Isomeric Ligands Research Articles

First report on the investigation of the pH dependent behavior in the complexes of palladium(II) acetylacetonate with isomers of dinitrobenzoate: Combined single crystal X-ray diffraction and Hirshfeld surface calculations

The novel six palladium acetylacetonate [Pd(acac)2] and isomers of dinitrobenzoate anions (e.g., 3,5-dinitrobenzoate (L1) and 2,4-dinitrobenzoate (L2)) based complexes (1-6) have been synthesized via a facile hydrothermal route. These complexes are further characterized by single crystal X-ray diffraction (SCXRD), IR spectroscopy, NMR spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy, and thermogravimetric analysis (TGA). For the synthesis of these complexes, the initial precursors of isomers of dinitrobenzoates, i.e., 3,5 dinitrobenzoic acid (L1H) and 2,4 dinitrobenzoic acid (L2H) have been used at different pH conditions. The study evaluates the ability of the acetylacetonate group to act as a hydrogen bond acceptor in the presence of isomeric dinitrobenzoate ligands. The basic structure of Pd(acac)2 undergoes changes due to the varying chemical environment at different pH conditions. At lower pH levels, protonation of the acac group has occurred (e.g., complex 1), leading to changes in the coordination environment around the Pd(II) center. At the slightly basic pH value (⁓10), one of the acac anion is replaced with two ammonia molecules (e.g., complex 2, 4, and 5). Further increasing pH to 14, results in the replacement of both acac anions with four ammonia molecules (e.g., complex 3 and 6). The complexes 4 and 5 are pseudopolymorphs or solvates that are recovered from the same reaction mixture showing different morphology. These results are confirmed by NMR spectroscopy and single crystal X-ray diffraction. The crystallographic results have been amply supplemented by Hirshfeld surface analysis and other spectroscopic studies. The structural changes in complexes can impact the electronic properties and behavior of Pd(acac)2 in different chemical reactions. Therefore, it is important to consider the pH conditions when studying the structure and reactivity of Pd(acac)2 in various applications.

Regulation of Sensitized Phosphorescence in Two-Dimensional Lead Bromine Perovskites by Tuning Excited-State Interactions.

Excited-state interactions within the organic layer play a critical role in sensitized phosphorescence of two-dimensional (2D) perovskites. Herein, we regulate excited-state interactions utilizing isomeric organic ligands 1-naphthylmethylamine (1-NMA) and 1-(2-naphthyl)-methanamine (2-NMA). Transient absorption and first-principles calculations are employed to elucidate the mechanisms of triplet energy transfer (TET) and triplet excimer formation. The results indicate that wave function hybridization and tunneling effect at the inorganic/organic interface contribute to rapid (∼20 ps) and highly efficient (>98%) TET, with the triplet excimer being generated in (1-NMA)2PbBr4 at picosecond time-scale. However, triplet excimer is barely observed in (2-NMA)2PbBr4 due to varying ligand stacking modes. Despite rapid TET, the efficiency of sensitized phosphorescence is low (<0.5%), which is ascribed to pronounced nonradiative decay. By mixing isomeric ligands and optimizing respective ratio, a maximum phosphorescence enhancement of 7.6 folds is achieved. This work provides a detailed mechanistic understanding of triplet excimer sensitization and regulation of sensitized phosphorescence.

Orientational Compatibility Modulation of Ligands in Low-Symmetry Multi-Cavity Discrete Coordination Cages by Neighbouring Cage Participation.

Complexation of Pd(II) with a designer unsymmetrical bis-monodentate ligand (2:4 ratio) yielded a specific Pd2L4 type "single-cavity discrete coordination cage" (SCDCC), from a pool of 4 isomeric structures. The observed selctivity is attributed to inherent orientational preference of the ligand strands around the metal centers. Crafting a short coordinating arm at either ends of the bis-monodentate ligand (i.e the longer-arm) produced a pair of unsymmetrical isomeric tris-monodentate ligands; whereas crafting the same short-arm at both ends of the ligand gives an unsymmetrical tetrakis-monodentate ligand. Complexation of Pd(II) with either of the isomeric tris-monodenate ligands (3:4 ratio) resulted in corresponding low-symmetry "multi-cavity discrete coordination cage" MCDCC having two conjoined cavities, though the inherent relative orientational preference of the longer arms is not achievable in these cages. The enforced orientation is sustained by "Neighbouring Cage Participation" (NCP). However, one-pot combination of Pd(II), with a mixture of isomeric tris-monodenate ligands in 3:2:2 ratio produced an integratively self-sorted mixed-ligated MCDCC from a pool of 31 structures. Also, mixing Pd(II) with the tetrakis-monodentate ligand produced a MCDCC having three conjoined cavities. The inherent orientational preference of longer-arm of the ligand strands is retained in the mixed-ligated double-cavity and the homo-ligated triple cavity cages.

