Browsing by Author "Omondi, Reinner O."

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    Biomolecular interactions of 1,3-bis(2-arylimino)isoindolate-based palladium(II) complexes: Substitution kinetics, DNA/protein-binding, and molecular docking approaches
    (Inorganica Chimica Acta, 2023-12-01) Onunga, Daniel O.; Omondi, Reinner O.; Sitati, Meshack; Mutua, Gershom K.; Jaganyi, Deogratius; Mambanda, Allen
    A series of 1,3-bis(2-arylimino)isoindoline Pd(II) complexes core viz.; Chlorido(1,3-bis(2-pyridylimino)isoindoline)palladium(II), Pd1, Chlorido(1,3-bis(4-methyl-2-pyridylimino)isoindoline)palladium(II), Pd2, Chlorido(1,3-bis(2-pyridylimino)benz(f)isoindoline)palladium(II), Pd3 and Chlorido(1,3-Bis(1-isoquinolylimino)isoindoline)palladium(II), Pd4 were synthesized, appropriately characterized and the crystal structure of Pd2 elucidated. The kinetics and mechanism of the substitution of the chloride ligand with thiourea ligands, Tu, Dmtu and Tmtu, from the complexes were investigated under pseudo-first-order conditions. The analyses were performed using stopped-flow analyzer or UV–visible spectrophotometer. The reactions proceeded through two consecutive steps for most complexes with exception of Pd4 showing only a single step. The substitution rates followed the order: Pd1>Pd2>Pd3>Pd4 due to varying degrees of steric influences and σ-/π-donations caused by the methylation and benzannulation on the cis-/trans-positions of the pyridyl rings of the BPI. The quenching of the fluorescence of CT-DNA/EB by the Pd(II) complexes suggests static quenching mechanism. The simulated docking of the complexes onto CT-DNA suggests they bind mainly in the minor grooves of DNA. The UV–Visible absorption titrations and quenching of tryptophan (Trp) fluorescence of BSA by the complexes depict reasonable interactions which occur mainly in the hydrophobic domains of the former. The order of strength of the interaction of the complexes with DNA or BSA is consistent with the rates of substitution kinetics.
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    Electronic and ring size effects of N-heterocyclic carbenes on the kinetics of ligand substitution reactions and DNA/protein interactions of their palladium(II) complexes
    (Springer link, 2023-05-15) Ojwach, Stephen O.; Jaganyi, Deogratius; Omondi, Reinner O.
    The synthesis, substitution kinetics and DNA/BSA interactions of four cationic Pd(II) complexes [Pd(1)Cl]BF4 (Pd1), [Pd(2)Cl]BF4 (Pd2), [Pd(3)Cl]BF4 (Pd3) and [Pd(4)Cl]BF4 (Pd4), derived from the reaction of [PdCl2(NCCH3)2] with ligands 2,6-bis(3-methylimidazolium-1-yl)pyridine dibromide (1), 2,6-bis(3-ethylimidazolium-1-yl)pyridine dibromide (2), 2,6-bis(1-methylimidazole-2-thione)pyridine (3), and 2,6-bis(1-ethylimidazole-2-thione)pyridine (4), respectively are reported. The complexes were characterised by various spectroscopic techniques and single crystal X-ray diffraction for compound Pd2. Kinetic reactivity of the complexes with the biologically relevant nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5′-monophosphate sodium salt (5’-GMP) was in the order: Pd1 > Pd2 > Pd3 > Pd4, which was largely dependent on the electronic and ring size of the chelate ligands, consistent with Density functional theory (DFT) simulations. The interactions of the complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) binding titrations showed strong binding. Both the experimental and in silico data reveal CT-DNA intercalative binding mode. Graphical abstract Similar content being viewed by others Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity Article 15 July 2021 Guanidine- and purine-functionalized ligands of FeIIIZnII complexes: effects on the hydrolysis of DNA Article 02 July 2019 COORDINATION OF AN AMINO ALCOHOLIC SCHIFF BASE LIGAND TOWARD THE ZINC(II) ION: SPECTRAL, STRUCTURAL, THEORETICAL, AND DOCKING STUDIES Article 01 December 2021
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    Palladium(II) complexes of tridentate bis(benzazole) ligands: Structural, substitution kinetics, DNA interactions and cytotoxicity studies
    (Journal of Inorganic Biochemistry, 2020-09-01) Omondi, Reinner O.; Bellam, Rajesh.; Ojwach, Stephen O.; Jaganyi, Deogratius.; Fatokun, Amos A.
