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In this work we studied a ureid system, holding an imine skeleton with an endo (1) or exocyclic (2) double bond. Through a [2 + 2] cycloaddition reaction with ketene it forms β-lactam ring derivatives of spiro (3) or conjugate (4) types. The semi-empirical AM1 method was used to calculate the cycloaddition mechanism. Geometries of the reactants, transition states, intermediates and products were completely optimized and characterized in relation to their minimum or maximum nature on the potential energy surface. The cycloaddition reaction proceeds via non-concerted mechanism with the initial formation of an intermediate with some zwitterionic character. By rotation about the N 1 C 2 bond, this gives a second intermediate which leads to the final product after formation of the C 3 C 4 bond. The second step was found to be rate determining, with an activation energy of 29–33 kcal mol −1 . The reaction involving the endocyclic bond for formation of the conjugate product or the exocyclic bond for formation of the spiro product showed basically the same energy surface, with a slight (1–2 kcal mol −1 ) preference for the spiro product (3).

a Universidade Federal Fluminense, Instituto de Quimica, Departamento de Quimica Orgânica, 24020-141 Niteroi, Rio de Janeiro, Brazil. b Universidade Federal do Rio de Janeiro, Instituto de Quimica, 27930-560, Macae, Rio de Janeiro, Brazil. c Universidade Federal Fluminense, Instituto de Quimica, Departamento de Quimica Inorgânica, 24020-141 Niteroi, Rio de Janeiro, Brazil. d Universidade Federal Fluminense, Faculdade de Farmacia, Departamento de Farmacia e Administracao Farmaceutica, 24241-000, Niteroi, Rio de Janeiro, Brazil.

The mobility and rearrangement of the C4H7(+) system over Chabazite were studied using ab initio molecular dynamics. The results indicated the high mobility of the cations, which can rearrange within picosecond time intervals. Experimental studies of nucleophilic substitution supported the theoretical findings.

Density Functional Theory (UB3LYP/6-311++G(d,p)) calculations of the affinity of the pentaaqua nickel(II) complex for a set of phosphoryl [Oï£P(H)(CH3)(PhR)], imino [HNï£C(CH 3)(PhR)], thiocarbonyl [Sï£C(CH3)(PhR)] and carbonyl [Oï£C(CH3)(PhR)] ligands were performed, where Rï£NH2, OCH3, OH, CH3, H, Cl, CN, and NO2 is a substituent at the para-position of a phenyl ring.The affinity of the pentaaqua nickel(II) complex for these ligands was analized and quantified in terms of interaction enthalpy (ΔH), Gibbs free energy (ΔG298), geometric and electronic parameters of the resultant octahedral complexes. The ΔH and ΔG298 results show that the ligand coordination strength increases in the following order: carbonyl < thiocarbonyl < imino < phosphoryl. This coordination strength order is also observed in the analysis of the metal-ligand distances and charges on the ligand atom that interacts with the Ni(II) cation. The electronic character of the substituent R is the main parameter that affects the strength of the metal-ligand coordination. Ligands containing electron-donating groups (NH 2, OCH3, OH) have more exothermic ΔH and ΔG298 than ligands with electron-withdrawing groups (Cl, CN, NO2). The metal-ligand interaction decomposed by means of the energy decomposition analysis (EDA) method shows that the electronic character of the ligand modulates all the components of the metal-ligand interaction. The absolute softness of the free ligands is correlated with the covalent contribution to the instantaneous interaction energy calculated using the EDA method. © 2013 Wiley Periodicals, Inc. The interactions between metal cations and biomolecules are extensively studied in bioinorganic and coordination chemistry. Transition metal ions are present in many enzymes, metalloproteins, peptide hormones, and nucleic acids and are fundamental for their biological functions. In this work, the affinity of the pentaaqua nickel(II) complex toward a set of para-substituted ligands is evaluated. The electronic nature of the ligand modulates the magnitude of the electrostatic, covalent, and repulsion components of the interaction. © 2013 Wiley Periodicals, Inc.

A detailed theoretical study of the 1,7,1l,17-tetraoxa-2,6,12,16-tetraaza-cycloeicosane ligand ([20]AneN4O4) coordinated to Fe2+, Co2+, Ni2+, Ru2+, Rh2+, and Pd2+ transition metal ions was carried out with the B3LYP method. Two different cases were performed: when nitrogen is the donor atom (1aq) and also with the oxygen as the donor atom (1bq). For all the cases performed in this study 1aq structures were always more stable than the 1bq ones. Considering each row is possible to see that the energy increases with the increase of the atomic number. The M2+ cation binding energies for the 1aq complexes increase with the following order: Fe2+ < Ru2+ < Co2+ < Ni2+ < Rh2+ < Pd2+.

Lawsone (I) is used as starting material for the optimized reductive alkylation process to yield the title compounds including phthiocol (IIa) and lapachol (IIIb).

The CH 49 * potential energy surface (PES) is investigated using level ab initio molecular orbital theory. All structures were fully optimized at Hartree-Fock (HF) and correlated levels (HF/6-31G * , MP2(full)/6-31G * , and MP2-(full)/6-31G ** ) followed by single point energy calculations at MP4sdtq/6-31G ** //MP2(full)/6-31G ** . The C s 1, C 3h 2, and C 3v 3 forms of the tert-butyl cation were investigated

A series of (E) and (Z)-ferrocenyl oxindoles were prepared by coupling substituted oxindoles to ferrocenylcarboxyaldehyde in the presence of morpholine as a catalyst. The redox behavior of these isomers was determined by cyclic voltammetry. The effects of the oxindole derivatives on the migration of human breast cancer cells were evaluated using the wound-healing assay and the Boyden chamber cell-migration assay. The most potent Z isomers 11b (IC(50) = 0.89 microM), 12b (IC(50) = 0.49 microM) and 17b (IC(50) = 0.64 microM) could represent attractive new lead compounds for further development for cancer therapy.

