Dithiolene Moiety Research Articles

Integrating Multiple Redox‐Active Units into Conductive Covalent Organic Frameworks for High‐Performance Sodium‐Ion Batteries

AbstractThe rational design of porous covalent organic frameworks (COFs) with high conductivity and reversible redox activity is the key to improving their performance in sodium‐ion batteries (SIBs). Herein, we report a series of COFs (FPDC‐TPA‐COF, FPDC‐TPB‐COF, and FPDC‐TPT‐COF) based on an organosulfur linker, (trioxocyclohexane‐triylidene)tris(dithiole‐diylylidene))hexabenzaldehyde (FPDC). These COFs feature two‐dimensional crystalline structures, high porosity, good conductivity, and densely packed redox‐active sites, making them suitable for energy storage devices. Among them, FPDC‐TPT‐COF demonstrates a remarkably high specific capacity of 420 mAh g−1 (0.2 A g−1), excellent cycling stability (~87 % capacity retention after 3000 cycles, 1.0 A g−1) and high rate performance (339 mAh g−1 at 2.0 A g−1) as an anode for SIBs, surpassing most reported COF‐based electrodes. The superior performance is attributed to the dithiole moieties enhancing the conductivity and the presence of redox‐active carbonyl, imine, and triazine sites facilitating Na storage. Furthermore, the sodiation mechanism was elucidated through in situ experiments and density functional theory (DFT) calculations. This work highlights the advantages of integrating multiple functional groups into redox‐active COFs for the rational design of efficient and stable SIBs.

Integrating Multiple Redox-Active Units into Conductive Covalent Organic Frameworks for High-Performance Sodium-Ion Batteries.

The rational design of porous covalent organic frameworks (COFs) with high conductivity and reversible redox activity is the key to improving their performance in sodium-ion batteries (SIBs). Herein, we report a series of COFs (FPDC-TPA-COF, FPDC-TPB-COF, and FPDC-TPT-COF) based on an organosulfur linker, (trioxocyclohexane-triylidene)tris(dithiole-diylylidene))hexabenzaldehyde (FPDC). These COFs feature two-dimensional crystalline structures, high porosity, good conductivity, and densely packed redox-active sites, making them suitable for energy storage devices. Among them, FPDC-TPT-COF demonstrates a remarkably high specific capacity of 420 mAh g-1 (0.2 A g-1), excellent cycling stability (~87 % capacity retention after 3000 cycles, 1.0 A g-1) and high rate performance (339 mAh g-1 at 2.0 A g-1) as an anode for SIBs, surpassing most reported COF-based electrodes. The superior performance is attributed to the dithiole moieties enhancing the conductivity and the presence of redox-active carbonyl, imine, and triazine sites facilitating Na storage. Furthermore, the sodiation mechanism was elucidated through in situ experiments and density functional theory (DFT) calculations. This work highlights the advantages of integrating multiple functional groups into redox-active COFs for the rational design of efficient and stable SIBs.

Radical and diradical states of bis(molybdenocene dithiolene) complexes.

The synthesis and characterization of two bis(dithiolene) proligands involving heteroatomic linkers such as 1,4-dithiine and dihydro-1,4-disiline between the two protected dithiolene moieties are described. Two bimetallic complexes involving these heteroatomic bridges between two redox active bis(cyclopentadienyl)molybdenum dithiolene moieties have been synthesized and characterized by electrochemistry, spectroelectrochemistry, and their properties rationalized with (TD-)DFT. Cyclic voltammetry experiments show sequential oxidation of the two redox centers with ΔE values between successive one-electron transfers varying according to the nature of the bridge. Depending on the nature of the heteroatomic bridge, the bis-oxidized complexes exhibit either a diradical character with both radicals essentially localized on the metallacycles, or a closed-shell dicationic state.

Unusual nucleophilic reactivity of a dithiolene-based N-heterocyclic silane.