Isomeric organic ligands directing octamolybdates-linked Copper(II) functionalized complexes as active catalysts in electrochemistry and desulfurization

Two remarkable octamolybdates-based copper-organic complexes, namely, [Cu7(L)4(H2O)7(β-H2Mo8O26)]·7H2O (POM 1) and [Cu6(HX)4(β-Mo8O26)(H2O)6]·3H2O (POM 2) (H3L = 2-(pyridine-4-yl)-1H-imidazole-4,5-dicarboxylic acid; H3X = 2-(pyridine-3-yl)-1H-imidazole-4,5-dicarboxylic acid), were successfully assembled using two isomeric organic ligands under hydrothermal conditions. The two-dimensional metal-organic layers of POMs 1 and 2 were converted into three-dimensional frameworks by hexadentate β-H2Mo8O262− and tetradentate β-Mo8O264− clusters, respectively. The electrocatalytic properties of POM 1 were investigated, revealing its ability to catalyze the reduction of BrO3−, NO2− and H2O2 and the oxidation of ascorbic acid. Notably, POMs 1 and 2 demonstrated exceptional stability in organic solvents and exhibited excellent catalytic performance in oxidative desulfurization. When employed as catalysts for thioanisole oxidation, the conversion rates reached 94.5% after 150 min for POMs 1 and 99.9% after 120 min for POMs 2. In addition, their catalytic performances in model oil remained largely unchanged after five recycling cycles.

Gold(III) complexes with chloride and cyanopyridines: Facilitated hydrolysis of nitrile ligand to amide and antibacterial activity

A range of novel simple gold(III) compounds has been synthesized in their monocrystalline form, including two previously unknown chloro-complexes of Au3+ with 2-cyanopyridine or 3-cyanopyridine, respectively. Our investigations have revealed the intricate nature of the reaction between 2-cyanopyridine and tetrachloroauric acid, yielding at least three distinct products. The main product, obtained in high yield, is a salt featuring a tetrachloroauric anion and a pyridinium cation stabilized by a hydrogen bond to a further 2-cyanopyridine molecule. Moreover, we observed the in-situ formation of a 2-cyanopyridine-AuCl3 complex, which undergoes hydrolysis of the nitrile bond to yield a picolinamide-Au(III) complex. The complexes were characterized by IR and Raman spectroscopies, NMR spectroscopy, and single-crystal XRD studies. Additional computational studies were conducted to explain unusual spectral features, the observed disparities in the complexation reactions of the three isomeric cyanopyridine ligands and the distinct reactivity of the complex with 2-cyanopyridine. Based on these studies, we propose a mechanism for the catalyzed hydrolysis of the nitrile bond within the Au(III) complex. Finally, we assessed the antimicrobial efficacy of the synthesized gold(III) complexes against a spectrum of bacteria and fungi.

A Reduced-Symmetry Pd2L4 Cage from a Heterotopic Dipyridyl Ligand.

Two dipyridyl ligands, L3,3 and L3,4, have been used in combination with palladium(II) in the construction of metallosupramolecular species that show anion-dependent behavior in solution. A rare example of a low-symmetry (C2h) lantern-type cage is formed in one instance, [Pd2(L3,3)4]4+, while the isomeric ligand yields a larger double-walled square complex, [Pd4(L3,4)8]8+. [Pd2(L3,3)4](NO3)4 was isolated in crystalline form revealing two anions within the interior of the C2h-symmetry cage. The cage itself is held together by hydrogen bonding between "head-to-tail" pairs of ligands that reinforces the symmetry generated by the ditopic ligands. In solution, the cage with NO3- has sharp 1H nuclear magnetic resonance (NMR) signals at room temperature, while the BF4- analogue has broad signals that sharpen at higher temperatures or upon addition of (Bu4N)(NO3), highlighting the importance of the anion in templating or otherwise influencing self-assembly in solution. Altering the substitution position of one of the pyridyl rings yields a more "open" complex, with [Pd4(L3,4)8](NO3)8 being isolated as a crystalline solid. The double-walled square complex has a greater Pd···Pd separation due to the increased angle that the pyridyl groups subtend at the core of the ligand. NMR spectroscopy and mass spectrometry studies suggest a single species in the presence of nitrate but multiple species with tetrafluoroborate.

