Biomedical subjects

Wagner B De Almeida

Publications and source records attributed to Wagner B De Almeida.

6 recordsLinked to original sources

PubMed2006

Monte Carlo simulation of cisplatin molecule in aqueous solution.

The Lennard-Jones (12-6) parameters were obtained for all atoms of cisplatin molecule using the ab initio quantum mechanical potential energy surface for the water-cisplatin interaction as reference data. The parameters found were (epsilon/kcal.mol(-1) and sigma/angstroms) 1.0550, 3.6590 (Pt); 0.0381, 4.6272 (Cl); 0.0455, 3.3783 (N); and 0.0185, 0.0936 (H) and provided very good results for the description of the aqueous solution of cisplatin through Monte Carlo simulation. From statistical analysis of solute-solvent interactions, we observed that the NH3 groups are involved in 53% of the calculated hydrogen bonds with a significant contribution from chlorides (41%) and only 6% involving the Pt center. This is in agreement with the expected behavior for such molecules. Two hydration shells with 22 and 81 water molecules, respectively, centered around 4.6 and 7.3 angstroms were found from the center of mass pair correlation function analysis. The cisplatin atomic Lennard-Jones parameters are reported for the first time, and they might be useful for studying the structure, properties, and processes of cisplatin-like molecules in aqueous solution, including explicitly the solvent effect.

Journal Article↗

PubMed2006

Structure and properties of the 5a,6-anhydrotetracycline-platinum(II) dichloride complex: a theoretical ab initio study.

Ab initio structural parameters, relative energies and spectroscopic properties are reported for the 5a,6-anhydrotetracycline-platinum(II) dichloride complex. Distinct coordination modes were analyzed in gas phase and aqueous medium indicating the tricarbonylmethane moiety (O3-Oam-O1) as the most probable Pt(II) complexation sites, supporting experimental proposals. The theoretical (1)H NMR analysis in conjunction with the observed data suggests that the Pt(II) might be bound to the O3-Oam preferentially, even though this site was found slightly unfavorable, based on energetic grounds, relative to O1-Oam. The aquation reaction, which is an important activation step in the action mechanism of cisplatin like molecules, was also investigated showing rate constants (0.5-1 x 10(-5) M(-1) s(-1)) of the same order of magnitude as those for the parent cisplatin compound. This is an important result stressing the importance of tetracyclines-Pt(II) complexes as lead compounds for the development of new platinum based antitumor drugs.

Chlorides↗

PubMed2005

Theoretical study of the alpha-cyclodextrin dimer.

The molecular structure, stabilization energy, and thermodynamic properties of the plausible modes of the interaction for the three possible alpha-cyclodextrin (alpha-CD) dimers (head-to-head, tail-to-tail, and head-to-tail) with a water cluster were obtained using quantum chemical methods for the first time. Nine distinct spatial arrangements were investigated. The head-to-head mode of interaction with water is preferred by more than 10 kcal.mol(-1) (BLYP/6-31G(d,p)//PM3 Gibbs free energy difference value at room temperature) in relation to the next stable structure, with a water dimer structure placed inside each cavity and cyclic water tetramers surrounding each tail end. The inter alpha-CD hydrogen bonds play a major role to stabilize the dimeric structures, with no water tetramer being found between the two alpha-CD subunits for the preferred global minimum structure. Therefore, a theoretical model aimed to describe the behavior of alpha-CD dimer, or their inclusion complexes, in the aqueous media should take into account this preference for binding of the water molecules.

Computer Simulation↗

PubMed2005

Linear free energy relationship for 4-substituted (o-phenylenediamine)platinum(II) dichloride derivatives using quantum mechanical descriptors.

In the present work quantum mechanical methods were used to calculate the rate constants for the first step of the aquation of a set of 4-substituted (o-phenylenediamine)platinum(II) dichloride derivatives containing electron-donating and withdrawing substituents at the 4-position of the aromatic ring. A linear free energy relationship was obtained for log(k(X)/k(H)), k being the rate constant for the first step of hydrolysis, and the electronic Hammett constants sigma(m) and sigma(p). The results showed that electron-donating groups promote the hydrolysis reaction. The quantitative models described here may be useful for the rational design of new, less mutagenic drugs based on platinum complexes.

Antineoplastic Agents↗

PubMed2005

Vibrational spectra of Na, K, Mn2+, Ni2+ and Zn2+ salts of 1,2,4,5-benzenetetracarboxylic (pyromellitic) acid--a short hydrogen bond evidence.

Five salts of 1,2,4,5-benzenetetracarboxylic acid (pyromellitic acid), [C6H2(COO)4H4], have been synthesized and investigated by infrared and Raman spectroscopy and by single crystal X-ray diffraction methods: sodium salt [Na2(H2O)2][C6H2(COO)4H2], potassium salt [K(H2O)3][C6H2(COO)4H3] and transition metal salts [M(H2O)6][C6H2(COO)4H2], which M = Mn, Ni and Zn. Crystal structures of all five compounds show short intramolecular asymmetric hydrogen bonds (SHB) between adjacent carboxyl groups with O...O distance average of 2.40 A. The Raman and infrared spectra reported indicate the presence of short hydrogen bonds in all salts, in agreement with the X-ray data. The O-H stretching mode [nu(OH)] had been observed at about 2500 cm(-1). Deuterated analogues were synthesized and their Raman spectra show that nu(OH)/nu(OD) ratio average is about unit. The symmetric [nu(sym)(O..H..O)] and asymmetric [nu(asym)(O..H..O)] stretching modes have been attributed about 300 and 870 cm(-1), respectively, in all salts, and for deuterated analogues, the ratio nu(OH)/nu(OD) to nu(sym)(O..H..O, O..D..O) is close to unit like it occurs in nu(OH). The vibrational modes, mainly SHB modes, are tentatively assigned by molecular orbital ab initio calculations of pyromellitic acid and anions [C6H2(COO)4H3]- and [C6H2(COO)4H2]2-. Geometry optimizations showed a good agreement with experimental data. Frequency calculation confirms the assignment of specific vibrational modes. Ab initio calculations show that nu(C=O) and nu(sym)(COO) are strongly coupled with in plane OH bending [delta(OH)]. In Raman spectra of deuterated analogues is observed a frequency shift of these bands.

Benzoates↗

PubMed2004

An ab initio correlated study of the potential energy surface for the HOBr.H2O complex.

The potential energy surface (PES) for the HOBr.H(2)O complex has been investigated using second- and fourth-order Møller-Plesset perturbation theory (MP2, MP4) and coupled cluster theory with single and doubles excitations (CCSD), and a perturbative approximation of triple excitations (CCSD-T), correlated ab initio levels of theory employing basis sets of triple zeta quality with polarization and diffuse functions up to the 6-311++G(3dp,3df ) standard Pople's basis set. Six stationary points being three minima, two first-order transition state (TS) structures and one second-order TS were located on the PES. The global minimum syn and the anti equilibrium structure are virtually degenerated [DeltaE(ele-nuc) approximately 0.3 kcal mol(-1), CCSD-T/6-311++G(3df,3pd) value], with the third minima being approximately 4 kcal mol(-1) away. IRC analysis was performed to confirm the correct connectivity of the two first-order TS structures. The CCSD-T/6-311++G(3df,3pd)//MP2/6-311G(d,p) barrier for the syn<-->anti interconversion is 0.3 kcal mol(-1), indicating that a mixture of the syn and anti forms of the HOBr.H(2)O complex is likely to exist.

Journal Article↗