Browsing by Author "Richardson, Christopher"

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    Crystal structures, in vitro and in silico biological studies of copper mefenamato complexes with aliphatic diamines
    (Elsevier, 2025) Vernekar, Beena K.; Sawant, Pradnya S.; Breckell, Jaxon; Kotkar, Gayatri; D’souza, Luann R.; Butcher, Raymond J.; Richardson, Christopher
    Two new copper complexes with the nonsteroidal anti-inflammatory drug mefenamic acid (Hmef) and 1,2-propanediamine (1,2-pn), and 1,3-propanediamine (1,3-pn) were synthesised and characterised by spectroscopic techniques and thermal analysis. The crystal structures of [Cu(1,2-pn)2(H2O)2].(mef)2,{bis(aqua)bis(1,2-propanediamine)copper(II) mefenamate} MEF1, and [Cu(mef)2(1,3-pn)2] {bis(1,3-propanediamine)bis(mefenamato)copper(II)} MEF2, were determined by single crystal X-ray crystallography. The structure determinations showed MEF1 is a mefenamate salt, and MEF2 binds mefenamate in a bidentate chelating manner. The XPS studies revealed the identity of copper in the +2 oxidation state for both MEF1 and MEF2. Moreover, the ligand functionality in the compounds was also evidenced from the binding energy values corresponding to C1s, O1s, and N1s levels. The solid-state EPR spectra of MEF1 and MEF2 at 77 K presents two different g values demonstrating g‖ >g⊥> 2.0023 (ge) consistent with a normal axial spectrum revealing an elongated octahedral geometry for Cu(II) i.e. t2g6 and eg3 (dz2)2, (dx2-y2)1 with the unpaired electron residing in the dx2-y2 orbital for MEF1 and a compressed octahedron for MEF2 with the unpaired electron residing in the dz2 orbital. The mefenamato complexes displayed promising cytotoxic potential against MCF-7 human breast cancer cell lines. Interactions of the complexes with the binding site of tyrosinase receptor (2y9x) and DNA intercalation studies were evaluated using molecular docking, providing a deeper structural understanding of the efficacies of these metallodrugs. The comparison between theoretical calculations of tyrosinase receptor with the tyrosinase enzyme depicted comparable results to the standard kojic acid.
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    Ibuprofenato cobalt complexes: Structural insights, DNA interaction studies, and biological evaluation.
    (Elsevier, 2025) Vernekar, Beena K.; Breckell, Jaxon R.; Butcher, Raymond J.; Maliwal, Deepika; Pissurlenkar, Raghuvir R. S.; Gaonkar, Sanket K.; Barretto, Delicia A.; Sattarker, Saurav D.; Richardson, Christopher
    Two new cobalt complexes with the nonsteroidal anti-inflammatory drug Ibuprofen (IbuH) and N-donor co-ligands, 2,2-dipyridylamine (dipyam) and 1,10-phenanthroline (o-phen), were synthesised. The complexes were characterised by spectroscopic techniques and thermal analysis, and the crystal structures of [Co(Ibu)2(dipyam)]·H2O (IBU1) and [Co(Ibu)2(o-phen)(H2O)]·½H2O (IBU2) were determined by single-crystal X-ray crystallography. IBU2 exhibited better antibacterial activity, with Minimum Inhibitory Concentration (MIC) values ranging from 20 to 40 μM, compared to IBU1. The metal complexes also showed antioxidant activity with IC50 values of 39.71±0.86 and 37.43±0.91 μM for IBU1 and IBU2, respectively. We also found that IBU1 and IBU2 exhibited DNA binding and DNA cleavage efficacy. The ibuprofenato metal complexes showed promising anticancer activity against MCF-7 breast cancer cells with IC50 values of 88.5±0.06 μM and 111.1±0.02 μM for IBU1 and IBU2, respectively, compared to higher IC50 values against normal L929 cell lines. Interactions of the complexes with the binding site of the Estrogen Receptor alpha (ER-α) were evaluated using molecular docking and molecular dynamics simulations, providing a deeper structural understanding of the efficacies of these metallodrugs.
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    New diclofenac salts with the dense hydrogen bond donor propane-1,3-diaminium
    (Royal Society of Chemistry, 2024) Breckell, Jaxon R.; Conte, Luke; Potts, Michael W.; Sawant, Pradnya S.; Butcher, Raymond J.; Vernekar, Beena K.; Richardson, Christopher
    A series of solvatomorphic structures of the anti-inflammatory drug diclofenac (dcfn−) and the dense hydrogen bond donor propane-1,3-diaminium (H2pn2+) are reported. Single crystal X-ray diffraction shows each structure contains a dcfn2·H2pn formula unit (1) with solvent of crystallisation [1·2H2O, 1·3H2O, 1·2MeOH, 1·EtOH·2H2O, 1·iPrOH, 1·2DMSO]. The propane-1,3-diaminium molecules evoke extensive networks of hydrogen-bonded interactions with the solvates and the dcfn carboxylate groups. All structures are lamellar with hydrophilic solvate-containing sheets separating hydrophobic layers of aromatic dcfn moieties. Supporting characterisations by powder X-ray diffraction, Fourier transform infrared and 1H NMR spectroscopies, thermal analysis (TG–DSC) and elemental microanalysis were used to reveal the sometimes delicate phase distributions amongst this set of compounds. TG–DSC showed a consistent pattern across the water and alcohol-containing compounds with desolvation occurring before melting to an anhydrous ionic liquid form around 140–150 °C. Heating to approximately 200 °C induces a minor dehydration reaction that covalently links diclofenac and propan-1,3-diaminium molecules via amide bond formation. A mechanochemical synthetic route to 1·3H2O was determined and this compound was selected for study by gravimetric water vapour adsorption. These studies showed the lamellar structure of 1·3H2O displays reversible but imperfect water adsorption between 0% and 50% relative humidity, which is ascribed to some crystal fatigue. This work expands crystal engineering strategies for new and existing active pharmaceutical ingredients to low molecular weight diamines.