While the dithiolene-based N-heterocyclic silane (4) reacts with two equivalents of BX3 (X = Br, I) to give zwitterionic Lewis adducts 5 and 8, respectively, the parallel reaction of 4 with BCl3 results in 10, a dithiolene-substituted N-heterocyclic silane, via the Si-S bond cleavage. Unlike 5, the labile 8 may be readily converted to 9via BI3-mediated cleavage of the Si-N bond. The formation of 5 and 8 confirms that 4 uniquely possesses dual nucleophilic sites: (a) the terminal sulphur atom of the dithiolene moiety; and (b) the backbone carbon of the N-heterocyclic silane unit.

Crystal structure of histone deacetylase 6 complexed with (R)-lipoic acid, an essential cofactor in central carbon metabolism

The enzyme cofactor (R)-lipoic acid plays a critical role in central carbon metabolism due to its catalytic function in the generation of acetyl-CoA, which links glycolysis with the tricarboxylic acid cycle. This cofactor is also essential for the generation of succinyl CoA within the tricarboxylic acid cycle. However, the biological functions of (R)-lipoic acid extend beyond metabolism owing to its facile redox chemistry. Most recently, the reduced form of (R)-lipoic acid, (R)-dihydrolipoic acid, has been shown to inhibit histone deacetylases (HDACs) with selectivity for the inhibition of HDAC6. Here, we report the 2.4 Å-resolution X-ray crystal structure of the complex between (R)-dihydrolipoic acid and HDAC6 catalytic domain 2 from Danio rerio, and we report a dissociation constant (KD) of 350nM for this complex as determined by isothermal titration calorimetry. The crystal structure illuminates key affinity determinants in the enzyme active site, including thiolate-Zn2+ coordination and S-π interactions in the F583-F643 aromatic crevice. This study provides the first visualization of the connection between HDAC function and the biological response to oxidative stress: the dithiol moiety of (R)-dihydrolipoic acid can serve as a redox-regulated pharmacophore capable of simultaneously targeting the catalytic Zn2+ ion and the aromatic crevice in the active site of HDAC6.

Function of Molybdenum Insertases.

For most organisms molybdenum is essential for life as it is found in the active site of various vitally important molybdenum dependent enzymes (Mo-enzymes). Here, molybdenum is bound to a pterin derivative called molybdopterin (MPT), thus forming the molybdenum cofactor (Moco). Synthesis of Moco involves the consecutive action of numerous enzymatic reaction steps, whereby molybdenum insertases (Mo-insertases) catalyze the final maturation step, i.e., the metal insertion reaction yielding Moco. This final maturation step is subdivided into two partial reactions, each catalyzed by a distinctive Mo-insertase domain. Initially, MPT is adenylylated by the Mo-insertase G-domain, yielding MPT-AMP which is used as substrate by the E-domain. This domain catalyzes the insertion of molybdate into the MPT dithiolene moiety, leading to the formation of Moco-AMP. Finally, the Moco-AMP phosphoanhydride bond is cleaved by the E-domain to liberate Moco from its synthesizing enzyme. Thus formed, Moco is physiologically active and may be incorporated into the different Mo-enzymes or bind to carrier proteins instead.

Electronic interaction between two fluorenyl-bridged molybdenocene dithiolene electroactive centers

A bimetallic metal complex involving a fluorene linker between two redox active bis(cyclopentadienyl)molybdenum dithiolene moieties has been synthesized and characterized by electrochemistry and spectroelectrochemistry. Cyclic voltammetry experiments show sequential oxidation of the two redox centers with small ΔE values between the first and the second redox processes and between the third and the fourth ones. Comparative electrochemical studies carried out using either [NBu4][PF6] or the poorly coordinating supporting electrolyte [Na][B(C6H4(CF3)2)4] in dichloromethane indicate strong electrostatic effects on consecutive electron transfers, especially for highly charged species. Spectroelectrochemical investigations together with DFT calculations evidence that the two molybdenocene dithiolene electrophores are weakly electronically coupled through the organic bridge.

