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The aim of this study was to synthesize and characterize a nanogold-{[(Cu)(phen)(cys)(H

Novel Pentaerythritol (PTL)- and dipentaerythritol (DPTL)-cored dendrimer-like star polymers with AB2 miktoarms [A = poly(L-Lactide); poly(ethylene glycol)-folate] (1g and 2g) were synthesized and characterized by proton magnetic resonance spectroscopy, fourier transform infrared, gel permeation chromatography and differential scanning calorimetric techniques. Anticancer drug doxorubicin was encapsulated into the star polymer nanoparticles using nanoprecipitation technique. The doxorubicin-loaded nanoparticles of the star polymer with PTL core (1g-NPs-DOX) and DPTL core (2g-NPs-DOX) were spherical and had average diameters of 185.88 ± 27.53 nm and 203.66 ± 20.69 nm, and zeta potential of −19.54 ± 0.57 mV and − 14.77 ± 1.16 mV, respectively. 2g-NPs-DOX had higher doxorubicin loading and encapsulation efficiency (14.59% ± 0.001; 87.54% ± 0.003) than those of 1g-NPs-DOX (12.88% ± 0.006; 77.29% ± 0.039). In vitro release studies showed that an initial burst release of doxorubicin was followed by a sustained release over 7 days, which were significantly higher at pH 5.3 than at pH 7.4. Both drug-free nanoparticles 1g-NPs and 2g-NPs exhibited low cytotoxic effect against MCF-7 and MCF-10a with over 80% cell viability at maximum concentration (100 μM) after 72 h of incubation. Due to sustained release, the IC50 values (72 h) of 1g-NPs-DOX and 2g-NPs-DOX against MCF-7 cells were 22.5 μM and 19.5 μM respectively, as compared to 41.0 μM and 32.0 μM against MCF-10a cells, which suggested that 1g-NPs-DOX and 2g-NPs-DOX are more effective in inhibiting the breast cancer cell viability. Hence, the dendrimer-like star polymers, 1g and 2g, showed good potential as nanocarriers for preferential delivery of doxorubicin to the breast cancer cells.

The anticancer properties of two previously characterized pairs of optically pure chiral complex salts [Cu(phen)(ala)(H2O)]X·xH2O (phen = 1.10-phenanthroline; X = NO3−; ala: l-alanine (l-ala) 1 and d-alanine (d-ala) 2; and (X = Cl−; ala: l-ala, 3 and d-ala, 4; x = number of lattice water molecules) are reported herein, together with the crystal structure of the d-enantiomer 4. Unlike cisplatin which is ineffective against MCF-7 cancer cells with the absence of caspase-3 protein expression, these two pairs of complex salts were effective against this cell line and they were able to induce an increase in intracellular ROS, loss in mitochondrial membrane potential, cell cycle arrest mainly at SubG1 phase , caspase-9 activation, and caspase-3/caspase-7-independent apoptosis. Screening of 1 on the NCI-60 panel of human cancer cell lines showed that it was effective against most of the cell lines. MTT-NCI modified assay screening was also done on other cancer cell lines, viz. A549, CNE1, and HepG2, and two normal cell lines, viz. MCF-10A and CHANG. The effects of chirality of these Cu(II) compounds, especially the greater selectivity of d-enantiomers over the l-counterparts, on their anticancer properties are also reported herein.

A phenanthroline-based ligand L1 ((((1,10-phenanthrolin-5-yl)imino)methyl)-6-methoxyphenol) was synthesized and reacted with chromium, molybdenum, and tungsten hexacarbonyl to form ultraviolet (UV) activable photoCORMs C1, M1, and T1, respectively. All compounds were characterized via IR, 1H-NMR, 13C-NMR, and CHN elemental analyses, and the X-ray crystal structures of L1 and M1 were determined. The half-life of the photoCORMs decreased with an increasing concentration and the rate of CO release increased in the order of T1

