Georgia M. Arvanitis

Synthesis, characterization and antitumor activity of platinum triamine complexes containing imidazothiazole ligands

Abstract A series of platinum(II) and platinum(IV) triamine complexes was prepared, characterized and evaluated as potential antitumor agents. The complexes were cis or trans isomers of the form [PtA 2 (N-het)Cl] + or [PtA 2 (N-het)Cl 3 ] + , where A is the monodentate amine, NH 3 , or A 2 is the bidentate amine, ethylenediamine (en), and N-het is an imidazothiazole or a derivative. The structures of two of the platinum complexes, [Pt(en)(C 5 H 6 N 2 OS)Cl]NO 3 ( 5b ) and [Pt(en)(C 5 H 6 N 2 OS)Cl 3 ]NO 3 ( 5e ), were determined by single-crystal X-ray diffraction. Crystals of complex 5b were orthorhombic in space group Pna2 1 , a = 9.2451(7), b = 18.950(2), c = 7.908(2) A , Z = 4 . Those of complex 5e were triclinic in space group P(−1), a = 8.2884(9), b = 10.853(1), c = 11.244(2) A , α = 72.50(1), β = 70.42(1), Z = 2 . Biological activity was measured by in vitro assay against S180, L1210 and L1210/DDP cell lines, and IC 50 values were calculated by linear regression analysis of the data. Results from these preliminary screens indicate that compounds having cis ammine groups are more active than those with the trans arrangement, consistent with prior observations. Complexes with ligands derived from benzimidazole moieties displayed promising cytotoxicity in vitro. Furthermore, this work shows that cytotoxic complexes were not restricted to compounds with planar ligands, in contrast to previous reports. Platinum(IV) derivatives were as active or more active than their Pt(II) analogues.

Ternary Pt(II)-amino acid-nucleotide complexes: kinetics of formation

Abstract Ternary complexes of Pt(II) with the nucleotides 5′-GMP, 3′-GMP and 5′-dGMP (GMP=guanosinemonophosphate), and with the amino acids N α -BOC L -histidine, N α -BOC- L -methionine and 1-methylimidazole (1-MeIm) were studied as models for Pt mediated DNA-protein crosslinks. The triamine complexes [PtAm 2 (L)Cl] + (where Am 2 =cis- or trans -(NH 3 ) 2 or ethylenediamine and L=1-MeIm or N α -BOC- L -his- N 3) react readily with the mononucleotides 5′-GMP, 3′-GMP and 5′-dGMP to form the ternary crosslinked complexes PtAm 2 (L)(nucleotide). The 5′-nucleotides react faster than their 3′ counterparts towards either triamine complex. Kinetic studies by 1 H NMR show that cis -[PtAm 2 (1-MeIm- N 3)Cl] + reacts with 5′-GMP faster than the trans isomer (second order rate constants k 2 =0.756 and 0.358 M −1 s −1 , respectively) and that the ethylenediamine complex is faster than both ( k 2 =1.09 M −1 s −1 ).

SYNTHESIS OF TWO TETRAPHENYLANTIMONY COMPLEXES OF PYRIDINE-N-OXIDES; CRYSTAL STRUCTURE OF TETRAPHENYLANTIMONY (2-MERCAPTOPYRIDINE-N-OXIDE)

Abstract Tetraphenylantimony(2-mercaptopyridine-N-oxide) and tetraphenylantimony(2-selenopyridine-N-oxide) were synthesized from tetraphenylantimonybromide and the appropriate pyridine-N-oxide derivative. X-ray crystal structure analysis shows that the former compound crystallizes in space group C2/c. with a 29.095(2), b 10.6965(8). c 18.134(1). β 94.154(5) and Z 8. The mercaptopyridine-N-oxide ligand binds via both its sulfur and oxygen atoms, leading to a distorted octahedral geometry about the antimony atom. Tetraphenylantimonypyridine-N-oxide derivatives of sulfur and selenium were found to possess antimalarial activity.

(+ac,-ac)-trans-Bis(hinokitiolato)copper(II) and its chloroform disolvate.

The complex trans-bis(hinokitiolato)copper(II) [systematic name: trans-bis(3-isopropyl-7-oxocyclohepta-1,3,5-trienolato)copper(II); abbreviated name: trans-Cu(hino)2], [Cu(C10H11O2)2], is a biologically active compound. Three polymorphs of this square-planar monomer, all with (+sp,-sp) isopropyl substituents, have been reported previously. A fourth polymorph containing (+ac,-ac) isopropyl groups and its chloroform disolvate, [Cu(C10H11O2)2].2CHCl3, both exhibiting nonmerohedral twinning and with all Cu atoms on centers of crystallographic inversion symmetry, are reported here. One of the differences between all of these polymorphs is the relative conformation of the isopropyl groups with respect to the plane of the molecule. Stacking and Cu...olefin pi distances ranging from 3.214 (4) to 3.311 (2) A are observed, and the chloroform solvent molecules participate in bifurcated C-H...O hydrogen bonds [H...O = 2.26-2.40 A, C...O = 3.123 (5)-3.214 (5) A, C-H...O = 127-151 degrees and O...H...O = 74 degrees].

Two new polymorphs of trans-bis(hinokitiolato)copper(II).

The title complex [systematic name: trans-bis(3-isopropyl-7-oxocyclohepta-1,3,5-trienolato)copper(II)], [Cu(C10H11O2)2], is a substance possessing antimicrobial activity. The compound crystallizes in a number of polymorphic forms, the structures for two of which are reported here. Stacks of square-planar molecules exhibiting weak intermolecular copper-olefin pi interactions (not observed in earlier reports on this substance) are described. The molecules have crystallographically imposed inversion symmetry, with stacking and copper-olefin pi distances ranging from 3.226 (2) to 3.336 (1) A.

cis-Dichloro(dimethyl sulfoxide-S)-(2-methoxypyridine-N)platinum(II)

The title complex, [PtCl(2)(C(6)H(7)NO)(C(2)H(6)OS)], exhibits square-planar geometry. The plane of the pyridine ring makes a dihedral angle of 67.2 (3) degrees with the square plane of the metal center. The S-O bond is nearly aligned with the adjacent Pt-N bond, leaving the methyl groups of the dimethyl sulfoxide ligand to stagger the Pt-Cl bond.

Structure of bis(2-pyridine-N-oxide) diselenide and its formation from tetraphenylantimony(V)selenopyridine-N-oxide

AbstractThe structure of bis(2-pyridine-N-oxide) diselenide was determined by single crystal X-ray diffraction. The compound crystallized in the triclinic system and the structure was solved in the space group

Structure of a platinum(II) complex of levamisole.

P\bar 1