M(II) (M=Cu, Ni) Assisted C−S Bond Cleavage and Oxidative Dehydrogenation of Amine on Non‐Innocent Salen Type Ligand Platforms by Varying Nitrogen vs. Sulfur Coordination Atoms

AbstractHerein, we report two newly synthesized salen‐type ligands, 2,3‐bis((3,5‐di‐tert‐butyl‐2‐hydroxybenzyl)thio)maleonitrile (H2L1) and 2,3‐bis((3,5‐di‐tert‐butyl‐2‐hydroxybenzyl)amino)malenonitrile (H4L2), bearing different coordination sites (sulfur vs amine) at maleonitrile tethered moiety to investigate metal mediated non‐innocence chemistry of these ligands. Upon metallation, ligand H2L1 did not yield simple metal‐ligand complex, rather ligand was split into two organic fragments, dithiolene moiety (mnt)2− and phenol moiety via C−S bond cleavage wherein (mnt)2− formed a stable metal complex [M(mnt)2]2−. The C−S bond cleavage was interpreted in terms of strong p(π) … d(π) interaction between metal and dithiolene moiety in H2L1 ligand that invoked the intramolecular rearrangement facilitating C−S bond cleavage. Interestingly, the phenol moiety further transformed to either unprecedented 2,4‐di‐tert‐butyl‐6‐methylenecyclohexa‐2,4‐dienone (i. e. spiro compound; 5) or 2,4‐di‐tert‐butyl‐6‐(hydroxymethyl)phenol (6) depending on the temperature of reaction and type of metal ion used which was further predicted using DFT calculation. On the other hand, combined experimental and DFT studies explained that upon metallation, ligand H4L2 yielded non‐cleavage [M(H2L2)] (3 for M=Cu(II) and 4 for M=Ni(II) ) complex, which slowly oxidized at −NH−CH2‐(amine) region to −N=CH− (imine) in H2L2 ligand under aerobic environment via C−H bond activation, yielding [CuII(L3)] (1) (or [NiII(L3)] (2) complex (H2L3=oxidatively dehydrogenated product of H4L2 ligand.

Iron and zinc porphyrin linked MoO(dithiolene) complexes in relevance to electron transfer between Mo-cofactor and cytochrome b5 in sulfite oxidase.

Oxo-molybdenum (dithiolene) complexes covalently linked individually to iron and zinc porphyrin have been synthesized to show an electron transfer between the two metal centres in relevance to electron transfer from Mo-cofactor to cytochrome b5 domains in the oxidative half of the catalytic cycle of native sulfite oxidase. This association has been investigated by electrochemical, EPR measurement and X-ray absorbance spectroscopy techniques.

A New Inhibitor of ADAM17 Composed of a Zinc-Binding Dithiol Moiety and a Specificity Pocket-Binding Appendage.

A disintegrin and metalloproteinase 17 (ADAM17) is a zinc-dependent enzyme that catalyzes the cleavage of the extracellular domains of various transmembrane proteins. ADAM17 is regarded as a promising drug target for the suppression of various diseases, including cancer metastasis. We synthesized a new ADAM17 inhibitor, SN-4, composed of a zinc-binding dithiol moiety and an appendage that specifically binds to a pocket of ADAM17. We show that SN-4 inhibits the ability of ADAM17 to cleave tumor necrosis factor α (TNF-α) in vitro. This activity was reduced by the addition of zinc, indicating the importance of the zinc chelating dithiol moiety. Inhibition of TNF-α cleavage by SN-4 in cells was also observed, and with an IC50 of 3.22 µM, SN-4 showed slightly higher activity than the well-studied ADAM17 inhibitor marimastat. Furthermore, SN-4 was shown to inhibit cleavage of CD44 by ADAM17, but not by ADAM10, and to suppress cell invasion. Molecular docking showed good fitting of the specificity pocket-binding group and one SH of SN-4 and hinted at possible means of structural optimization. This study provides clues for the development of potent and selective ADAM17 inhibitors.

Hydrogen Evolving Activity of Dithiolene-Based Metal-Organic Frameworks with Mixed Cobalt and Iron Centers.

Electrocatalytic systems based on metal-organic frameworks (MOFs) have attracted great attention due to their potential application in commercially viable renewable energy-converting devices. We have recently shown that the cobalt 2,3,6,7,10,11-triphenylenehexathiolate (CoTHT) framework can catalyze the hydrogen evolution reaction (HER) in fully aqueous media with Tafel slopes as low as 71 mV/dec and near-unity Faradaic efficiency (FE). Taking advantage of the high synthetic tunability of MOFs, here, we synthesize a series of iron and mixed iron/cobalt THT-based MOFs. The incorporation of the iron and cobalt dithiolene moieties is verified by various spectroscopic techniques, and the integrity of the crystalline structure is maintained regardless of the stoichiometries of the two metals. The hydrogen evolving activity of the materials was explored in pH 1.3 aqueous electrolyte solutions. Unlike CoTHT, the FeTHT framework exhibits minimal activity due to a late catalytic onset [-0.440 V versus reversible hydrogen electrode (RHE)] and a large Tafel slope (210 mV/dec). The performance of the mixed-metal MOFs is adversely affected by the incorporation of Fe, where increasing Fe content results in MOFs with lower HER activity and diminished long-term stability and FE for H2 production. It is proposed that the FeTHT domains undergo alternative Faradaic processes under catalytic conditions, which alter its local structure and electrochemical behavior, eventually resulting in a material with diminished HER performance.

Bioconjugation of Cyclometalated Gold(III) Lipoic Acid Fragments to Linear and Cyclic Breast Cancer Targeting Peptides.

Cell-targeting peptides (CTPs) are increasingly used in the field of cancer research due to their high affinity and specificity to cell or tissue targets. In the search for novel metal-based drug candidates, our research group is particularly focused on bioconjugates by utilizing peptides to increase the selectivity of cytotoxic organometallic compounds. Motivated by the relatively high cytotoxic activity of gold complexes, such as Auranofin (approved to treat rheumatoid arthritis), for the treatment of various diseases, we anticipated that gold peptide bioconjugates would present interesting candidates for novel breast cancer therapies. For this, we investigate the use of the natural compound lipoic acid (Lpa) as a bioconjugation handle to link Au complexes in the oxidation state +III to peptides using the dithiol moiety. Using this strategy, we have synthesized Au(III) complex bioconjugates linked to the linear LTVSPWY peptide and two cyclic DfKRG and KTTHWGFTLG tumor-targeting peptides. Solid-phase peptide synthesis (SPPS) was used to prepare the peptides, with lipoic acid introduced N-terminally as a conjugation handle. After peptide cleavage, the metal complex was introduced in solution by first reducing the internal disulfide bond, followed by reaction with Au(ppy)Cl2 (1, ppy: 2-phenyl-pyridine), to yield the Au(III)-Lpa-peptide bioconjugates. The new bioconjugates were successfully synthesized, purified by semi-preparative HPLC, and characterized by ESI-MS. Au(III)-peptide bioconjugates were tested as cytotoxic agents against two different human breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human fibroblasts cells (GM5657T) and compared to cisplatin, the parent Au(III) dichloride complex, and metal-free peptides. These in vitro data show that the Au(III)-peptide bioconjugate 5, possessing the cyclic integrin-targeting RGD-derived peptide sequence in the structure, exhibits improved activity compared to the parent gold(III) compound Au(ppy)Cl2 (1) as well as to cisplatin or the metal-free peptide. Moreover, the excellent targeting properties of 5 are supported by the fact that a Au(III)-peptide conjugate with the exact same peptide sequence, but a linear rather than the cyclic form of 5 exhibits 10 times lower cytotoxic activity.

Cation‐anion radical interactions between halopyridinium cations and metal dithiolene complexes [M(C2S2)2CN]−•: A theoretical study of halogen bonds in conducting or magnetic molecular materials

AbstractMetal dithiolene complexes have been extensively used for the elaboration of conducting or magnetic materials, whose molecular arrangements can be sensitively influenced by strong and directional noncovalent interactions. In this work, halogen bonds between N‐methyl‐3‐halopyridinium cations and cyano‐substituted anion radicals, [M(C2S2)2CN]−• (M = Ni, Pd, and Pt), were systematically investigated at the M06 level of theory. The CN···X interactions in these systems are predicted to be considerably strong and play a vital role in the controlling of the crystal structures of molecular conductors and magnets. The electrostatics contributes mainly to the attraction of these halogen bonds, while the orbital interaction is also important. Particularly, the formation of these interactions has little effect on the distribution of SOMOs, which is strongly delocalized on the two dithiolene moieties. These results will assist in the design of functional materials that exhibit exotic conducting or magnetic properties.