Preparation and study of a capillary electrochromatographic column prepared by conjugating β-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing β-cyclodextrin covalent organic frameworks (β-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26%RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

Ligand Isomerization Driven Electrocatalytic Switching.

The prevailing view about molecular catalysts is that the central metal ion is responsible for the reaction mechanism and selectivity, whereas the ligands mainly affect the reaction kinetics. Here, we question this paradigm and show that ligands have a dramatic influence on the selectivity of the product. We show how even a seemingly small change in ligand isomerization sharply alters the selectivity of the well-researched oxygen reduction reaction (ORR) Co phthalocyanine catalyst from an indirect 2e- to a direct 4e- pathway. Detailed analysis reveals that intramolecular hydrogen-bond interactions in the ligand activate the catalytic Co, directing the oxygen binding and thus deciding the final product. The resulting catalyst is the first example of a Co-based molecular catalyst catalyzing a direct 4e- ORR via ligand isomerization, for which it shows an activity close to the benchmark Pt in an actual H2-O2 fuel cell. The effect of the ligand isomerism is demonstrated with different central metal ions, thus highlighting the generalizability of the findings and their potential to open new possibilities in the design of molecular catalysts.

Ligand Isomerization Driven Electrocatalytic Switching

AbstractThe prevailing view about molecular catalysts is that the central metal ion is responsible for the reaction mechanism and selectivity, whereas the ligands mainly affect the reaction kinetics. Here, we question this paradigm and show that ligands have a dramatic influence on the selectivity of the product. We show how even a seemingly small change in ligand isomerization sharply alters the selectivity of the well‐researched oxygen reduction reaction (ORR) Co phthalocyanine catalyst from an indirect 2e− to a direct 4e− pathway. Detailed analysis reveals that intramolecular hydrogen‐bond interactions in the ligand activate the catalytic Co, directing the oxygen binding and thus deciding the final product. The resulting catalyst is the first example of a Co‐based molecular catalyst catalyzing a direct 4e− ORR via ligand isomerization, for which it shows an activity close to the benchmark Pt in an actual H2−O2 fuel cell. The effect of the ligand isomerism is demonstrated with different central metal ions, thus highlighting the generalizability of the findings and their potential to open new possibilities in the design of molecular catalysts.

Stable CAAC-Triazenes: A New Nitrogen Ligand System With Donor and Conformational Flexibility, and With Application in Olefin Activation Catalysis.

N-heterocyclic imines such as pyridylidene amines impart high catalytic activity when coordinated to a transition metal, largely imposed by their electronic flexibility. Here, this donor flexibility has been applied for the first time to CAAC-based systems through the synthesis of CAAC-triazenes. These new ligands offer a larger π-conjugation that extends from the N-heterocyclic carbene through three nitrogens rather than just one, as observed in N-heterocyclic imines. We demonstrate the straightforward synthesis of three new CAAC-triazenes containing different substituents on the terminal triazene nitrogen. These compounds are remarkably stable up to 120 °C without loss of N2 as typically observed with similar triazenes. E-to-Z isomerization within the triazene is instigated by UV light and is partially reversible dependent on the triazene substituent. The quinoline-substituted CAAC-triazene 1-Q has been applied as an L,L'-type ligand in the synthesis of [PdCl2(1-Q)], [PdCl(Me)(1-Q)] and [Pd(Me)(H2O(1-Q)]+. E-to-Z ligand isomerization also occurs when coordinated to PdCl2, providing access to on-metal manipulation. The cationic complex [PdMe(H2O)(1-Q)]+ is a precatalyst for oligomerization of ethylene to form initially 2-butene and subsequently linear and branched C8-C12 products from butene activation. Moreover, isomerization of 1-hexene takes place efficiently with exceptionally low catalyst loading (10 ppm) and up to 74,000 turnover numbers.

