Sonia M. Fiuza

A conformational and vibrational analysis of an antiproliferative spermine-based dinuclear Pd(II) complex (Pd₂-Spm) is reported. Density functional theory coupled to all-electron basis sets was used to perform quantum mechanical calculations aimed at determining the strategy best suited for accurately representing this molecule and achieving an optimal accordance with the experimental data. The structural parameters and the vibrational frequencies predicted by the calculations are compared with the corresponding experimental data. The results support a relationship between the strength of the metal-ligand bonds and the antitumor activity of the compound.

The present study reports a performance evaluation of the new Gaussian program version G09 relatively to the previous one in what concerns the SCRF formalism. The potential improvements achieved by changing program version and other SCRF defining parameters (like radii and SCRF models) were evaluated, by comparing the predicted values of several molecular properties with the corresponding experimental values reported in the literature. The relevance of the dispersion effects in the prediction of those molecular properties was inferred by considering the G09 newly implemented B97D DFT. On the whole, the results showed that the precision achieved in the molecular properties prediction is strongly dependent on the choice of the computation defining parameters. Moreover, direct comparisons between results obtained using either G03 or G09 require precaution.

A conformational analysis of the Pt(dap)Cl₂ complex (dap = 1, 3‐diaminopropane) was performed by vibrational spectroscopy (FTIR, Raman, and INS), coupled to quantum mechanical methods within the density functional theory (DFT) and effective core potential (ECP) approaches. A complete spectral assignment of the system was achieved, due to the combined use of all available vibrational spectroscopic techniques. A good agreement was found between experimental and theoretical results, as well as with reported data for analogous complexes (e.g., cisplatin).

A dinuclear palladium‐based complex (Pd₂‐Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF‐7 and MDA‐MB‐231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd₂‐Spm is more effective against the estrogen receptors [ER(−)] cell line MDA‐MB‐231, while cDDP displayed better results for the ER(+) MCF‐7 cell line. It was shown that, like cDDP, Pd₂‐Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd₂‐Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd₂‐Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd₂‐Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.

The validity of the mPW1PW91 density functional theory (DFT) method coupled to the all‐electron basis set 6‐31G* (mPW1PW/6‐31G*) for the study of amines, using isopropylamine (iPram) as a case study, was evaluated. Validation was performed by comparing the calculated values with the corresponding experimental results obtained and/or reported in the literature. Moreover, the accuracy of that theoretical level was compared with that of other widely used theoretical levels, namely HF/6‐31G*, B3LYP/6‐31G* and MP2/6‐31G*. The effect of basis set improvement within the mPW1PW protocol was evaluated considering the widely used 6‐311G** basis set. On the whole, the results clearly show that the mPW1PW/6‐31G* calculations are a suitable tool for the prediction of the structural and vibrational features of iPram. The validation of the theoretical methodology allowed a complete revision of the vibrational assignments previously reported in the literature, being the result of several proposed re‐assignments. Copyright © 2010 John Wiley & Sons, Ltd.

A conformational and vibrational analysis of cis-diamminedichloropalladium(II) (cDDPd) is reported. Several theoretical methods (from Hartree–Fock to Møller–Plesset and Density Functional Theory) combined with different all-electron basis-sets are evaluated, in view of determining the best suited strategy for accurately representing this molecule. This choice is based on the best compromise between accuracy and computational requirements. Different scaling models were tested for obtaining the best scaling schemes of the vibrational modes to be used in this type of inorganic systems. The structural parameters and vibrational results predicted by the calculations are compared with the corresponding experimental data, namely X-ray structure and vibrational spectra. Finally, a complete assignment of the cDDPd vibrational spectra is presented.

The interaction of double-stranded DNA with two polynuclear Pd(II) chelates with the biogenic polyamines spermidine (Spd) and spermine (Spm), Pd(II)−Spd and Pd(II)−Spm, as well as with the free ligands Spd and Spm, was studied using atomic force microscopy (AFM) at a highly oriented pyrolytic graphite (HOPG) surface, voltammetry at a glassy carbon (GC) electrode, and gel electrophoresis. The AFM and voltammetric results showed that the interaction of Spd and Spm with DNA occurred even for a low concentration of polyamines and caused no oxidative damage to DNA. The Pd(II)−Spd and Pd(II)−Spm complexes were found to induce greater morphological changes in the dsDNA conformation, when compared with their ligands. The interaction was specific, inducing distortion and local denaturation of the B-DNA structure with release of some guanine bases. The DNA strands partially opened give rise to palladium intra- and interstrand cross-links, leading to the formation of DNA adducts and aggregates, particularly in the case of the Pd(II)−Spd complex.