DNA structural distortions induced by ruthenium-arene anticancer compounds

Organometallic ruthenium(II)-arene (RA) compounds combine a rich structural diversity with the potential to overcome existing chemotherapeutic limitations. In particular, the two classes of compounds [Ru(II)(eta(6)-arene)X(en)] and [Ru(II)(eta(6)-arene)(X)2(pta)] (RA-en and RA-pta, respectively; X = leaving group, en = ethylenediamine, pta = 1,3,5-triaza-7-phosphaadamantane) have become the focus of recent anticancer research. In vitro and in vivo studies have shown that they exhibit promising new activity profiles, for which their interactions with DNA are suspected to be a crucial factor. In the present study, we investigate the binding processes of monofunctional RA-en and bifunctional RA-pta to double-stranded DNA and characterize the resulting structural perturbations by means of ab initio and classical molecular dynamics simulations. We find that both RA complexes bind easily through their ruthenium center to the N7 atom of guanine bases. The high flexibility of DNA allows for fast accommodation of the ruthenium complexes into the major groove. Once bound to the host, however, the two complexes induce different DNA structural distortions. Strain induced in the DNA backbone from RA-en complexation is released by a local break of a Watson-Crick base-pair, consistent with the experimentally observed local denaturation. The bulkier RA-pta, on the other hand, bends the DNA helix toward its major groove, resembling the characteristic DNA distortion induced by the classic anticancer drug cisplatin. The atomistic details of the interactions of RA complexes with DNA gained in the present study shed light on some of the anticancer properties of these compounds and should assist future rational compound design.     

Analysis of solid-supported oligonucleotides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

This study presents matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) as a powerful tool to analyze and characterize oligonucleotides covalently linked to a solid support during their synthesis. The analysis of the fragment ions generated either in negative or positive mode allows direct and easy access to the nucleotide sequence and identification of the internucleosidic linkage. The mechanisms of the fragmentation of the solid-supported oligonucleotides induced by MALDI-TOFMS are discussed. Copyright 2000 John Wiley & Sons, Ltd.     

Facilitating access to the most easily ionized molecule: an improved synthesis of the key intermediate, W2(hpp)4Cl2, and related compounds

A far superior synthesis is reported for W(2)(hpp)(4)Cl(2), a key intermediate in the synthesis of the most easily ionized closed-shell molecule W(2)(hpp)(4) (hpp = the anion of the bicyclic guanidine compound 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine). At 200 degrees C, the one-pot reaction of the air-stable and commercially available compounds W(CO)(6) and Hhpp in o-dichlorobenzene produces W(2)(hpp)(4)Cl(2) in multigram quantities with isolated yields of over 90%. At lower temperatures, the reaction can lead to other compounds such as W(Hhpp)(2)(CO)(4) or W(2)(mu-CO)(2)(mu-hpp)(2)(eta(2)-hpp)(2), which are isolable in good purity depending upon the specific conditions employed. These compounds provide insight into the reaction pathway to W(2)(hpp)(4)Cl(2) and W(2)(hpp)(4). Two additional derivatives, W(2)(hpp)(4)X(2) where X is PF(6)(-) or the anion tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB), have also been synthesized and structurally characterized. A comparison of the electrode potentials of W(2)(mu-CO)(2)(mu-hpp)(2)(eta(2)-hpp)(2) and the di-p-anisylformamidinate analogue shows that oxidation of the hpp compound is significantly displaced (1.12 V) and shows that the bicyclic guanidinate ligand is considerably better than the formamidinate anion at stabilizing high oxidation states. A differential pulse voltammogram of W(2)(hpp)(4)(TFPB)(2) in THF shows two reduction processes with an E(1/2) of -0.97 V for the first and -1.81 V (vs Ag/AgCl) for the second. DFT calculations on the W(2)(hpp)(4)(2+) units in W(2)(hpp)(4)X(2) compounds show that the metal-metal bonding orbitals are destabilized by the axial ligands, which accounts for significant variations in the W-W distances. The low-energy gas-phase ionizations of W(2)(hpp)(4) are also reported and discussed.     

