Joze Koller

Development and Validation of Empirical Force Field Parameters for Netropsin

The netropsin molecule preferentially binds to the four consecutive A.T base pairs of the DNA minor groove and could therefore inhibit the expression of specific genes. The understanding of its binding on a molecular level is indispensable for computer-aided design of new antitumor agents. This knowledge could be obtained via molecular dynamics (MD) and docking simulations, but in this case appropriate force field parameters for the netropsin molecule should be explicitly defined. Our parametrization was based on the results of quantum chemical calculations. The resulting set of parameters was able to reproduce bond lengths, bond angles, torsional angles of the ab initio minimized geometry within 0.03 A, 3 deg and 5 deg, respectively, and its vibrational frequencies with a relative error of 4.3% for low and 2.8% for high energy modes. To show the accuracy of the developed parameters we calculated an IR spectrum of the netropsin molecule using MD simulation and found it to be in good agreement with the experimental one. Finally, we performed a 10 ns long MD simulation of the netropsin-DNA complex immersed in explicit water. The overall complex conformation remained stable at all times, and its secondary structure was well retained.

Copper(II) carboxylates with 4-aminopyridine: neutral mononuclear structures, isomerism of aceto compounds and a novel tetranuclear structure

Reactions of copper(II) carboxylates with 4-aminopyridine (4-apy) were investigated and their products structurally characterized by single crystal X-ray diffraction. Reaction of copper(II) acetate resulted in two isomers of a monomeric complex of composition Cu(ac)2(4-apy)2 with markedly different stabilities: the violet form, 1, unstable in air and the blue, stable form, 2. In both isomers the ligands are arranged around the copper atom in a trans geometry. The 4-apy ligands lie almost in the plane in 1, while they are twisted with respect to each other in 2. Variations were observed also in the coordination of the acetate groups to the copper ion. The energy difference between the two isomers was obtained on the basis of ab initio MO calculations. The result agrees well with the observed relative stabilities in the solid state. Monomeric complexes of the same stoichiometry were obtained also by the reaction of Cu(II) hexanoate and heptanoate with 4-apy. The violet Cu(hex)2(4-apy)2, 3, and Cu(hep)2(4-apy)2, 4, are isostructural and possess trans geometry of the ligands around the copper centre. Reaction of 4-apy with Cu(II) octanoate lead to formation of a novel, unprecedented basic centrosymmetric tetranuclear compound of composition Cu4(oct)6(OH)2(4-apy)2, 5. Complex 5 contains bidentate bridging and monoatomic bridging carboxylate groups, triply bridging hydroxyl groups and 4-aminopyridine as a terminal ligand. In all five compounds 4-apy is coordinated through the endocyclic nitrogen atom only.

The search for protonated dihydrogen trioxide (HOOOH): insights from theory and experiment.

Protonated dihydrogen trioxide (HOOOH) has been postulated in various forms for many years. Protonation can occur at either the terminal (HOOO(H)H(+)) or central (HOOH(OH)(+)) oxygen atom. However, to date there has been no definitive evidence provided for either of these species. In the current work we have employed ab initio methods, CCSD(T) and MP2, with a large basis set (6-311++G(3df,3pd)) to determine the relative stabilities of these species. It is shown that the terminally protonated species is strongly favored relative to the centrally protonated species (DeltaE = 15.8 kcal/mol, CCSD(T)//MP2). The mechanism of formation of HOOO(H)H(+) was determined to occur with a low barrier with the H(3)O(+) occurring in a thermoneutral reaction (DeltaE = -0.3 kcal/mol, CCSD(T)//MP2). Although HOOO(H)H(+) exists as a stable intermediate, it is extremely short-lived and rapidly decomposes (DeltaE* = 8.6 kcal/mol, MP2) to H(3)O(+) and O(2)((1)Delta(g)). The decomposition reaction is stabilized by solvent water molecules. The short-lived nature of the intermediate implies that the intermediate species can not be observed in (17)O NMR spectra, which has been demonstrated experimentally.

Deuteron quadrupole coupling constants in crystals with symmetrical hydrogen bonds

Deuteron quadrupole coupling constants for the free formic and trifluoroacetic acid molecules, for their acid anions and for the maleate anion were calculated using the INDO method. The results are compared with experimental values for potassium deuterium maleate and bistrifluoroacetate.