    Reactions of 2,6-bis(benzimidazol-2-yl)pyridine (L1), 2,6-bis(benzoxazol-2-yl)pyridine (L2), and 2,6-bis(benzothiazol-2-yl)pyridine (L3) with [Pd(NCMe)2Cl2] in the presence of NaBF4 afforded the corresponding Pd(II) complexes, [Pd(L1)Cl]BF4, PdL1; [Pd(L2)Cl]BF4, PdL2; [Pd(L3)Cl]BF4, PdL3; respectively, while reaction of bis[(1H-benzimidazol-2-yl)methyl]amine (L4) with [Pd(NCMe)2Cl2] afforded complex [Pd(L4)Cl]Cl, PdL4. Characterisation of the complexes was accomplished using NMR, IR, MS, elemental analyses and single crystal X-ray crystallography. Ligand substitution kinetics of these complexes by biological nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5-GMP) were examined under pseudo-first order conditions. The reactivity of the complexes decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, ascribed to electronic effects. Density functional theory (DFT) supported this trend. Studies of interaction of the Pd(II) complexes with calf thymus DNA (CT-DNA) revealed strong binding affinities via intercalative binding mode. Molecular docking studies established associative non-covalent interactions between the Pd complexes and DNA. The in vitro cytotoxic activities of PdL1–PdL4 were assessed in cancer cell lines HeLa and MRC5-SV2 and a normal cell line MRC-5, using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. PdL1 exhibited cytotoxic potency and selectivity against HeLa cell that was comparable to cisplatin's. Complex PdL1, unlike cisplatin, did not significantly induce caspase-dependent apoptosis.
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    (Pyrazolyl)pyridine ruthenium(III) complexes: Synthesis, kinetics of substitution reactions with thiourea and biological studies
    (Inorganic Chemistry Communications, 2024-08-01) Omondi, Reinner O.; Ojwach, Stephen O.; Jaganyi, Deogratius.; Fatokun, Amos A.
    Reactions of 2-bromo-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (L1), 2,6-di (1H-pyrazol-1-yl) pyridine (L2) and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (L3) with RuCl3·3H2O led to the formation of their respective metal complexes [RuCl3(L1)] (1), [RuCl3(L2)] (2) and [RuCl3(L3)] (3). Solid state structure of complex 3 established the formation of a six-coordinate mononuclear compound in which L3 is tridentately bound. The order of reactivity of the studied complexes with thiourea (TU) nucleophile is in the form 1 > 2 > 3, in line with density functional theory (DFT) studies. The complexes displayed minimal cytotoxic activity against the HeLa cell line, consistent with molecular docking experiments which showed weaker DNA binding affinities.
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    Review of comparative studies of cytotoxic activities of Pt(II), Pd(II), Ru(II)/(III) and Au(III) complexes, their kinetics of ligand substitution reactions and DNA/BSA interactions
    (Inorganica Chimica Acta, 2020-11-01) Omondi, Reinner O.; Ojwach, Stephen O.; Jaganyi, Deogratius.
    New concepts and various strategies are being explored to improve the cytotoxicity of metal-based complexes. One of those strategies is to fine-tune the substitution kinetics of metallo-drugs to limit competive substitution, and hence maximise delivery to the cellular targets, DNA or proteins. To date, it appears there is a missing link in understanding the correlation between kinetics of ligand substitution reactions, biomolecule interactions and their respective cytotoxicity. While there are a number of orginal and review articles reporting the kinetics of ligand substitution reaactions, DNA/BSA interactions and cytotoxicity of metal compelxes, independently, very few papers report these three studies simultaneously. In fact, there is no single review that has attempted to capture the link between kinetics of ligand subsititution reactions and biomolecule interactions on cytotoxicity of metal complexes. In this current review, we examine the correlations between the kinetics of ligand substitution reactions and DNA interactions, protein binding (BSA) and cytotoxicity activities of some Pt(II)/(IV), Pd(II), Ru(II)/Ru(III) and Au(III) metallo-based drugs reported in literature. While limited data is available, it is envisaged that this review shall in part motivate and stimulate more comparative studies.