Cancer is a major cause of death worldwide, as exemplified by millions of cancer diagnoses every year. The use of chemotherapy in treating cancer has many disadvantages which include recurrence of cancer, associated with drug resistance, and severe side effects that are harmful to the patients. A better source of anticancer drugs can come from nature. Strobilanthes crispus (S. crispus) is a herbal medicinal plant that is indigenous in Madagascar and the Malay Archipelago. The plant possesses high vitamin and mineral content as well as phytochemicals—like phenols, catechins, tannins, and flavonoids—that are known to have therapeutic effects. Numerous preclinical studies have reported very versatile pharmacological effects of this plant, such as anticancer, antimicrobial, antioxidant, anti-angiogenesis, anti-diabetes, anti-ulcerogenic, and wound healing. Herein, this paper reviews the anticancer properties of S. crispus, providing information for future research and further exploration.

Colorectal cancer (CRC) is the third most common cancer and lethal disease worldwide. Melatonin, an indoleamine produced in pineal gland, shows anticancer effects on a variety of cancers, especially CRC. After clarifying the pathophysiology of CRC, the association of circadian rhythm with CRC, and the relationship between shift work and the incidence of CRC is reviewed. Next, we review the role of melatonin receptors in CRC and the relationship between inflammation and CRC. Also included is a discussion of the mechanism of gene regulation, control of cell proliferation, apoptosis, autophagy, antiangiogenesis and immunomodulation in CRC by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as comprehensive reference for the various mechanisms of action of melatonin against CRC, and as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for CRC.

Chiral enantiomers [Cu(phen)(L-ser)(H2O)]NO31 and [Cu(phen)(D-ser)(H2O)]NO32 (ser = serinato) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(II) complexes, viz. L- and D-[Cu(phen)(OCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; OCA = oxazolidine-4-carboxylate; x = 1/2, 0–2) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. The crystal structures of 1 and 3 showed both the cationic complexes to have a square pyramidal geometry. These complexes were about nine fold more potent than cisplatin against metastatic MDA-MB-231 breast cancer cells, inducing apoptotic cell death via ROS generation and a massive drop in mitochondrial membrane potential. The results of monitoring EZH1, EZH2 and H3K27me3 revealed that the mode of action of 1–4 also involved the downregulation of EZH2 and it seemed to be independent of the H3K27me3 status.

Conjugation of poly(ethylene glycol) (PEG) to poly(lactide-co-glycolide) (PLGA) renders the latter with enhanced biocompatibility and broader overall capability in biomedical application. Novel miktoarm star polymers comprising PLGA and PEG segments are of interest for their potential as drug carriers. Thus, a series of miktoarm star copolymers, PLGA-(mPEG)2, with different PLGA arm molecular weights and methoxy-PEG (mPEG) arm (2000 g/mol), were synthesised via a four-step reaction using carbodiimide chemistry with a low steric hindrance trifunctional linker aminoadipic acid (AAA) and characterised by proton nuclear magnetic resonance (1H NMR), fourier transform infrared (FTIR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Results show that the miktoarm star polymers PLGA17.0-AAA(mPEG)2 and PLGA43.4-AAA(mPEG)2 formed stable nanoparticles and PLGA4.6-AAA(mPEG)2 self-assembled into stable nanomicelles. Fluorescence spectroscopy showed that the critical micelle concentration of PLGA4.6-AAA(mPEG)2 was very low at 6.03 × 10−7 g/mL. Model drug ibuprofen encapsulated nanoparticles and nanomicelles had good drug loading, high encapsulation efficiency, narrow size distribution, and spherical morphology with negative surface charges. The mean particle size increased with increasing PLGA molecular weights, from 37.28 ± 1.03 to 151.5 ± 0.86 nm. In-vitro release of model drug ibuprofen over 7 days from PLGA43.4-AAA(mPEG)2 nanoparticles (61.65 ± 3.04%) was higher than those of PLGA4.6-AAA(mPEG)2 nanomicelles (26.93 ± 1.49%) and PLGA17.0-AAA(mPEG)2 nanoparticles (10.57 ± 0.29%), with all demonstrating controlled release characteristics. In conclusion, the novel miktoarm star polymers PLGA43.4-AAA(mPEG)2 and PLGA17.0-AAA(mPEG)2 and their nanoparticles, and PLGA4.6-AAA(mPEG)2 and its nanomicelles have a great potential as a nanocarrier for controlled delivery of hydrophobic drugs.

The cobalt(II), copper(II) and zinc(II) complexes of 1,10-phenanthroline (phen) and maltol (mal) (complexes 1, 2, 3 respectively) were prepared from their respective metal(II) chlorides and were characterized by FT-IR, elemental analysis, UV spectroscopy, molar conductivity, p-nitrosodimethylaniline assay and mass spectrometry. The X-ray structure of a single crystal of the zinc(II) analogue reveals a square pyramidal structure with distinctly shorter apical chloride bond. All complexes were evaluated for their anticancer property on breast cancer cell lines MCF-7 and MDA-MB-231, and normal cell line MCF-10A, using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and morphological studies. Complex 2 was most potent for 24, 48 and 72 h treatment of cancer cells but it was not selective towards cancer over normal cells. The mechanistic studies of the cobalt(II) complex 1 involved apoptosis assay, cell cycle analysis, dichloro-dihydro-fluorescein diacetate assay, intracellular reactive oxygen species assay and proteasome inhibition assay. Complex 1 induced low apoptosis, generated low level of ROS and did not inhibit proteasome in normal cells. The study of the DNA binding and nucleolytic properties of complexes 1–3 in the absence or presence of H2O2 or sodium ascorbate revealed that only complex 1 was not nucleolytic.

Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]·2H2O, [Cu(phen)(L-leu)Cl]·4½H2O, and [Cu(phen)(L-tyr)Cl]·3H2O, and four binary copper(II) complexes, [Cu(phen)Cl2], Cu(L-phe)2·½H2O, Cu(L-leu)2·½H2O, and Cu(L-tyr)2·H2O (where phen = 110-phenanthroline, L-phe = L-phenylalanine, L-tyr = L-tyrosine, L-leu = L-leucine and Cl- = chloride), were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV–visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, and lipophilicity measurement. X-ray diffraction determination of a single crystal of [Cu(phen)(L-tyr)Cl] showed two independent molecules in the asymmetric unit, each with the same distorted square pyramidal geometry about copper(II). p-Nitrosodimethylaniline assay revealed that the three ternary complexes were better inducers of reactive oxygen species over time than binary complexes, CuCl2, and free ligands. All the copper(II) complexes in this series inhibited the three proteolytic act...

The four copper(II) complexes involving ethylenediamine-N,N-diacetic acid (H2edda) and ethylenediamine (en), viz. [Cu(edda)(en)] H2O 1, [Cu(en)Cl2] 2, [Cu(edda)] 3 and [Cu2(Hedda)2Cl2] 4, were synthesized and characterized by various physical means. The crystal structures of 1 and 4 established them as mononuclear and dichlorido-bridged dicopper(II) complexes respectively. Complexes 1 and 4 showed weak and strong antiferromagnetic Cu…Cu interaction. Dynamic light scattering data of 3 suggested it to be a 3-dimensional coordination polymer in aqueous solution, gel and solid forms. The copper(II) species of 1–4 in aqueous solution were analysed by UV–visible and molar conductivity data. The weak hydroxyl radical-inducing property of free copper(II) ions in solution was enhanced by the chelation of both types of ligands. However, chelation of each or both of these ligands reduce the strong proteasome inhibitory property of the copper(II). All complexes inhibited the three proteolytic sites of the 20S proteasome, with the Trypsin-like site been mostly selectively inhibited.

