Background: Cisplatin (CisPt) has a well-recognized anticancer activity by interacting with DNA and inducing programmed cell death. However, theoretical studies performed on the molecular level suggest that such nonspecific interactions can also take place with many competitive compounds, such as vitamins containing aromatic rings with lone-pair orbitals. Objective: This work is a theoretical study on the initial Pt-N7(N1) bond formation with vitamins from B group and their comparison with values characterizing native purines. Methods: Geometries of studied structures were optimized with an aid of Gaussian 09 using the B3LYP functional with the 6-31G** basis set. Atomic orbitals of platinum were represented by the lanl2dz basis. Solvation free energies were evaluated by a self-consistent reaction field (SCRF) approach. A dielectric constant of 78 for water was used in the PCM continuum model computations along with radii Bondii. Results: The affinities of mono-aqua cis~[Pt(NH3)2Cl(H2O)]+ and di-aqua cis~ [Pt(NH3)2(H2O)2]2+ derivatives of Cisplatinum toward compounds belonging to the group of eight B vitamins were studied and compared to interactions with canonical purines. All the values of ΔGr unambiguously indicate that reactions with cisPt-diaqua are more preferable, but the comparison of ΔGr values obtained for compounds from vitamin B group and the ones characterizing complexes created by Guanine molecules indicates higher affinity of cisPt monomers toward purines. Conclusion: Based on the observations, the regular intake of vitamin-rich beetroot or carrot juices is strongly discouraged during anticancer therapy using CisPt drug. To confirm the results of the performed computational study, detailed clinical trials should be performed.

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

The stacking interactions of two guanine molecules were analyzed detail at the DF-MP2/aug-cc-pVDZ level of theory for conformations appearing B-DNA. The dependence of intermolecular interaction energies on the pairs of step parameters (shift, slide, rise, tilt, roll and twist) was determined. The values of these parameters were chosen to cover the whole range of variability appearing crystallographic data. The scanning procedure was performed by subsequent changes of two variables with fixed values of the remaining base-pair and base-step BDNA parameters. Additionally, the hybrid variational-perturbational scheme was applied for the decomposition of the interaction energy into physically meaningful contributions at the MP2 level of theory. The significant impact of the mutual orientations of guanine bases was observed not only on the total intermolecular energy but also on its components. The second-order dispersion interaction is the most significant contribution to stabilization energy and is about eight times larger compared to the first-order electrostatic term with relaxation effects, which is also of stabilizing character. The dispersion interactions may vary up to 9.6 kcal mol(-1) between different guanine-guanine conformations. The parameters defining the mutual orientation of stacked guanine molecules have a different impact on the stabilization of the investigated complex. The following base-step parameters have only a minor impact on the stabilization energies: shift-slide, shift-roll, shift-twist, slide-twist and roll-twist. On the other hand, parameters such as rise and tilt significantly influence intermolecular interactions, i.e. strong attraction occurs only for a limited range of their values.

1H and 13C NMR spectra of eleven 2-phenacylbenzoxazoles (ketimine form) show that their CDCl3-solutions contains also (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolimine form). Intramolecular hydrogen bonding in the latter tautomer was found to be significantly weaker than that one in respective (Z)-2-(2-hydroxy-2-phenylvinyl)pyridines. Integrals of the 1H NMR signals were used to evaluate the molar ratio of the tautomers. Strong electron-donating substituents were found to stabilize the ketimine tautomer. pKT (negative logarithm of the equilibrium constant, KT = [ketimine]/[enolimine]) was found to be linearly dependent on the Hammett substituent constant σ. The results of the MP2 ab initio calculations reveal enolimine including an intramolecular OH···N hydrogen bond to be the most stable form both with electron-donor and electron-acceptor substituents. The stability of ketimines is an intermediate of those found for enolimines and enaminones i.e., (E)-2-(benzo[d]oxazol-2(3H)-ylidene)-1-phenylethanones. 13C CPMAS NMR spectral data reveal that in the crystalline state the ketimine tautomer is predominant in p-NMe2 substituted congener. On the other hand, enolimine forms were detected there when the substituent has less electron-donating character or when it is an electron-acceptor by character.

The intermolecular interaction energies in central guanine triad of telomeric B-DNA were estimated based on ab initio quantum chemistry calculations on the MP2/aDZ level of theory. The source of structural information was molecular dynamics simulation of both canonical (AGGGTT) and oxidized (AG8oxoGGTT) telomere units. Our calculations demonstrate that significant stiffness of central triad occurs if 8oxoG is present. The origin of such feature is mainly due to the increase of stacking interactions of 8oxoG with neighbouring guanine molecules and stronger hydrogen bonding formation of 8oxoG with cytosine if compared with canonical guanine. Another interesting observation is the context independence of stacking interactions of 8oxoG. Unlike to 5'-G2/G3-3' and 5'-G3/G4-3' sequences which are energetically different, 5'-G2/8oxoG3-3' and 5'-8oxoG3/G4-3' sequences are almost iso-energetic.