Novel Pt(II) complexes containing pyrrole oxime, synthesis, characterization and DNA binding studies

Since the discovery of anticancer activity and subsequent clinical success of cisplatin (cis-[PtCl2(NH3)(2)]), platinum-based compounds have since been widely synthesized and studied as potential chemotherapeutic agents. In this sense, three novel nuclease active Pt(II) complexes with general formula; [Pt(NH3)CI(L)] (1), [Pt(L)(2)] (2), and K[PtCl2(L)] (3) in which L is 1-H-pyrrole-2-carbaldehyde oxime were synthesized. Characterization of complexes was performed by elemental analysis, FT-IR, H-1 NMR and mass spectroscopy measurements. Interaction of complexes (1-3) with calf thymus deoxyribonucleic acid (ct-DNA) was investigated by using electrochemical, spectroelectrochemical methods and cleavage studies. The hyperchromic change in the electronic absorption spectrum of the Pt(II) complexes indicates an electrostatic interaction between the complexes and ct-DNA. Binding constant values between 4.42 x 10(3) and 5.09 x 10(3) M-1 and binding side size values between 2 and 3 base pairs were determined from cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies

Simultaneous novel synthesis of conducting and non-conducting halogenated polymers by electroinitiation of (2,4,6-trichloro- or 2,6-dichlorophenolato)Ni(II) complexes

NiL2(Ph)(2)(.)xH(2)O [L=3,5-dimethylpyrazole or N-methyl imidazole; Ph=DCP or TCP; x=0, 1 or 3] complexes were synthesised and characterised by analytical and spectroscopic methods using elemental analysis and FTIR. The electrochemical behavior of the complexes was studied by cyclic voltammetry in tetrabutylammoniumtetrafluoroborate-N,N-dimethylformamide electrolyte-sol vent couple. Cyclic voltammogram of the complexes displayed two-step oxidation processes under the nitrogen gas atmosphere. The polymerization of the complexes was accomplished in the same solvent-electrolyte couple by the constant potential electrolysis of NiL2(Ph)(2)(.)xH(2)O, synthesizing the poly(di- or monochlorophenylene oxide)s via free radical mechanism. The simultaneous polymerization of non-conducting polymer and conducting polymer (the conductivity of 0.7 S cm(-2)) were achieved by electroinitiated polymerization of Ni(DMPz)(2)(TCP)(2). The structural analysis of the polymers were performed using FTIR, H-1 NMR and C-13 NMR spectroscopic techniques and DSC for the thermal analysis. The kinetics of the polymerization was followed by in situ UV-vis spectrophotometer during the electrolysis. The low temperature ESR spectrum of the electrolysis solution also confirmed the formation of phenol radical (g=2.0028). One electron oxidation process of NiL2(DCP)(2)(.)xH(2)O produces a new Ni(II) complex, Ni(L-L)(DCP)(2)(S) by the rapid decomposition of (NiL2)-L-III(DCP)(2) into a ligand radical producing a singlet with the g value of 2.0015. Second electron oxidation process generates oligemers, which could not be isolated from the electrolyte solution

Interaction of a novel platinum drug with bovine serum albumin: FTIR and UV-Vis spectroscopy analysis

Platinum complexes have proven to be very effective in cancer treatment. However, severe side effects of these drugs have lead scientists to pursue new platinum complex derivatives. A novel blue platinum compound, called Platinum-Blue (Pt-Blue), is one of the promising candidate platinum compounds to be used for tumor treatment. In this study, the interaction of Pt-Blue with bovine serum albumin (BSA) has been investigated using UV-Vis and FTIR spectroscopy. One of the findings is that the drug-protein interaction type depends on the drug concentration. Though Pt-Blue is attached to the surface of BSA at high concentrations, it interacts with a hydrophobic region of the protein at low concentrations with a binding constant of 1.93 x 10(5) M-1. Spectroscopic results indicate the hydrophobic docking position to be around Trp 213 in domain II, which is surrounded by a number of Asp and Glu. During this interaction, helices such as helix-10, helix-18, helix-19 and helix-24 change orientation and/or partially unfold to make room for the compound. Binding constants at high and low concentrations of Pt-Blue are determined using UV-Vis spectroscopy, which are found to be comparable to cisplatin. FTIR spectroscopy also reveals that the interaction between Pt-Blue and BSA is noncovalent, which makes the candidate drug favorable because it is available for DNA binding while being carried by albumin

Electrochemical and quantum chemical studies on mitomycin and adriamycin

In-situ spectroelectrochemical redox behaviour of two prominent chemotherapeutic agents, mitomycin and adriamycin were studied at constant potential. AM 1 (UHF) type quantum chemical calculations on the neutral as well as radical anion and cation forms of mitomycin and adriamycin were performed