The d- and l-enantiomers of the ternary complex [Cu(phen)(ala)(H2O)]NO3 [phen = 1,10-phenanthroline; ala = alanine; l-enantiomer (1a); d-enantiomer (1b)] both undergo an aldol-type condensation with formaldehyde under mild acidic conditions to yield racemic rac-[Cu(phen)(4MeOCA)(H2O)(NO3)] (2) (4MeOCA = 4-methyl-oxazolidine-4-carboxylate). The precursors and the products were characterized by circular dichroism, FTIR, UV–Vis, fluorescence spectroscopy, molar conductivity and electrospray ionization mass spectrometry. The racemic nature of the product was established by X-ray crystallography . In the crystal structure, the copper atom has a tetragonally elongated octahedral geometry in which the water and an oxygen atom of a nitrate group are mutually trans. A possible mechanism for the racemization of the ligand is proposed.

The hydrated and anhydrous forms of the copper(II) complex of 3-methylpicolinic acid, monomeric [Cu(3Me-pic) 2 (H 2 O)]·H 2 O 1 and polymeric [Cu(3Me-pic) 2 ] n 2 , were synthesized and characterized by FTIR, UV–visible spectroscopy, conductivity measurement, magnetic susceptibility determination, electron paramagnetic resonance (EPR) and light scattering. Crystal structure analysis of 2 shows that it has a doubly-bridged polymeric structure, involving diagonally stacked Cu(3Me-pic) 2 units which are linked via carbonyl oxygen atoms of the 3Me-pic moieties. Analysis of EPR spectra at 133 K and 293 K suggests isotropic intermolecular spin interaction only in 2 . Complex 2 dissolved in DMF and DMSO solvents to yield nano-size particles. Solution studies show aqueous solutions of 1 and 2 contain the same neutral Cu(3Me-pic) 2 species, which generates less hydroxyl radicals from the reaction with hydrogen peroxide than their precursor CuCl 2 . The Cu(3Me-pic) 2 species exhibit more selective inhibition of the β2 site of the 20S proteasome, among the three proteolytic sites.

A new fluorescent chemosensor (MEK) was synthesized from conjugation of rhodamine B hydrazide and methyl ethyl ketone. It exhibited features that would facilitate the ‘naked-eye’ detection, including excellent selectivity and high sensitivity towards Al3+ and Sn2+ ions. Stronger binding strength was recorded in the formation of sensor-Al3+ complex, where the binding constant (Ka) was 3.58 × 1010 M−1. Detection limits of MEK for Sn2+ and Al3+ was 5.10 μM and 8.96 μM respectively. Moreover, a 1:2 and 1:1 binding stoichiometry between this sensor with Al3+ and Sn2+ was verified via Job’s plot and ESI-MS. Reversibility of the sensor as metal ions detector was evaluated with the introduction of the common quencher EDTA and it showed that MEK can be used repeatedly up to 6 times. Differences in the fluorescence profiles of sensor and the sensor-metal complexes (Al3+ and Sn2+) suggested the possible applications of MEK as detection kit for these metal ions. Interestingly, the on-site assay study shown obvious colour changes and fluorescence, thereby reflecting a potentially useful way in differentiating Al3+ and Sn2+. The combination of significant fluorescence response along with tunable selectivity is therefore notably practical for the application of this sensor.

Discovery and development of antimalarial drugs have long been dominated by single-target therapy. Continuous effort has been made to explore and identify different targets in malaria parasite crucial for the malaria treatment. The single-target drug therapy was initially successful, but it was later supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has warranted a review of current antimalarial pharmacotherapy. This has led to the development of the new concept of covalent biotherapy, in which two or more pharmacophores are chemically bound to produce hybrid antimalarial drugs with multi-target functionalities. Herein, the review initially details the current pharmacotherapy for malaria as well as the conventional and novel targets of importance identified in the malaria parasite. Then, the rationale of multi-targeted therapy for malaria, approaches taken to develop the multi-target antimalarial hybrids, and the examples of hybrid molecules are comprehensively enumerated and discussed.

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements.