Enhancement of the biochemical activity of some market antibiotics by chemical modification: Synthesis,characterization, and biochemical evaluation

The reaction of isatin with the Ampicillin gave the new compound: (6R)‐3,3‐dimethyl‐7‐oxo‐6‐(2‐(([E]‐2‐oxoindolin‐3‐ylidene)amino)‐2‐phenylacetamido)‐4‐thia‐1‐azabicyclo[3.2.0]hept ‐ane‐2‐carboxylic acid (HAI). The new complexes derived from HAI and Co(II), Ni(II), Cu(II), Eu(III), and Gd(III) were obtained in pure form. The obtained compounds were characterized by elemental analysis, FTIR, UV–Vis, Fluorescence, ¹HNMR, Mass spectra, DTA, TGA, Magnetic susceptibility, X‐ray, AAS, and the conductivity of 0.001 M in DMSO. The obtained data indicated the formation of the target complexes: [Co(HAI)(H₂O)(NO₃)]NO₃.4H₂O, [Ni(AI)(H₂O)₂]Cl.2H₂O, [Cu(AI)]Cl.H₂O, [Eu(AI)(H₂O)Cl]Cl.5H₂O and [Gd(AI)(H₂O)(NO₃)]NO₃.3H₂O. The ligation sites were predicted from the guide of the FTIR and thermal analysis meanwhile the stereochemistry was proved by the UV–Vis and magnetic moment. Co(II) and Ni(II) gave an octahedral structure while Cu(II) gave a square planar form. Molecular modeling, molecular mechanics, and DFT calculations were carried out for the synthesized compounds. The active lone pair and surface properties were obtained and discussed in the silico level. The x‐ray analysis indicates the nanoparticle behavior of the Cu‐AI complex with a monoclinic structure. The interactions of the synthesized complexes with FM‐DNA moiety were investigated through spectrometric titration (UV–vis. spectra) and by using fluorescence spectroscopy. The modes and binding affinities were evaluated and discussed using Benesi–Hildebrand method. Antimicrobial activities of the synthesized compounds have been screened using the disc diffusion method. HAI and Cu‐AI gave activity exceeded the Ampicillin. The docking work was carried using the targeting protein of Escherichia coli FabH (PDB code: 1HNJ). The obtained binding energy was compared and discussed in terms of the in vitro studies.     

Synthesis and binding studies of Alzheimer ligands on solid support

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.     

Selectivity analysis of 5-(arylthio)-2,4-diaminoquinazolines as inhibitors of Candida albicans dihydrofolate reductase by molecular dynamics simulations

A series of 5-(arylthio)-2,4-diaminoquinazolines are known as selective inhibitors of dihydrofolate reductase (DHFR) from Candida albicans. We have performed docking and molecular dynamics simulations of these inhibitors with C. albicans and human DHFR to understand the basis for selectivity of these agents. Study was performed on a selected set of 10 compounds with variation in structure and activity. Molecular dynamics simulations were performed at 300 K for 45 ps with equilibration for 10 ps. Trajectory data was analyzed on the basis of hydrogen bond interactions, energy of binding and conformational energy difference. The results indicate that hydrogen bonds formed between the compound and the active site residues are responsible for inhibition and higher potency. The selectivity index, i.e the ratio of I₅₀ against human DHFR to I₅₀ against fungal DHFR, is mainly determined by the conformation adapted by the compounds within the active site of two enzymes. Since the human DHFR active site is rigid, the compound is trapped in a higher energy conformation. This energy difference between the two conformations E mainly governs the selectivity against fungal DHFR. The information generated from this analysis of potency and selectivity should be useful for further work in the area of antifungal research.     

Characterization of silsesquioxanes by size-exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Liquid chromatography in combination with spectroscopic methods like matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) or nuclear magnetic resonance (NMR) spectroscopy is a powerful method to characterize silsesquioxanes and silsesquioxane mixtures. As new examples, the formation of silsesquioxyl-substituted silsesquioxanes [(n-octyl)(7)(SiO(1.5))(8)](2)O and [(n-octyl)(7)(SiO(1.5))(8)O](2)[(n-octyl)(6)(SiO(1.5))(8)] as well as the cage rearrangement of octa-[(n-heptyl)silsesquioxane] to larger structures [(n-heptyl)SiO(1.5))](n) up to n=28 are shown.     