Synthesis, Characterization, and Reactivity of Bispidine-Iron(IV)-Tosylimido Species.

Reported are the synthesis and detailed studies of the iron(IV)-tosylimido complexes of two isomeric pentadentate bispidine ligands (bispidines are 3,7-diazabicyclo[3.3.1]nonane derivatives). This completes a series of five tosylimido complexes with comparable pentadentate amine/pyridine ligands, where the corresponding [(L)FeIV═O]2+ oxidants have been studied in detail. The characterization of the two new complexes in solution (UV-vis-NIR, Mössbauer, HR-ESI-MS) shows that these oxidants have an intermediate spin (S = 1) electronic ground state. The reactivities have been studied as oxidants in C-H activation at 1,3-cyclohexadiene and nitrogen atom transfer to thioanisole. For the latter substrate, the entire set of data for the five ligands and for both nitrogen and oxygen atom transfer is now available and the interesting observation is that oxygen atom transfer is, as expected, generally faster than nitrogen atom transfer, with the exception of the two ligands that have four and three pyridine groups oriented parallel to the Fe-O and Fe-N axes. A thorough DFT analysis indicates that this is due to steric effects in the case of the [(L)FeIV═O]2+ species, which are less important in the [(L)FeIV═NTs]2+ compounds due to partial electron transfer from the thioanisole substrate to the iron(IV)-tosylimido oxidant.

Topological investigation on the structural diversity of Co(II) coordination polymers with mixed ligands: Effect of ligand isomerism and substituent

Co(II) coordination polymers constructed from the isomeric N,N’-bis(3-pyridylmethyl)oxalamide (L1) and N,N’-bis(4-pyridylmethyl)oxalamide (L2) and polycarboxylic acids with different substituents at the 5th positions of the phenyl rings are reported, including {[Co(L1)(1,3,5-HBTC)]·H2O}n (1,3,5-H3BTC = benzene-1,3,5-tricarboxylic acid), 1, {[Co(L1)(5‑tert-IPA)(H2O)2]·H2O}n (5‑tert-H2IPA = 5‑tert-butylbenzene-1,3-dicarboxylic acid), 2, [Co(L1)0.5(5-NH2-IPA)(H2O)]n (5-NH2H2IPA = 5-aminoisophthalic acid), 3, {[Co2(L2)2(1,3,5-HBTC)2]·(L2)·5H2O}n, 4, {[Co(L2)1.5(1,3,5-HBTC)]·2H2O}n, 5, {[Co(L2)(5‑tert-IPA)]·H2O}n, 6, {[Co(L2)(5-NH2-IPA)(H2O)]·2·5H2O}n, 7, {[Co(L2)(5-NH2-IPA)]·4H2O}n, 8. Complexes 1, 3, 5 and 6 are 2D nets with the 3,5L2, bey, bey, 3,5L2 topologies, and 2 is a 3-fold interpenetrated 2D net with the hcb topology, whereas 4 is a 3D framework with the pcu topology, 7 is a self-catenated 3D net with the 3,5T48 topology and 8 is a 3-fold interpenetrated 3D net with the 3,5T1 topology, respectively. While the solvent system and energy are important in the preparation of Co(II) coordination polymers, the ligand isomerism of the neutral spacer ligand and the identity of the substituent group of the polycarboxylate ligand govern the structural diversity.

Fine tuning dynamic magnetism of dysprosiacarboranyl sandwiches

A series of isomeric sandwich-type dysprosiacarboranyl complexes, including [Na(THF)5][3,2'-(THF)2-3,2'-Dy(1,2-C2B9H11)x(1',7'-C2B9H11)2–x] (o/m-Dy) and [Na(THF)5][2,2'-(THF)2-2,2'-Dy(1,7-C2B9H11)2] (m-Dy) were synthesized by using the isomeric dicarbollide ligands, namely [nido-7,8-C2B9H11]2– and [nido-7,9-C2B9H11]2−. The structural details of o/m-Dy and m-Dy and magnetic dynamics of m-Dy were investigated to compare with the previous study on [Na(THF)5][2,2'-(THF)2-2,2'-Dy(1,2-C2B9H11)2] o-Dy. The bending angles of sandwiched dysprosiacarboranes are straightened so as to improve energy barriers (Ueff) from 430(5) to 591(0) K. Magneto-structural correlations show that the introduction of meta-C sites within the π-electron delocalized heterocyclic ring can effectively shorten the Dy–C2B3 centroid distance and increase the C2B3centroid∙∙∙Dy∙∙∙C2B3centroid bending angle, which is attributed to the differences in electronegativity between C and B atoms on the ring of C2B32–. Therefore, to further enhance the performance of single-molecule magnets (SMMs) on this basis, future endeavors should focus on diminishing the equatorial solvent molecules to make a wider C2B3∙∙∙Dy∙∙∙C2B3 bending angle.