In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This ‘fluorine-walk’ analysis revealed that the introduction of fluorine atom at C-5, 6, 5′, or 6′ on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, CF3 and OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50 = 40–85 nM), with the activities surpassing both amphotericin B and miltefosine.

A series of Zn(II) ferrocenylthiosemicarbazones complexes derived from thiosemicarbazide and 4-methyl-, 4-ethyl-, and 4-phenyl-3-thiosemicarbazide were evaluated for their DNA binding propensity and chemical nuclease activity. The equilibrium binding constants, K b, of the complexes for binding with calf thymus DNA (CT DNA) were in the range of 0.68 × 103 to 2.8 × 104 M−1. The complexes do not intercalate into the nucleobases of CT DNA, as evident from viscosity measurements. They exhibit efficient nuclease activity in the absence of an activating agent and cleave supercoiled DNA into nicked and linear circular forms of DNA at very low concentrations.

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.

Four thiosemicarbazones ligands, H3T(1), H3M(2), H3E(3) and H3P(4) have been prepared with good yield by refluxing 2,4-dihydroxybenzaldehyde with N(4)-substituted thiosemicarbazide in ethanol (H3T(1) = 2,4dihydroxybenzaldehyde thiosemicarbazone; H3M(2) = 2,4-dihydroxybenzaldehyde 4-methylthiosemicarbazone; H3E(3) = 2,4-dihydroxybenzaldehyde 4-ethylthiosemicarbazone and H3P(4) = 2,4-dihydroxybenzaldehyde 4-phenylthiosemicarbazone). Reactions of these ligands with zinc acetates in the presence of 2,2

By inhibiting only two or three of 12 restriction enzymes, the series of [M(phen)(edda)] complexes [M(II) is Cu, Co, Zn; phen is 1,10-phenanthroline; edda is N,N'-ethylenediaminediacetate] exhibit DNA binding specificity. The Cu(II) and Zn(II) complexes could differentiate the palindromic sequences 5'-CATATG-3' and 5'-GTATAC-3', whereas the Co(II) analogue could not. This and other differences in their biological properties may arise from distinct differences in their octahedral structures. The complexes could inhibit topoisomerase I, stabilize or destabilize G-quadruplex, and lower the mitochondrial membrane potential of MCF7 breast cells. The pronounced stabilization of G-quadruplex by the Zn(II) complex may account for the additional ability of only the Zn(II) complex to induce cell cycle arrest in S phase. On the basis of the known action of anticancer compounds against the above-mentioned individual targets, we suggest the mode of action of the present complexes could involve multiple targets. Cytotoxicity studies with MCF10A and cisplatin-resistant MCF7 suggest that these complexes exhibit selectivity towards breast cancer cells over normal ones.

A set of copper(II) complexes of glycine and methylated glycine derivatives, Cu(aa)2, consisting of C-dimethylglycine, l-alanine, N-dimethylglycine and sarcosine, was investigated for their DNA binding and nucleolytic properties by means of EPR and visible spectroscopy, and electrophoresis. They bind weakly to DNA with apparent binding constants in the range 1.8–2.9 × 103 M−1 with very similar orientation. No DNA cleavage is observed in the absence of exogenous agents. Copper(II) complexes of N-methylated derivatives bind to DNA more stereo-specifically and less strongly, and their oxidative DNA cleavage is less efficient than those of the corresponding C-methylated derivatives in the presence of hydrogen peroxide (H2O2) alone, or sodium ascorbate (NaHA) alone or tandem H2O2–NaHA. The oxidative DNA cleavage mechanism in the three systems involves a common copper(I) species. Neocuproine can inhibit DNA cleavage by these complexes.