Sample preparation for high throughput accurate mass analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

An automated sample preparation for high throughput accurate mass determinations by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been developed. Sample preparation was performed with an automated workstation and automated mass analyses were performed with a commercial MALDI-TOF mass spectrometer. The method was tested with a 41-sample library. MALDI-TOFMS was found to give the needed sensitivity, accurate mass measurement, and soft ionization necessary for structure confirmation, even of mixtures. A mass accuracy of 5 ppm or less was obtained in over 80% of known compound measurements. A mass accuracy better than 10 ppm was obtained for all measurements of known compounds. Analyses of parallel synthesis products resulted in 77% of the measurements with a mass accuracy of 5 ppm or better.     

Ligand-directed acyl imidazole chemistry for labeling of membrane-bound proteins on live cells

Chemistry-based protein labeling in living cells is undoubtedly useful for understanding natural protein functions and for biological/pharmaceutical applications. Here, we report a novel approach for endogenous membrane-bound protein labeling for both in vitro and live cell conditions. A moderately reactive alkyloxyacyl imidazole (AI) assisted by ligand-binding affinity (ligand-directed AI (LDAI)) chemistry allowed us to selectively modify natural proteins, such as dihydrofolate reductase (DHFR) and folate receptor (FR), neither of which could be efficiently labeled using the recently developed ligand-directed tosylate approach. It was clear that LDAI selectively labeled a single Lys(K32) in DHFR, proximal to the ligand-binding pocket. We also demonstrate that the fluorescein-labeled (endogenous, by LDAI) FR works as a fluorescent biosensor on the live KB cell surface, which allowed us to carry out unprecedented in situ kinetic analysis of ligand binding to FR.     

Intramolecularly coordinated heteroleptic organostannylene tungsten pentacarbonyl complexes 4-tBu-2,6-[P(O)(OiPr)2]2C6H2Sn(X)W(CO)5 (X = Cl, F, PPh2, PPh2[W(CO)5]). Syntheses and reactivity

The synthesis of the intramolecularly coordinated heteroleptic organostannylene tungsten pentacarbonyl complexes 4-tBu-2,6-[P(O)(OiPr)(2)](2)C(6)H(2)Sn(X)W(CO)(5) (1, X = Cl; 2, X = F; 3, X = PPh(2)) and of 4-tBu-2,6-[P(O)(OiPr)(2)](2)C(6)H(2)Sn[W(CO)(5)]PPh(2)[W(CO)(5)], 4, are reported. UV-irradiation of compound 4 in tetrahydrofurane serendipitously gave the bis(organostannylene) tungsten tetracarbonyl complex cyclo-O(2)W[OSn(R)](2)W(CO)(4) (R = 4-tBu-2,6-[P(O)(OiPr)(2)](2)C(6)H(2)), 5, that contains an unprecedented W(0)-Sn-O-W(vi) bond sequence. The compounds 1-5 were characterized by means of single crystal X-ray diffraction analysis, (1)H, (13)C, (19)F, (31)P, (119)Sn NMR, and IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and elemental analysis. Compound 4 features a hindered rotation about the Sn-P bond.     