Organodiphosphines in cis-Pt(η2-PX n P)(Cl)2 (n = 1,2,3) derivatives: Structural aspects

Abstract This article covers almost 130 Pt(ii) complexes with an inner coordination sphere of cis-PtP2Cl2. The P-donor ligands are organodiphosphines that create four-, five-, and six-membered metallocyclic rings. There are two types of four-membered rings: PCP and PNCP, and four types of five-membered rings: PC–CP, PC═CP, PNNP, and PCOP. There are wide varieties of the six-membered metallocyclic rings: PC3P (most common), PCNCP, PCSCP, PCSiCP, PNCNP, PCCOP, PCCNP, POPNP, POSiOP, P(CNC)2P, and P(CNC)(CCC)P. The P–Pt–P bite angles open with the size of the metallocyclic rings in the order (total mean values 72.4° [PXP] &lt; 86.4° [PXXP] &lt; 94.0° [PXXNP]). There are complexes that are examples of distortion and ligand isomerism. The structural data are analyzed and discussed.

Polymorphism and Structural Variety in Sn(II) Carboxylate Coordination Polymers Revealed from Structure Solution of Microcrystals.

The crystal structures of four coordination polymers constructed from Sn(II) and polydentate carboxylate ligands are reported. All are prepared under hydrothermal conditions in KOH or LiOH solutions (either water or methanol-water) at 130-180°C and crystallize as small crystals, microns or less in size. Single-crystal structure solution and refinement are performed using synchrotron X-ray diffraction for two materials and using 3D electron diffraction (3DED) for the others. Sn2 (1,3,5-BTC)(OH), where 1,3,5-BTC is benzene-1,3,5-tricarboxylate, is a new polymorph of this composition and has a three-dimensionally connected structure with potential for porosity. Sn(H-1,3,5-BTC) retains a partially protonated ligand and has a 1D chain structure bound by hydrogen bonding via ─COOH groups. Sn(H-1,2,4-BTC) contains an isomeric ligand, benzene-1,2,4-tricarboxylate, and contains inorganic chains in a layered structure held by hydrogen bonding. Sn2 (DOBDC), where DOBDC is 2,5-dioxido-benzene-1,4-dicarboxylate, is a new polymorph for this composition and has a three-dimensionally connected structure where both carboxylate and oxido groups bind to the tin centers to create a dense network with dimers of tin. In all materials, the Sn centers are found in highly asymmetric coordination, as expected for Sn(II). For all materials phase purity of the bulk is confirmed using powder X-ray diffraction, thermogravimetric analysis, and infrared spectroscopy.

N^N^C-Cyclometalated rhodium(III) complexes with isomeric pyrimidine-based ligands: unveiling the impact of isomerism on structural motifs, luminescence and cytotoxicity.