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    Role of π-conjugation on the coordination behaviour, substitution kinetics, DNA/BSA interactions, and in vitro cytotoxicity of carboxamide palladium(ii) complexes
    (Royal society of chemistry, 2021-05-24) Omondi, Reinner O.; Ojwach, Stephen O.; Sibuyi , Nicole Remaliah Samantha; Adewale, Fadaka; Meyer, Mervin Oluwaseun; Jaganyi, Deogratius
    Treatments of N-(pyridin-2-ylmethyl)pyrazine-2-carboxamide (L1), N-(quinolin-8-yl)pyrazine-2-carboxamide (L2), N-(quinolin-8-yl)picolinamide (L3) and N-(quinolin-8-yl)quinoline-2-carboxamide (L4) with [PdCl2(NCMe)]2 afforded the corresponding Pd(II) complexes, [Pd(L1)Cl] (PdL1); [Pd(L2)Cl] (PdL2); [Pd(L3)Cl] (PdL3); and [Pd(L4)Cl] (PdL4) in moderate yields. Structural characterisation of the compounds was achieved by NMR and FT-IR spectroscopies, elemental analyses and single crystal X-ray crystallography. The solid-state structures of complexes PdL2–PdL4 established the presence of one tridentate carboxamide and Cl ligands around the Pd(II) coordination sphere, to give distorted square planar complexes. Electrochemical investigations of PdL1–PdL4 showed irreversible one-electron oxidation reactions. Kinetics reactivity of the complexes towards bio-molecules, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5′-GMP) decreased in the order: PdL1 > PdL2 > PdL3 > PdL4, in tandem with the density functional theory (DFT) data. The complexes bind favourably to calf thymus (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions agrees with the substitution kinetics trends. The in vitro cytotoxic activities of PdL1–PdL4 were examined in cancer cell lines A549, PC-3, HT-29, Caco-2, and HeLa, and a normal cell line, KMST-6. Overall, PdL1 and PdL3 displayed potent cytotoxic effects on A549, PC-3 HT-29 and Caco-2 comparable to cisplatin. All the investigated complexes exhibited lower toxicity on normal cells than cisplatin.
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    Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes
    (Springer link, 2022-10-05) Omondi, Reinner O.; Fadaka,Adewale O.; Fatokun, Amos A.; Jaganyi, Deogratius; Ojwach, Stephen
    The pincer complexes, [Pd(L1)Cl]BF4 (PdL1), [Pd(L2)Cl]BF4 (PdL2), [Pd(L3)Cl]BF4 (PdL3), [Pd(L4)Cl]BF4 (PdL4) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L1), bis[2-(1H-pyrazol-1-yl)ethyl]amine (L2), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L3), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L4) with [PdCl2(NCMe)]2 in the presence NaBF4. The solid‐state structures of complexes PdL1–PdL4 confirmed a tridentate coordination mode, with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5’-GMP) followed the order: PdL2 < PdL3 < PdL4, and PdL2 < PdL1. The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL1–PdL4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC50 > 100 µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).
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    Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes
    (JBIC Journal of Biological Inorganic Chemistry, 2022-10-05) Omondi, Reinner O.; Fadaka, Adewale O.; Fatokun, Amos A.; Jaganyi, Deogratius.; Ojwach, Stephen O.
    The pincer complexes, [Pd(L1)Cl]BF4 (PdL1), [Pd(L2)Cl]BF4 (PdL2), [Pd(L3)Cl]BF4 (PdL3), [Pd(L4)Cl]BF4 (PdL4) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L1), bis[2-(1H-pyrazol-1-yl)ethyl]amine (L2), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L3), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L4) with [PdCl2(NCMe)]2 in the presence NaBF4. The solid‐state structures of complexes PdL1–PdL4 confirmed a tridentate coordination mode, with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5’-GMP) followed the order: PdL2 < PdL3 < PdL4, and PdL2 < PdL1. The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL1–PdL4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC50 > 100 µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).