Electrochemistry of nickel(II) complexes with N,N'-bis(3,5-di-tert-butylsalicylidene)polymethylenediamines

The electrochemical oxidation of several N,N'-polymethylenebis(3,5-di-tert- butylsalicylaldiminato)nickel(II) complexes, Ni(L-x), has been studied by cyclic voltammetry and in situ UV-Vis spectroscopy in DMF Cyclic voltammograms of Ni(L-x) (x = 1-4) complexes displayed two-step oxidation processes under nitrogen gas atmosphere. The first oxidation peak potentials of all the Ni(II) complexes corresponds to the reversible one-electron oxidation process of the metal center, yielding Ni(III) species. EPR spectrum of the electrolysis solution was recorded after one electron transfer at liquid nitrogen temperature also confirms the formation of [Ni-III (L-3)](+) species (g(x) > g(y) > g(z)) with a (2)A(1)(d(z)(2))(1) ground state. Upon addition of pyridine to one electron oxidised solutions a new penta coordinated species, [Ni-III(L-3)Py](+) (g(perpendicular to) > g(parallel to), a(parallel to)(N-14) = 8 G), was produced. The second oxidation peak of the complexes was assigned as the ligand based oxidation, generating a coordinated phenoxy radical species

Spectroelectrochemical Investigation of Nuclease Active Pt(II) Complexes Containing Pyrrole Oxime

In this paper, the electrochemical oxidation of three Pt(II) complexes containing pyrrole oxime (HL) having a general formula of [Pt(NH3)Cl(L)] (1), [Pt(L)(2)] (2), and K[PtCl2(L)] (3) has been investigated by in-situ spectroelectrochemistry in dimethylformamide (DMF). An irreversible metal-based oxidation process occurs during the anodic scan for each of the three complexes. The electronic absorption spectral changes indicate that all the three complexes generate similar Pt(IV) compounds and free ligand. Our experimental data is supported by quantum chemistry calculations utilizing density functional theory. In addition, the frontier orbital energy distributions indicate that electron densities are localized on mainly platinum atom

Concise synthesis, electrochemistry and spectroelectrochemistry of phthalocyanines having triazole functionality

The synthesis of novel metallophthalocyanines (M = Zn, Ni) bearing substituted benzyl protected 1,2,3-triazole moieties at peripheral positions is described for the first time via direct cyclotetramerization. These complexes have been characterized by a combination of FT-IR, H-1 NMR, HRMS and UVVis spectroscopy techniques and all the new compounds are highly soluble in most common organic solvents. In addition, the electrochemical and electrochromic behaviors of the complexes are investigated. Cyclic voltammetry and differential pulse voltammetry measurements demonstrate ligand base oxidations and reductions for both the Zn(II) and Ni(II) phthalocyanines by the transfer of one electron in each electrochemical step. The redox couples are identified in situ by monitoring the electronic absorption spectral changes during the electrolysis

Platinated copper(3-clip-phen) complexes as effective DNA-cleaving and cytotoxic agents.

The synthesis and biological activity of three heteronuclear platinum-copper complexes based on 3-Clip-Phen are reported. These rigid complexes have been designed to alter the intrinsic mechanism of action of both the platinum moiety and the Cu(3-Clip-Phen) unit. The platinum centers of two of these complexes are coordinated to a 3-Clip-Phen moiety, an ammine ligand and two chlorides, which are either cis or trans to each other. The third complex comprises two 3-Clip-Phen units and two chloride ligands bound in a trans fashion to the platinum ion. DNA-cleavage experiments show that the complexes are highly efficient nuclease agents. In addition, a markedly difference in their aptitude to perform direct double-strand cleavage is observed, which appears to be strongly related to the ability of the platinum unit to coordinate to DNA. Indeed, complex 6 is unable to coordinate to DNA, which is reflected by its incapability to carry out double-strand breaks. Nonetheless, this complex exhibits efficient DNA-cleavage activity, and its cytotoxicity is high for several cell lines. Complex 6 shows better antiproliferate activity than both cisplatin and Cu(3-Clip-Phen) toward most cancer cell lines. Furthermore, the cytotoxicity observed for 1 is for most cell lines close to that of cisplatin, or even better. Cu(3-Clip-Phen) induces very low cytotoxic effects, but a marked migratory activity. Complex 6 presents DNA-cleavage properties comparable to the one of Cu(3-Clip-Phen), but it does not show any migratory activity. Interestingly, both Cu(3-Clip-Phen) and 6 induces vacuolisation processes in the cell in contrast to complex 1 and cisplatin. Thus, the four complexes cisplatin tested, Cu(3-Clip-Phen), 1 and 6 stimulate different cellular responses.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe