Marek Fronc

1. Copper ions play a vital role in numerous biological processes. The interaction between copper ions and drugs used for therapy is a topic of significant interest [1]. Copper(II) ions are vital f...

The experimental electron density distributions in two coordination compounds – one with a central Cu(I) atom and the other with Cu(II), coordinated by the same biphenyldiimino dithioether (bite) type of ligand – have been obtained from high-resolution X-ray reflection data to model the possible electron predisposition for the redox reaction in blue copper proteins. The bite ligand has been adapted to the conformation required by the central atom.

The experimental electron density distribution in two coordination compounds, one with a central atom Cu(I) and the other with Cu(II), coordinated by the same biphenyldiimino dithioether-type ligand (bite) has been obtained from high-resolution X-ray diffraction data to model the possible electron predisposition for the redox reaction in blue copper proteins. The bite ligand has been adapted to the conformation required by the central atom

The experimental electron density distribution in two isostructural and isomorphous complexes, tetrakis(μ₂-acetato)diaquadicopper(II) [H₂OCu(ac)₂Cu(ac)₂H₂O] (I) and tetrakis(μ₂-acetato)diaquadichromium(II), [H₂OCr(ac)₂Cr(ac)₂H₂O] (II), has been obtained from high-resolution X-ray diffraction data in order to shed light on the bonding properties in the compounds studied. It has been shown that from accurate X-ray data it is possible to discuss the bonding capability of the metal atom (Cu/Cr) and the ligands in these complexes. A comparison of results obtained from averaged and non-averaged X-ray data demonstrates that using the non-averaged data and introducing an anisotropic correction for secondary extinction errors provides a more detailed distribution of the electron density in the area of the metal atoms. In both complexes studied, the bonding of the acetate oxygen atom to the central metal atom is significantly affected by the formation of hydrogen bonds. The electron density and its Laplacian at the bond critical point of metal–oxygen coordination bonds for those oxygen atoms not involved in the intermolecular hydrogen bonds are approximately 10% larger compared with the case when oxygen atoms take part in hydrogen bonds with the neighboring water molecules. It is shown that metal–oxygen bonds in a quasi-equatorial plane are typical coordination bonds and differ significantly from the apical metal–oxygen bond. Metal–metal interaction with a small positive value of the electron density Laplacian at this bond critical point is mainly of electrostatic character. The metal–metal interaction is definitely not a bond according to the classical definition. Based on a search of the Cambridge Structural Database, it can be argued that there are four typical coordination bonds in the [CuO₆] chromophore, similar to the four Cu—O coordination bonds in the basal plane of the CuO₅ pyramid in one of the complexes under study.

A modification of biphenylyltetrazole moiety of Losartan (A) by 3-(2-heteroaryl)-pyrazolotetrazole (B) is described. Ketone semicarbazones react with two moles of phosphorus oxychloride-dimethylformamide with the formation of 3-substituted pyrazol-4-carbaldehydes. The transformations of 3-substituted pyrazole-4- carboxaldehydes to 3-substituted pyrazole-4-nitriles were carried out by reaction of hydroxylamine in DMFA. The prepared cyano pyrazoles were converted to tetrazoles by heating with trimethylsilylazide and dibuthyltinoxide in toluene.

The synthesis of isoxazolidinyl nucleosides based on the Vorbrüggen nucleosidation of 5-acetoxyisoxazolidines 5 and 9 is reported. The 1,3-dipolar cycloaddition of d-erythro-nitrone 4 with vinyl acetate proceeded with respectable anti-facial (84:16) and endo-facial (72:28) diastereoselectivity to give the diastereomeric isoxazolidines 5-7. The reaction of d-threo-nitrone 8 with vinyl acetate is more selective and proceeds with excellent anti-facial preference producing only two diastereomers 9 and 10, although four diastereomers are possible. The condensation of the acetoxyisoxazolidines 5 and 9 with silylated uracil, thymine, N-acetylcytosine, N ²-acetylguanine, and purines proceeded with moderate to excellent stereoselectivity with formation of the expected isoxazolidinyl β- and α-nucleosides. The stereoselectivity of the addition of silylated nucleobase is depended on the structure of the substituent at C3 originating from the starting chiral nitrone and on the attacking nucleobase.