Three water soluble dicopper(II) complexes, tetrakis(μ-4-chloro-2-nitrobenzoato-κ2O,O′) bis[aquacopper(II)] (1), tetrakis(μ-2-chloro-6-fluorobenzoato-κ2O,O′)bis[aquacopper(II)] (2) and tetrakis(μ-2-chlorobenzoato-κ2O,O′)bis[aquacopper(II)] (3), have been synthesized. Complex 1 crystallizes in monoclinic system, space group C2/c with a = 28.813(3), b = 7.2368(6), c = 17.0053(14) A, β = 105.395° and Z = 4, while 2 crystallizes in triclinic system, space group P 1 ¯ with a = 7.5638(2), b = 13.0494(4), c = 16.7079(5) A, α = 106.003°, β = 90.388°, γ = 91.855° and Z = 2. In addition, all the complexes have been characterized by their elemental analysis, FT-IR, UV–Vis spectroscopy and cyclic voltammetry. All complexes have been found to be redox active displaying two quasi-reversible redox couples corresponding to CuIICuII to CuIICuI and CuIICuI to CuICuI redox processes, respectively. The results from the gel electrophoresis experiment of 1–3 on pBR322 DNA, have demonstrated the occurrence of oxidative cleavage in the presence of hydrogen peroxide. The hydroxyl radical has been found to be the reactive oxygen species that is responsible for the cleavage reaction. In the antiproliferation tests against MCF-7, DU 145, HeLa and HepG2 cancer cell lines, all complexes show significant preference against HepG2 cell lines. All complexes also show significant preference against HepG2 cancer cells line over Chang human normal liver cells which means 1–3 are more potent against cancer cells than normal cells. In antibacterial tests against nine pathogenic bacterial species, all complexes show a very selective trend whereby they exhibit antibacterial activity against the Gram negative bacteria Enterobacter aerogenes.

A series of ternary metal(ii) complexes {M(phen)(edda); 1a (Cu), 1b (Co), 1c (Zn), 1d (Ni); H(2)edda = N,N(')-ethylenediaminediacetic acid} of N,N'-ethylene-bridged diglycine and 1,10-phenanthroline were synthesized and characterized by elemental analysis, FTIR, UV-visible spectroscopy and magnetic susceptibility measurement. The interaction of these complexes with DNA was investigated using CD and EPR spectroscopy. MTT assay results of 1a-1c , screened on MCF-7 cancer cell lines, show that synergy between the metal and ligands results in significant enhancement of their antiproliferative properties. Preliminary results from apoptosis and cell cycle analyses with flow cytometry are reported. seems to be able to induce cell cycle arrest at G(0)/G(1). The crystal structure of 1a is also included.

Like chiral organic drugs, the chemical and biological properties of metal complexes can be dependent on chirality. Two pairs of [Cu(phen)(ala)(H2O)]X·xH2O (phen=1.10-phenanthroline: X=NO3(-); ala: l-alanine (l-ala), 1 and d-alanine (d-ala) 2; and (X=Cl(-); ala: l-ala, 3 and d-ala, 4) complex salts (x=number of lattice water molecules) have been synthesized and characterized. The crystal structure of 3 has been determined. The same pair of enantiomeric species, viz. [Cu(phen)(l-ala)(H2O)](+) and [Cu(phen)(d-ala)(H2O)](+), have been identified to be present in the aqueous solutions of both 1 and 3, and in those of both 2 and 4 respectively. Both 3 and 4 bind more strongly to ds(AT)6 than ds(CG)6. There is no or insignificant effect of the chirality of 3 and 4 on the production of hydroxyl radicals, binding to deoxyribonucleic acid from calf thymus (CT-DNA), ds(CG)6, G-quadruplex and 17-base pair duplex, and inhibition of both topoisomerase I and proteasome. Among the three proteasome proteolytic sites, the trypsin-like site is inhibited most strongly by these complexes. However, the chirality of 3 and 4 does affect the number of restriction enzymes inhibited, and their binding constants towards ds(AT)6 and serum albumin.

