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A series of manganese complexes bearing 6-nitropiperonal thiosemicarbazone ligands have been synthesized and characterized. The ligands differ by the alkyl substituent on the amine nitrogen. These complexes, formulated as Mn(CO)3(TSC)Br, where TSC represents the thiosemicarbazone ligand, show very rapid release of carbon monoxide upon exposure to light, establishing them as photoCORMs (light activated carbon monoxide-releasing molecules). The photo-reactivity profile of the complexes have been studied in detail using the myoglobin assay as a detection system for carbon monoxide. Three different wavelengths of light were used: 365 nm (UV), 405 nm (purple) and 435 nm (blue). It was observed that the half-life for the CO release was dependent on the wavelength of light. These half-lives were on the order of 10 to 100 seconds which is very fast for this type of complex. Typically, the half-lives increased with a decrease in the energy of the incident radiation. For the compound bearing the phenyl-substituted amine group, t½ (in seconds) was 44.54, 59.59 and 65.90 for the UV, purple and blue light respectively. The amount of CO released was also wavelength dependent, with higher energy wavelength generally releasing more CO. UV light caused 2 equivalents of CO to be released while roughly 1.5 and 1.0 equivalents were released for the purple and blue light respectively. The biological profile of the complexes were also studied using antibacterial and anticancer assays. Against both Gram-negative and Gram-positive bacteria, the complexes showed good growth inhibitory effects with minimum inhibitory concentration (MIC) values no higher than 50 μM and as low as 3.13 μM. More importantly, these estimated MIC values were noticeably reduced when the bacteria, incubated with the complexes, were irradiated. All four compounds displayed intrinsic cytotoxicity against HEK293T (kidney) and A549 (lung carcinoma) cell lines, as indicated by relatively efficient cell killing for CORMs without irradiation. Irradiation of treated cultures with short wavelength visible spectrum light augmented these cytotoxic effects.

A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49–7.50) × 10 4 M − 1 . In relation to HSA, the complexes interact strongly with binding constants on the order of 10 5 M − 1 . The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals. The antimicrobial profiles of the compounds, tested against a panel of microbes including five of the ESKAPE pathogens ( Staphylococcus aureus , MRSA , Escherichia coli , Klebsiella pneumoniae , MDR , Acinetobacter baumannii , Pseudomonas aeruginosa ) and two yeasts ( Candida albicans and Cryptococcus neoformans var. grubii ), are also described. The compounds contain a core moiety that is similar to oxolinic acid, a quinolone antibiotic that targets DNA gyrase and topoisomerase (IV). The binding interaction between the complexes and these important antibacterial targets were studied by computational methods, chiefly docking studies. The calculated dissociation constants for the interaction with DNA gyrase B (from Staphylococcus aureus ) range from 4.32 to 24.65 μM; the binding was much stronger to topoisomerase IV, with dissociation constants ranging from 0.37 to 1.27 μM.

We have synthesized a trio of gallium complexes bearing 9-anthraldehyde thiosemicarbazones. The complexes were assessed for their anticancer activity and their biophysical reactivity was also investigated. The three complexes displayed good cytotoxic profiles against two human colon cancer cell lines, HCT-116 and Caco-2. The IC50 ranged from 4.7 – 44.1 μM with the complex having an unsubstituted amino group on the thiosemicarbazone being the most active. This particular complex also showed a high therapeutic index. All three complexes bind strongly to DNA via intercalation with binding constants ranging from 7.46 × 104 M-1 to 3.25 × 105 M-1. The strength of the binding cannot be directly related to the level of anticancer activity. The complexes also bind strongly to human serum albumin with binding constants on the order of 104 – 105 M-1 as well. The complexes act as chemical nucleases as evidenced by their ability to cleave pBR322 plasmid DNA. The binding constants along with the cleavage results may suggest that the extent of DNA interaction is not directly correlated with anticancer activity. The results of docking studies with DNA, ribonucleotide reductase and human serum albumin, however showed that the complex with the best biological activity had the largest binding constant to DNA.