The impact of isomerism of pyrimidine-based ligands and their rhodium(III) complexes with regard to their structures and properties was investigated. Two isomeric ligands, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL2,5) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL2,5 is more distorted due to presence of pyrazolyl and phenyl groups in the neighbouring positions 4 and 5 of the pyrimidine ring. The complexation of HL2,5 and HL2,6 with RhCl3 leads to the sp2 C-H bond activation, resulting in the isolation of two complexes, [RhL2,5(Solv)Cl2]·nEtOH and [RhL2,6(Solv)Cl2]·nEtOH (Solv = H2O, EtOH), with the deprotonated forms of the pyrazolylpyrimidine molecules which coordinate the Rh3+ ion as N^N^C-tridentate ligands. According to DFT modelling, the mechanism of the deprotonation involves (i) the C-H bond breaking in the 2-phenyl group followed by the coordination of the C atom to the Rh atom, (ii) the protonation of coordinated chlorido ligand, (iii) the ejection of the HCl molecule and (iv) the coordination of the H2O molecule. The ligand isomerism has an impact on emission properties and cytotoxicity of the complexes. Although the excited states of the complexes effectively deactivate through S0/T1 and S0/S1 crossings associated with the cleavage of the weak H2O ligands upon excitation, the [RhL2,5(Solv)Cl2]·nEtOH complex appeared to be emissive in the solid state, while [RhL2,6(Solv)Cl2]·nEtOH is non-emissive at all. The complexes show significant cytotoxic activity against cancerous HepG2 and Hep2 cell lines, with the [RhL2,6(Solv)Cl2]·nEtOH complex being more active than its isomer [RhL2,5(Solv)Cl2]·nEtOH. On the other hand, noticeable cytotoxicity of the latter against HepG2 is supplemented by its non-toxicity against non-cancerous MRC-5 cells.

Trifluoromethyl-pyridine carboxylic acid Zn(ii) complexes: isomeric effects on coordination and biological activity

Due to the isomerization effect of ligands, the coordination patterns of two Zn(ii) complexes and the binding activity with BSA and CT-DNA are changed. Chelate effect increases the binding properties of the complexes with biological macromolecules.

Fuel from waste: electrosynthesizing ammonia directly from agricultural digestate through ligand isomerization

Ligand isomerization driven ammonia electrosynthesis from agricultural waste water.

Theoretical Studies of Xanthates in Heavy Metal Complexation: Understanding the Structural, Thermochemical, and Electronic Aspects

Heavy metals have been widely discussed as a significant cause of environmental disasters in recent decades. One of the main focuses has been exploring agents and mechanisms capable of removing these metals from nature. Under this perspective, xanthates have been studied as sequestering agents of these metals in aqueous environments. In this theoretical study, complexes of cadmium(II) and mercury(II), with different coordination modes and geometric isomers of the xanthate ligands (n-propyl, n-butyl, and n-pentyl xanthates), were evaluated using density functional theory. To verify the versatility of coordination modes of the xanthates, monodentate and bidentate structures were optimized. For these compounds, structural, thermochemical, and electronic parameters were studied. The thermochemical results showed that all complexes are formed through exothermic and spontaneous processes. Electronic analysis showed that the mercury(II) complexes have a higher covalent character of the Hg-S bond, in contrast with the cadmium(II) complexes, which exhibited a higher ionic character of the Cd-S bond. Through the analysis of the natural bond orbitals, the Lewis acid-base nature of these complexes was confirmed and corroborated by the softness calculations, with the participation of the p orbitals of the sulfur and s orbitals of the metal centers.

Are the metal identity and stoichiometry of metal complexes important for colchicine site binding and inhibition of tubulin polymerization?

Quite recently we discovered that copper(II) complexes with isomeric morpholine-thiosemicarbazone hybrid ligands show good cytotoxicity in cancer cells and that the molecular target responsible for this activity might be tubulin. In order to obtain better lead drug candidates, we opted to exploit the power of coordination chemistry to (i) assemble structures with globular shape to better fit the colchicine pocket and (ii) vary the metal ion. We report the synthesis and full characterization of bis-ligand cobalt(III) and iron(III) complexes with 6-morpholinomethyl-2-formylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL1), 6-morpholinomethyl-2-acetylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL2), and 6-morpholinomethyl-2-formylpyridine 4N-phenyl-3-thiosemicarbazone (HL3), and mono-ligand nickel(II), zinc(II) and palladium(II) complexes with HL1, namely [CoIII(HL1)(L1)](NO3)2 (1), [CoIII(HL2)(L2)](NO3)2 (2), [CoIII(HL3)(L3)](NO3)2 (3), [FeIII(L2)2]NO3 (4), [FeIII(HL3)(L3)](NO3)2 (5), [NiII(L1)]Cl (6), [Zn(L1)Cl] (7) and [PdII(HL1)Cl]Cl (8). We discuss the effect of the metal identity and metal complex stoichiometry on in vitro cytotoxicity and antitubulin activity. The high antiproliferative activity of complex 4 correlated well with inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity were supported by experimental results and molecular docking calculations.