M(edda) complexes (Cu, Co, Ni, Zn) have been characterized by UV–visible spectroscopy and ESI-MS to study the species in aqueous solution. The Co complex crystallizes as the octahedral diaqua(N,N′-ethylenediaminediacetato)cobalt(II) monohydrate and its crystal structure is reported. Cu(edda) cleaves plasmid DNA in the presence of hydrogen peroxide better than Co(edda) while the Zn and Ni analogues are inactive. Partial and complete inhibition of DNA cleavage can be effected by radical scavengers and Na2H2EDTA, respectively. The cleavage efficiency of Cu(edda) varies with the concentration of the complex, pH of the buffer and the type of buffer. The difference in nucleolytic efficiency of Cu(edda) and other complexes studied can be explained by the difference in amount of OH radicals produced, as determined by a PNDA assay. ESI-MS and CD studies on the Cu(edda) complex confirms its binding to DNA and results in a non-denaturational type of conformation change.

Aquabis(N,N-dimethylglycinato)copper(II) dihydrate, [Cu(dmg)2(H2O)]·2H2O, has been synthesized and characterized by elemental analysis, FT-IR, magnetic data, thermal analysis, solution UV-visible spectroscopy, X-ray crystal structure analysis and electrospray ionization mass spectroscopy. The square pyramidal copper(II) complex crystallizes in the orthorhombic space group P212121. The complex cleaves circular plasmid DNA (pBR322) in the presence of H2O2. The extent of cleavage varies with the concentration range of the complex, the type of buffer used, pH of buffer and the concentration of H2O2. Hydroxyl radical scavenger can inhibit the nucleolytic ability of this complex.

The Mannich aminomethylation of bis( l -alaninato)copper(II), Cu( l -ala)2, with formaldehyde and acetamide yields the bis[N-(N′-methylacetamido)- l -alaninato]copper(II) (1) and bis[N,N-di-(N′-methylacetamido)- l -alaninato]copper(II) (2) complexes. The crystal structure of 2 shows the amide N–H of the uncoordinated N-methylacetamido substituents and that of the coordinated N-methylacetamido substituents forming intra- and inter-molecular hydrogen bonding. Both complexes have been characterized by elemental analysis, UV–Vis spectroscopy, magnetic susceptibility measurements and EI mass spectroscopy. A gel electrophoresis experiment on the soluble complex 1 in Tris–NaCl buffer at pH 8.3, from which 2 is formed, shows oxidative cleavage of DNA by 1 in the presence of hydrogen peroxide. The cleavage efficiency of 1 is greater than that of its precursor, Cu( l -ala)2.

The crystal structure of a centrosymmetric dinuclear nickel(II) complex, formed from the reaction of bis(L-alaninato)nickel(II) with formaldehyde and methylamine, shows two bridging 2,4,8,10-tetramethyl-5-oxido-5′-carboxylato-2λ5,4,8,10-tetraazaspiro[5.5]undec-2-en(234-del)-ylium ligands, L, and two formato ligands; each nickel atom exists in a trans-N2O4 octahedral geometry with an average (μ-O)–Ni distance of 2.033(1) A and Ni···Nii distance of 2.894(1) A. Formation of L implicates an unprecedented deamination step involving activation of both the α-carbon and the α-methyl hydrogen atoms of the L-alaninato moiety.

In its crystal structure, mer-tris(β-alaninato)cobalt(III), mer-[Co(β-ala)3], assumes a half-chair conformation. The complex has been additionally characterized by UV–Vis spectroscopy on its buffered solutions, electrospray ionization-mass spectroscopy (ESI-MS) and cyclic voltammetry. Its larger λmax value (visible region) compared to cobalt(III) complexes of α-amino acids suggests that β-alaninate is a weaker field ligand. Compared to CoIII hexamine complexes with six nitrogen-ligating atoms, mer-[Co(β-ala)3], with a N3O3 coordination sphere, is more easily reduced. The complex alone does not cleave DNA but can do so in the presence of ascorbic acid in TBE buffer pH 8.3. DNA cleavage can be attributed to ascorbate free radicals generated by one-electron transfer from ascorbate ions to mer-[Co(β-ala)3]. This represents the first report of DNA cleavage by a cobalt chelated amino acid complex.