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thiosemicarbazones (RHpTSC where R = H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R = CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 10 4 M − 1 . They are also strong binders of human serum albumin with binding constants near 10 4 M − 1 . The complexes show good in vitro cytotoxic profiles against two human colon cancer cell lines (HCT-116 and HT29) and two human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values in the low millimolar concentration range.

The synthesis and characterization of a number of organometallic ruthenium(II) complexes containing a series of bidentate thiosemicarbazone ligands derived from piperonal is reported. The structure of compounds have been confirmed by spectroscopic analysis (IR and NMR) as well as X-ray crystallographic analysis of [(η 6 - p -cymene)Ru(pPhTSC)Cl]Cl ( 4 ) (pPhTSC is piperonal-N(4)-phenylthiosemicarbazone). The interaction of the complexes ([(η 6 - p -cymene)Ru(pEtTSC)Cl]Cl) ( 3 ) (pEtTSC is piperonal-N(4)-ethylthiosemicarbazone) and 4 with calf thymus DNA, human serum albumin (HSA) and pBR322 plasmid DNA were studied by spectroscopic, gel electrophoresis and hydrodynamic methods. The apparent binding constant for the interaction with DNA was determined to be 3.97 × 10 3 M − 1 and 4.07 × 10 3 M − 1 at 293 K for 3 and 4 respectively. The complexes bind strongly to HSA with binding constants of 2.94 × 10 4 M − 1 and 12.2 × 10 4 M − 1 at 296 K for 3 and 4 respectively. The in vitro anticancer activity of 3 and 4 has been evaluated against two human colon cancer cell line (HCT-116 and Caco-2) with IC 50 values in the range of 26–150 μM. Both 3 and 4 show good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 μM. The proficiency of 3 and 4 to act as antibacterial agents was also evaluated against six pathogenic bacterial strains with the best activity seen against Gram-positive strains.

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)(2)Ru(TSC)](PF(6))(2) (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2'-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV-Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10(4) M(-1). They are also strong binders of human serum albumin having binding constants on the order of 10(4) M(-1). The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC(50) values range from 7 - 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC(50) values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.

A series of half-sandwich arene-ruthenium complexes of the type [(eta(6)-p-cymene) Ru(thiosemicarbazone)Cl](+) have been synthesized and their biological activity investigated. The first structurally characterized arene-ruthenium half-sandwich complex with a thiosemicarbazone ligand is reported.

The kinetics of the stepwise reduction of the title complex [Fe2(CN)10]4− by sulfite have been studied in the presence of air as a function of pH, sulfite concentration, temperature and ionic strength using stopped-flow and conventional spectrophotometric techniques. The kobs versus pH profile shows a marked increase in rate with increase of pH over the range 3.7 ⩽ pH ⩽ 6.1 due to the increase in concentration of the more reactive sulfite species SO 3 2 - . The reaction proceeds in several stages, the first of which involves a one electron transfer process with the formation of the radical anion SO 3 - This then adds on in a rapid stage to form a species [ Fe 2 III ( CN ) 10 ( SO 3 ) ] 5 - . The second and third stages also involve one electron transfer. In the third, or possibly a fourth stage cleavage occurs, the final product being [FeII(CN)5(SO3)]5−. The reaction rate is sensitive to the nature of the cation present with a reactivity sequence Li + Na + K + NH 4 + .

Deprotonation of gramine with nBuLi and subsequent reaction with PCl3 yielded [(LiCl)6{(Me2NCH2C8H5N)3P}2] (2). Compound 2 was characterized by NMR (1H, 13C, 31P) spectroscopy, elemental analysis, and X-ray crystallography. The molecular structure of 2 reveals a novel hexameric lithium chloride aggregate ligated on each of two hexagonal faces by three dimethylamino groups from the intended product, tris{(3-dimethylamino-methyl)indolyl}phosphine. Crystal data for 2 · 3CH2Cl2: C36H45Cl9Li3N6P, monoclinic, P21/n, a = 12.732(4) A, b = 22.251(6) A, c = 16.815(5) A, β = 108.233(5)°, V = 4525(2) A3, Z = 4, Dcalc = 1.369 g/cm3.