Localization versus Delocalization in Chiral Single Component Conductors of Gold Bis(dithiolene) Complexes.

The first examples of chiral single component conductors are reported. Both (S,S) and (R,R) enantiomers of 5,6-dimethyl-5,6-dihydro-1,4-dithiin-2,3-dithiolate (dm-dddt) ligand have been used to prepare anionic metal bis(dithiolene) complexes formulated as ([(n-Bu)4N][M(dm-dddt)2] (M = Au, Ni), which are isostructural according to single crystal X-ray analysis. Single crystal transport measurements indicate semiconducting behavior for the anionic radical Ni complexes, with low room temperature conductivity values and high activation energies. Electrocrystallization experiments provided neutral [M(dm-dddt)2] (M = Au, Ni) complexes. The neutral radical gold compounds show intermolecular S···S interactions in the solid state giving rise to layers interconnected through weak C-H···S hydrogen bonds. The most peculiar structural feature concerns a dissymmetry between the two dithiolene moieties, while the nickel counterpart is symmetric. Single crystal resistivity measurements show thermally activated behavior for the open-shell gold complexes, with room temperature conductivity values of 0.02-0.04 S·cm(-1) and activation energies strongly influenced by hydrostatic pressure. A thorough theoretical study on nickel anion radical and gold neutral radical bis(dithiolene) complexes applied to the chiral complexes [M(dm-dddt)2] (M = Au, Ni(-)) and to a series of previously reported compounds addressed the issue of symmetry versus asymmetry from an electronic coupling perspective between the two dithiolene ligands. It results that neutral gold complexes with dithiolene ligands without extended delocalization are Class II mixed-valent compounds in the Robin and Day classification, presenting an inherent tendency toward asymmetric structures, which can be however modulated by the intermolecular organization in the solid state.

Scorpionate Complexes as Models for Molybdenum Enzymes

Scorpionate ligands have supported the development of a number of important synthetic models for pterin‐containing molybdenum enzymes. These ligands stabilize biologically relevant mononuclear oxido‐ and sulfido‐Mo(VI,V,IV) complexes capable of sustaining a wide range of biomimetic reactions, including oxygen atom, sulfur atom and coupled electron‐proton transfer reactions. Studies of scorpionate‐Mo compounds have also provided key insights into the bonding in oxido‐Mo dithiolene moieties, the orbital control of enzymatic reactions and the synthesis and behavior of biologically relevant Mo‐pterindithiolene complexes. This microreview covers advances in the synthesis and study of scorpionate complexes as models for molybdenum enzymes in the second half of the field's 30‐year history, i.e., from around 2000, the turn of the century, onwards.

Synthesis and Reactivity of a Bio-inspired Dithiolene Ligand and its Mo Oxo Complex.

An original synthesis of the fused pyranoquinoxaline dithiolene ligand qpdt(2-) is discussed in detail. The most intriguing step is the introduction of the dithiolene moiety by Pd-catalyzed carbon-sulfur coupling. The corresponding Mo(IV)O complex (Bu4N)2 [MoO(qpdt)2] (2) underwent reversible protonation in a strongly acidic medium and remained stable under anaerobic conditions. Besides, 2 was found to be very sensitive towards oxygen, as upon oxidation it formed a planar dithiin derivative. Moreover, the qpdt(2-) ligand in the presence of [MoCl4 (tBuNC)2] formed a tetracyclic structure. The products resulting from the unique reactivity of qpdt(2-) were characterized by X-ray diffraction, mass spectrometry, NMR spectroscopy, UV/Vis spectroscopy, and electrochemistry. Plausible mechanisms for the formation of these products are also proposed.

Designing the Molybdopterin Core through Regioselective Coupling of Building Blocks.

Molybdopterin is an essential cofactor for all forms of life. The cofactor is composed of a pterin moiety appended to a dithiolene-functionalized pyran ring, and through the dithiolene moiety it binds metal ions. Different synthetic strategies for dithiolene-functionalized pyran precursors that have been designed and synthesized are discussed. These precursors also harbor 1,2-diketone or osone functionality that has been condensed with 1,2-diaminobenzene or other heterocycles resulting in several quinoxaline or pterin derivatives. Use of additives improves the regioselectivity of the complexes. The molecules have been characterized by (1)H and (13)C NMR and IR spectroscopies, as well as by mass spectrometry. In addition, several compounds have been crystallographically characterized. The geometries of the synthesized molecules are more planar than the geometry of the cofactor found in proteins.

Redox-active ferrocene-dithiolenes hybrid complexes showing switchable nonlinear optical properties

Density functional theory(DFT) calculations were carried out to investigate the geometry structures, redox properties and second-order nonlinear optical(NLO) properties of ferrocene(Fc)-dithiolenes hybrid complexes. The switchable second-order NLO properties of these complexes are induced by the redox process. The oxidized process significantly affects the geometrical structures of the dithiolene moieties, that is, the embowed dithiolene moieties change into planar structures. It supports that the dithiolene moieties are the oxidized center. The βtot values of the cationic species are at least 4 and 10 times those of their corresponding parent complexes, respectively. Further, the time-dependent DFT calculation illustrates that the low-energy absorption(which is helpful for the large NLO response) is mainly assigned to intra-ligand charge transfer [π(ex-dithiolene)→π*(ex-dithiolene)]. These results suggest the potential use of the novel Fc-based dithiolenes complexes as versatile and fascinating NLO switching materials.

On the Critical Effect of the Metal (Mo vs. W) on the [3+2] Cycloaddition Reaction of M3 S4 Clusters with Alkynes: Insights from Experiment and Theory.

Whereas the cluster [Mo3 S4 (acac)3 (py)3 ](+) ([1](+) , acac=acetylacetonate, py=pyridine) reacts with a variety of alkynes, the cluster [W3 S4 (acac)3 (py)3 ](+) ([2](+) ) remains unaffected under the same conditions. The reactions of cluster [1](+) show polyphasic kinetics, and in all cases clusters bearing a bridging dithiolene moiety are formed in the first step through the concerted [3+2] cycloaddition between the C≡C atoms of the alkyne and a Mo(μ-S)2 moiety of the cluster. A computational study has been conducted to analyze the effect of the metal on these concerted [3+2] cycloaddition reactions. The calculations suggest that the reactions of cluster [2](+) with alkynes feature ΔG(≠) values only slightly larger than its molybdenum analogue, however, the differences in the reaction free energies between both metal clusters and the same alkyne reach up to approximately 10 kcal mol(-1) , therefore indicating that the differences in the reactivity are essentially thermodynamic. The activation strain model (ASM) has been used to get more insights into the critical effect of the metal center in these cycloadditions, and the results reveal that the change in reactivity is entirely explained on the basis of the differences in the interaction energies Eint between the cluster and the alkyne. Further decomposition of the Eint values through the localized molecular orbital-energy decomposition analysis (LMO-EDA) indicates that substitution of the Mo atoms in cluster [1](+) by W induces changes in the electronic structure of the cluster that result in weaker intra- and inter-fragment orbital interactions.

Silicon-Heteroaromatic [FeFe] hydrogenase model complexes: insight into protonation, electrochemical properties, and molecular structures.

To learn from Nature how to create an efficient hydrogen-producing catalyst, much attention has been paid to the investigation of structural and functional biomimics of the active site of [FeFe]-hydrogenase. To understand their catalytic activities, the μ-S atoms of the dithiolate bridge have been considered as possible basic sites during the catalytic processes. For this reason, a series of [FeFe]-H2 ase mimics have been synthesized and characterized. Different [FeFe]-hydrogenase model complexes containing bulky Si-heteroaromatic systems or fluorene directly attached to the dithiolate moiety as well as their mono-PPh3 -substituted derivatives have been prepared and investigated in detail by spectroscopic, electrochemical, X-ray diffraction, and computational methods. The assembly of the herein reported series of complexes shows that the μ-S atoms can be a favored basic site in the catalytic process. Small changes in the (hetero)-aromatic system of the dithiolate moiety are responsible for large differences in their structures. This was elucidated in detail by DFT calculations, which were consistent with the experimental results.