Ruthenium bipyridyl compounds with two terminal alkynyl ligands

Compounds of the form Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)2(X2bipy = 4,4'-X(2)-2,2'-bipyridine, X = Me 3a, Br 3b, I 3c) have been synthesised from the mono-alkynyl precursors Ru(X2bipy)(PPh3)2(-C triple bond CC6H4NO2-p)Cl (X = Me 2a, Br 2b, I 2c); the former are the first ruthenium bis-alkynyl compounds that also contain a bipyridyl ligand. Spectroelectrochemical investigation of 3a shows that the metal is readily oxidised to form the ruthenium(III) compound 3a+, and will also undergo a single-electron reduction at each nitro group to form 3a2-. ESR and UV/visible spectra of these redox congeners are presented. We also report the synthesis of [Ru(Me2bipy)(PPh3)2(-C triple bond CBut)(N triple bond N)][PF6] during the attempted synthesis of Ru(Me2bipy)(PPh3)2(-C triple bond CBut)2, and report its X-ray crystal structure and IR spectrum. X-Ray crystal structures of 3b and 3c(as two different solvates) are presented, and the nature of the intermolecular interactions seen therein is discussed. Z-Scan measurements on Ru(Me2bipy)(PPh3)2(-C triple bond CR)Cl (R = C6H4NO2-p2a, But, Ph, C6H4Me) are also reported, and show that Ru(Me2bipy)(PPh3)2(-C triple bond CR)Cl (R = C6H4NO2-p2a, Ph) exhibit moderate third-order non-linearities.     

Allopurinol- and Hypoxanthine-Copper(II) Compounds. Spectral and Magnetic Studies of Novel Dinuclear Coordination Compounds with Bridging Hypoxanthine

The synthesis in aqueous solution and pH = 1.0 of several novel Cu(II) compounds with allopurinol and hypoxanthine as heterocyclic ligands and X = Cl(-), Br(-), NO(3)(-), SO(4)(2-), and ClO(4)(-) as anions, together with their spectral and magnetic characterization, is reported. The studies of the Cu(II) systems with these heterocycles and Cl(-) or Br(-) support their Cu(II)(L)(2)(X)(2) character and their interactions through halogen atoms as bridging ligands, leading to a very weak antiferromagnetic coupling. For the Cu(II) compounds with hypoxanthine and X = NO(3)(-), SO(4)(-), or ClO(4)(-), new examples of the cupric acetate type are obtained, showing in all cases similar strong antiferromagnetic coupling. These three cases are new examples of the scarce Cu(II) dinuclear compounds with bridging hypoxanthine which have been reported up to now.     

Retrosynthetic accessibility score (RAscore) – rapid machine learned synthesizability classification from AI driven retrosynthetic planning

Computer aided synthesis planning (CASP) is part of a suite of artificial intelligence (AI) based tools that are able to propose synthesis routes to a wide range of compounds. However, at present they are too slow to be used to screen the synthetic feasibility of millions of generated or enumerated compounds before identification of potential bioactivity by virtual screening (VS) workflows. Herein we report a machine learning (ML) based method capable of classifying whether a synthetic route can be identified for a particular compound or not by the CASP tool AiZynthFinder. The resulting ML models return a retrosynthetic accessibility score (RAscore) of any molecule of interest, and computes at least 4500 times faster than retrosynthetic analysis performed by the underlying CASP tool. The RAscore should be useful for pre-screening millions of virtual molecules from enumerated databases or generative models for synthetic accessibility and produce higher quality databases for virtual screening of biological activity.

The retrosynthetic accessibility score (RAscore) is based on AI driven retrosynthetic planning, and is useful for rapid scoring of synthetic feasability and pre-screening of large datasets of virtual/generated molecules.     

Computer-aided drug design: A free energy perturbation study on the binding of methyl-substituted pterins and N5-deazapterins to dihydrofolate reductase

Summary Molecular dynamics simulation and free energy perturbation techniques have been used to study the relative binding free energies of 8-methylpterins and 8-methyl-N5-deazapterins to dihydrofolate reductase (DHFR). Methyl-substitution at the 5, 6 and 7 positions in the N-heterocyclic ring gives rise to a variety of ring substituent patterns and biological activity: several of these methyl derivatives of the 8-methyl parent compounds (8-methylpterin and 8-methyl-N5-deazapterin) have been identified as substrates or inhibitors of vertebrate DHFR in previous work. The calculated free energy differences reveal that the methyl-substituted compounds are thermodynamically more stable than the primary compounds (8-methylpterin and 8-methyl-N5-deazapterin) when bound to the enzyme, due largely to hydrophobic hydration phenomena. Methyl substitution at the 5 and/or 7 positions in the 6-methyl-substituted compounds has only a small effect on the stability of ligand binding. Furthermore, repulsive interactions between the 6-methyl substituent and DHFR are minimal, suggesting that the 6-methyl position is optimal for binding. The results also show that similarly substituted 8-methylpterins and 8-methyl-N5-deazapterins have very similar affinities for binding to DHFR. The computer simulation predictions are in broad agreement with experimental data obtained from kinetic studies, i.e. 6,8-dimethylpterin is a more efficient substrate than 8-methylpterin and 6,8-dimethyl-N5-deazapterin is a better inhibitor than 8-methyl-N5-deazapterin.     

