Exploration of selected electronic characteristics of half-sandwich organoruthenium(II) ß-diketonate complexes.

Based on experimental work, 12 half-sandwich organoruthenium(II) complexes with p-cymene and various substituted ß-diketonates (acac) modified by several functional groups were explored. These complexes were optimized at the B3PW91/6-31 + G(d)/PCM/UFF computational level with the Ru atom described by Stuttgart pseudopotentials. The electron density analysis was performed using the B3LYP/ 6-311++G(2df,2pd)/DPCM/scaled-UAKS model. Electrostatic and averaged local ionization potential were explored and extremes on 0.001 e/a.u.3 isodensity surfaces discussed. Natural population analysis partial charges and electron densities in bond critical point of the key Ru(II) coordination bonds were determined. There was a clear correlation between the results obtained and experimentally known anticancer descriptors. Graphical abstract Top Average local ionization potential (ALIP) of half-sandwich organoruthenium(II) ß-diketonate complex, bottom IC 50 of b-series for ovarian cancer and Ru-P distances (in Å).

Guanine bases in DNA G-quadruplex adopt nonplanar geometries owing to solvation and base pairing.

The effect of base pairing and solvation on pyramidalization of the glycosidic nitrogen found in the residues of parallel G-quadruplex with NDB ID UDF062 is analyzed and explained with theoretical calculations. The extent of the pyramidalization depends on the local geometry of the 2'-deoxyguanosine residues, namely on their glycosidic torsion and sugar pucker, which are predetermined by the 3D-architecture of G-quadruplex. Pyramidal inversion of the glycosidic nitrogen found in 2'-deoxyguanosines of G-quadruplex is induced owing to site-specifically coordinated solvent. Different adiabatic structural constraints used for fixing the base-to-sugar orientation of 2'-deoxyguanosine in geometry optimizations result in different extents of pyramidalization and induce pyramidal inversion of the glycosidic nitrogen. These model geometry constraints helped us analyze the effect of real constraints represented by explicit molecular environment of selected residues of the G-quadruplex. The maximal extent of the glycosidic nitrogen pyramidalization found in the high-resolution crystal structure corresponds to the calculation to deformation energy of only 1 kcal mol(-1). The out-of-plane deformations of nucleobases thus provide a way for compensating the site-specific external environmental stress on the G-quadruplex.

Correlating the 31P NMR chemical shielding tensor and the 2J(P,C) spin-spin coupling constants with torsion angles ζ and α in the backbone of nucleic acids.

Determination of nucleic acid (NA) structure with NMR spectroscopy is limited by the lack of restraints on conformation of NA phosphate. In this work, the (31)P chemical shielding tensor, the Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and the (2)J(P,C3'), (2)J(P,C5'), and (3)J(P,C4') coupling constants were calculated in dependence on NA backbone torsion angles ζ and α. While the orientation of the (31)P chemical shielding tensor was almost independent of the NA phosphate conformation, the principal tensor components varied by up to ~40 ppm. This variation and the dependence of the phosphate geometry on torsion angles ζ and α had only a minor influence on the calculated Γ(P,C5'H5'1) and Γ(P,C5'H5'2) cross-correlated relaxation rates, and therefore, the so-called rigid tensor approximation was here validated. For the first time, the (2)J(P,C) spin-spin coupling constants were correlated with the conformation of NA phosphate. Although each of the two J-couplings was significantly modulated by both torsions ζ and α, the (2)J(P,C3') coupling could be structurally assigned to torsion ζ and the (2)J(P,C5') coupling to torsion α. We propose qualitative rules for their structural interpretation as loose restraints on torsion angles ζ and α. The (3)J(P,C4') coupling assigned to torsion angle ß was found dependent also on torsions ζ and α, implying that the uncertainty in determination of ß with standard Karplus curves could be as large as ~25°. The calculations provided a unified picture of NMR parameters applicable for the determination of NA phosphate conformation.