligands with H2O2 leads to the coordination bond, which is accompanied by a negligible decrease of the Mulliken spin density on the Mn centers in both 16/2 → 66/2 and 110/2 → 610/2 transformations (from 3.16 to 3.14 and from 4.80 to 4.77, respectively; see Table S2, ESI†). These changes clearly show that the binding of H2O2 is not accompanied by the oxidation of the Mn centers. The final complexes in the 1 → 3 and 3 → 6 steps are stabilized via the formation of the five-membered cycles with the hydrogen bonds between oxygen atoms of the carboxylate ligands and the OH groups of the bound H2O2 species (r(OH⋯O) = 1.7–2.0 Å). In the case of 66/2 and 610/2, two H2O2 molecules bound to both Mn sites form two five-member cyclic structures contributing to their increased stability, resulting in the thermodynamic favorability of the ligand exchange.
The oxidation-assisted hydrolysis thus starts with the substitution of the water molecules in the solvated 110/2 structure discussed in detail previously and the formed 66/2 and 610/2 intermediates undergo further oxidation (Fig. 6). The transition state on the potential energy surface with 10/2 spin state is denoted as TS10/2 and corresponds to a barrier of 21 kJ mol−1. The computed imaginary frequency of the TS10/2 structure has the value of i365 cm−1, corresponding to the O–O-bond stretching in the H2O2 moiety and the neighbouring Mn site has the trigonal-bipyramidal coordination polyhedron. After passing TS10/2, the relative order of the potential energy surfaces with S = 10/2 and 6/2 changes and the system may undergo a spin crossing.
For the high-spin complex 710/2, the O–O bond cleavage in the peroxide moiety leads to Mn(4+) center formation, which has octahedral geometry and bears two terminal OH ligands. The oxidation is accompanied with the reduction of the Mulliken spin density value in the Mn center (4.78 to 3.90 a.u.; Table S3, ESI†). The reaction energy for the latter process is −87 kJ mol−1. The subsequent hydrolysis leads to H2O binding to the Mn(4+) site through the formation of the hydrogen bonds between H atoms of H2O molecule and O sites of the hydroxyl and benzoate ligands. The corresponding intermediate is denoted as 810/2 (Fig. 8). The non-valent H2O molecule coordination does not alter the octahedral geometry of the Mn(4+) centers.
The Mn-BTC degradation via the 6/2 pathway was thermodynamically preferred according to the modeling results. The 76/2 intermediate had −146 kJ mol−1 lower energy relative to the 110/2 level and −59 kJ mol−1 lower relative to the 710/2 counterpart. We expect the 66/2 to 76/2 transition to be barrierless. Particularly, the “barrier” of −1 kJ mol−1, which was computed at the PBE-D3/6-311++G(d,p)//PBE-D3/6-31G(d,p) level with the PCM solvation model, could be an inaccuracy caused by the solvation model that was applied in post-optimization single-point energy refinement. The imaginary mode in the TS6/2 structure corresponded to O–O bond stretching and had the frequency of i261 cm−1 as computed at the PBE-D3/6-31G(d,p) level of theory. The oxidized Mn(4+) center in the 76/2 intermediate had a trigonal-bipyramidal structure bearing the oxo-ligand. The spin density value decreased from 3.14 to 2.33 a.u. in 66/2 → 76/2 (Table S3, ESI†). Then oxidized 76/2 species underwent a strongly exothermic (ΔE = −165 kJ mol−1) hydrolysis step. The Mn center adopted the octahedral coordination in the 86/2 intermediate formed upon the hydrolysis.
The structural flexibility of the unconstrained cluster model provides sufficient space for the relaxation upon the interaction with the oxidative species needed to ensure the overall stability of the extended periodic structure composed of such units. Here we infer that the potential degradation paths are initiated when the ROS binding induces severe structural deformations that substantially alter the coordination polyhedra of the Mn sites. Although the introduction of the hard geometric constraints decreased the exothermicity of the formation of the adsorption complexes (Fig. S1 and Table S1, ESI†), the effects were minor and did not affect the main conclusions made on the basis of the fully relaxed models that have been discussed above. In some cases, we, however, observed the enhancement of the reactivity of the Mn sites owing to the excessive strain provided by the constrained benzoate ligands, which resulted in some cases in decoordination events and structural alteration of the otherwise stable geometries (Fig. S2, ESI†). These effects appear to be highly model-dependent and are not expected to be representative to the sufficiently flexible MOF structures that are captured by the relaxed cluster models.
The calculations indicated the sufficient stability of the Mn-carboxylate structure-forming units towards direct hydrolysis while the interaction with the O2 and H2O2 species led to a facile oxidation of the Mn(2+) to the more thermodynamically stable Mn(4+) state. The oxidation was proceeded with a substantial deformation of the coordination sphere of the transition metal centers and, accordingly, facilitation of the subsequent hydrolysis of the coordination bonds.
DFT calculations showed a facile exchange of non-covalently bound H2O ligands at the Mn(2+) centers in the Mn-BTC with molecular O2 resulting in covalent σ, π, or δ bonding. The latter path was more favorable and it resulted in the oxidation of the Mn center to the formal (4+) state and the formation of a peroxide adduct. The formation of the Mn(3+) state was the result of the O2 ligand complexation in the σ bonding mode and was likely the intermediate state in the formation of the more stable Mn(4+) counterpart.
On the contrary, hydrogen peroxide molecules bind weakly to the Mn sites. The respective ligand exchange reaction with the starting aqua complex was an exothermic process for the high-lying spin state. The H2O2-induced degradation of Mn-BTC in aqueous media involved the cleavage of the O–O bond in the coordinated H2O2 molecules, resulting in the oxidation of the Mn(2+) center to the (4+) state, which strongly facilitated the subsequent hydrolysis. Importantly, we note the importance of spin transitions for all reaction paths considered in this study. This has to be properly accounted for in further studies on the stability of Mn-based MOF materials. Our current results clearly show the limited potential of Mn-carboxylate building blocks for oxidation catalysis or gas-sorption applications where the interactions with potential ROS species will inevitably result in the structural distortion of the framework and the long-term degradation of the functional materials. Nevertheless, the favorable reaction paths identified here may be utilized for engineering a new mechanism of the structural response of Mn-containing nanocontainers to pathology-induced alterations of biological environments.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cp00397a |
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