Synthesis and characterization of Ru2(DMBA)4X2 (X = CN, N3, N(CN)2, I): controlling structural, redox, and magnetic properties with axial ligands

Metathesis reactions between Ru(2)(DMBA)(4)Cl(2) (DMBA = N,N'-dimethylbenzamidinate) and MX (M = Na and K) yielded bis-adduct derivatives Ru(2)(DMBA)(4)X(2) (X = CN (1), N(3) (2), N(CN)(2) (3)). Metathesis reactions between Ru(2)(DMBA)(4)(NO(3))(2) and KI resulted in Ru(2)(DMBA)(4)I(2) (4). Compound 1 is diamagnetic, while compounds 2-4 are paramagnetic (S = 1). Both compounds 1 and 2 undergo two reversible one-electron processes, an oxidation and a reduction, while compound 3 features a quasireversible reduction. Single-crystal X-ray diffraction studies revealed that the Ru-Ru bond lengths are 2.4508(9), 2.3166(7), 2.304[1], and 2.328(1) A for compounds 1-4, respectively. Structural and electrochemical data clearly indicate that the axial ligands impart a significant influence on the electronic structures of diruthenium species.     

Deep Learning and Structure-Based Virtual Screening for Drug Discovery against NEK7: A Novel Target for the Treatment of Cancer

NIMA-related kinase7 (NEK7) plays a multifunctional role in cell division and NLRP3 inflammasone activation. A typical expression or any mutation in the genetic makeup of NEK7 leads to the development of cancer malignancies and fatal inflammatory disease, i.e., breast cancer, non-small cell lung cancer, gout, rheumatoid arthritis, and liver cirrhosis. Therefore, NEK7 is a promising target for drug development against various cancer malignancies. The combination of drug repurposing and structure-based virtual screening of large libraries of compounds has dramatically improved the development of anticancer drugs. The current study focused on the virtual screening of 1200 benzene sulphonamide derivatives retrieved from the PubChem database by selecting and docking validation of the crystal structure of NEK7 protein (PDB ID: 2WQN). The compounds library was subjected to virtual screening using Auto Dock Vina. The binding energies of screened compounds were compared to standard Dabrafenib. In particular, compound 762 exhibited excellent binding energy of −42.67 kJ/mol, better than Dabrafenib (−33.89 kJ/mol). Selected drug candidates showed a reactive profile that was comparable to standard Dabrafenib. To characterize the stability of protein–ligand complexes, molecular dynamic simulations were performed, providing insight into the molecular interactions. The NEK7–Dabrafenib complex showed stability throughout the simulated trajectory. In addition, binding affinities, pIC50, and ADMET profiles of drug candidates were predicted using deep learning models. Deep learning models predicted the binding affinity of compound 762 best among all derivatives, which supports the findings of virtual screening. These findings suggest that top hits can serve as potential inhibitors of NEK7. Moreover, it is recommended to explore the inhibitory potential of identified hits compounds through in-vitro and in-vivo approaches.     

Design,synthesis and biological evaluation of antimalarial activity of new derivatives of 2,4,6-<Emphasis Type="Italic">s</Emphasis>-triazine

Dihydrofolate reductase (DHFR) is an important enzyme for de novo synthesis of nucleotides in Plasmodium falciparum and it is essential for cell proliferation. DHFR is a well known antimalarial target for drugs like cycloguanil and pyrimethamine which target its inhibition for their pharmacological actions. However, the clinical efficacies of these antimalarial drugs have been compromising due to multiple mutations occurring in DHFR that lead to drug resistance. In this background, we have designed 22 s -triazine compounds using the best five parameters based 3D-QSAR model built by using genetic function approximation. In-silico designed compounds were further filtered to 6 compounds based upon their ADME properties, docking studies and predicted minimum inhibitory concentrations (MIC). Out of 6 compounds, 3 compounds were synthesized in good yield over 95% and characterized using IR, ¹HNMR, ¹³CNMR and mass spectroscopic techniques. Parasitemia inhibition assay was used to evaluate the antimalarial activity of s -triazine compounds against 3D7 strain of P. falciparum. All the three compounds (7, 13 and 18) showed 30 times higher potency than cycloguanil (standard drug). It was observed that compound 18 was the most active while the compound 13 was the least active. On the closer inspection of physicochemical properties and SAR, it was observed that the presence of electron donating groups, number of hydrogen bond formation, lipophilicity of ligands and coulson charge of nitrogen atom present in the triazine ring enhances the DHFR inhibition significantly. This study will contribute to further endeavours of more potent DHFR inhibitors.     

Carboxylate and alkyl carbonate coordination at the hydrophobic binding site of redox-active dicobalt amine thiophenolate complexes

A series of new dicobalt complexes of the permethylated macrocyclic hexaamine dithiophenolate ligand H(2)L(Me) have been prepared and investigated in the context of ligand binding and oxidation state changes. The octadentate ligand is an effective dinucleating ligand that supports the formation of bioctahedral complexes with a central N(3)Co(mu-SR)(2)(mu-X)CoN(3) core structure, leaving a free bridging position X for the coordination of the substrates. The acetato- and cinnamato-bridged complexes [(L(Me))Co(II)(2)(mu-O(2)CMe)](+) (2) and [(L(Me))Co(II)(2)(mu-O(2)CCH=CHPh)](+) (5) were prepared by reaction of the mu-Cl complex [(L(Me))Co(II)(2)(mu-Cl)](+) (1) with the corresponding sodium carboxylates in methanol. The electrochemical properties of these and of the methyl carbonate complex [(L(Me))Co(II)(2)(mu-O(2)COMe)](+) (8) were also investigated. All complexes undergo two stepwise oxidations at ca. E(1)(1/2) = +0.22 and at E(2)(1/2) = ca. +0.60 V vs SCE, affording the mixed-valent complexes [(L(Me))Co(II)Co(III)(mu-O(2)CR)](2+) (3, 6, 9) and the fully oxidized Co(III)Co(III) forms [(L(Me))Co(III)(2)(mu-O(2)CR)](3+) (4, 7, 10), respectively. Compounds 3, 6, 9 and 4, 7, 10 refer to acetato-, cinnamato-, and methylcarbonato species, respectively. The Co(II)Co(III) compounds were prepared by comproportionation of the respective Co(II)(2) and Co(III)(2) compounds. The Co(III)Co(III) species were prepared by bromine oxidation of the Co(II)Co(II) forms. The crystal structures of complexes 2.BPh(4).MeCN, 3.(I(3))(2), 5.BPh(4).2MeCN, 6.(ClO(4))(2).EtOH, 7.(ClO(4))(3).MeCN.(H(2)O)(3), and 9.(ClO(4))(2).(MeOH)(2).H(2)O were determined by single-crystal X-ray crystallography at 210 K. The oxidations occur without gross structural changes of the parent complexes. The Co(II)Co(III) complexes are composed of high-spin Co(II) (d(7)) and low-spin Co(III) (d(6)) ions. The Co(III)Co(III) complexes are diamagnetic. The oxidation reactions affect the binding mode of the substrates. In the Co(II)(2) and Co(II)Co(III) forms the carboxylates bridge the two Co(2+) ions in a symmetric mu-1,3 fashion with uniform C-O bond distances, whereas asymmetric bridging modes, with one short C=O and one long C-O distance, are adopted in the fully oxidized species. This is consistent with the observed shifts in vibrational frequencies for nu(as)(C-O) and nu(s)(C-O) across the series.