Through-space NMR shieldings were calculated for trinuclear metal-carbonyl compounds [M(3)(CO)(12)] (M = Fe, Ru, Os), employing the nucleus-independent chemical shift approach. The through-space shieldings were visualized as a contour plot of iso-chemical shielding surfaces, and were applied to quantify the overall anisotropic effect of the carbonyl groups, as well as to identify the influence of the transition metal on the scopes of the corresponding anisotropy cones. The shielding surfaces show that the anisotropic effect of the carbonyl groups at equatorial positions changes depending on the metal. This effect was associated with pi-backdonation from the metal to the carbonyl groups in that position, in agreement with geometric data as well as calculated NMR parameters. Therefore, visualization of the through-space NMR shieldings of trinuclear metal-carbonyl compounds of group 8 is able to reflect the distinct arrangements of the carbonyl groups in these organometallic compounds.

Artemisinin is a sesquiterpene lactone with an endoperoxide function that is currently being used against strains of Plasmodium falciparum. Endoperoxides are supposed to act on heme leading to reduction of the peroxide bond and production of radicals that can kill the parasite. As artemisinin, other natural compounds have the peroxide group and may also show antimalarial activity. This fact motivated us to study the interaction of 18 peroxides natural Brazilian flora with the heme group and compared with the values obtained for artemisinin. Initially, a conformational search was performed using the MM3 method for each molecule. The most stable conformers were optimized by the PM3(tm) method. Then, there was a docking between the peroxide and the heme group, again followed by a conformational search. Finally, the complex was optimized to obtain highest occupied molecular orbital, lowest unoccupied molecular orbital, and molecular electrostatic potential (MEP) by the PM3(tm) method. All these calculations were performed using the Titan package. Among the natural peroxides, we studied (18), four have molecular orbital, MEP, and interaction energies similar to artemisinin. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

The closely related C s (1) and C 2v (3) structures of CH 5 + have been reinvestigated at many ab initio levels using MP2/6-31G .. and MP2/6-311++G(2df,2pd) geometries. The largest basis sets employed were 6-311 (3df,2p), 6-311++G(3df,3pd), and the Dunning «correlation consistent» polarized triple-split valence basis set (cc-pVTZ). Electron correlation was probed at the MP4 level, but the QCISD method was also used with the largest basis sets

A statistical model, built using the CODESSA software package, was developed to describe the relationship between the structure of nostoclide derivatives and their ability to interfere with the electron transport chain in the Hill reaction.A QSAR treatment was carried out on a series of compounds designed using the naturally occurring toxin nostoclides to correlate molecular descriptors with their in vitro biological activity (the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplast thylakoid membranes). The treatment using the CODESSA software package resulted in a three-parameter model with n = 19, R(2) = 0.83, F = 23.8 and R(2) (cv) = 0.72. In the proposed model, the Image of Onsager Kirkwood solvation energy, which gives a measure of the polarity of a given compound, is the most important descriptor. The model was internally validated.The results obtained in this study indicate that polarity, as expressed by the dipole moment, is the most relevant molecular property determining efficiency of photosynthetic inhibitory activity.

Short stereoselective syntheses of both 5-substituted-4-amino-pyrrolidin-2-ones and 5-substituted-4-amino-3-pyrrolin-2-ones from natural α-amino acids are described.

Semi-empirical (AM1 and PM3) and DFT (B3LYP/6-31G(d)) calculations were employed to study the tautomeric equilibrium between the aminequinone A and hydroxylquinoneimine B forms of 4-(4-R-phenylamino)naphthalene-1,2-diones. Substituent effects on the tautomeric equilibrium as well as on geometric and electronic parameters were also determined. In the gas phase the hydroxylquinoneimine B form is the most stable, whereas in water the aminequinone A form becomes more stable. The substituents do not modify the relative energies of the two tautomers. These results are in accordance with experimental data reported in the literature.

Charge distributions in half-cage inside and outside isomer alcohols were obtained by STO-3G ab initio calculations. Input optimized geometries were calculated by MM2 and MNDO methods. The MM2 geometry accompanied neutron-diffraction data on relative bond lengths more closely, but this fact had little influence on charge distributions. In C-H bonds under strong non-bonded pressure the electron density maximum of the hydrogen atom is shifted toward the bound carbon resulting in a significant increase in population and relative p character. In such cases, the influence of steric compression may be comparable to that of bond angles in determining hybridization.

Malaria is an infectious disease caused by the unicellular parasite Plasmodium sp. Currently, the malaria parasite is becoming resistant to the traditional pharmacological alternatives, which are ineffective. Artemisinin is the most recent advance in the chemotherapy of malaria. Since it has been proven that artemisinin may act on intracellular heme, we have undertaken a systematic study of several interactions and arrangements between artemisinin and heme. Density Functional Theory calculations were employed to calculate interaction energies, electronic states, and geometrical arrangements for the complex between the heme group and artemisinin. The results show that the interaction between the heme group and artemisinin at long distances occurs through a complex where the iron atom of the heme group retains its electronic features, leading to a quintet state as the most stable one. However, for interaction at short distances, due to artemisinin reduction by the heme group, the most stable complex has a septet spin state. These results suggest that a thermodynamically favorable interaction between artemisinin and heme may happen.

Artemisinin is a sesquiterpene lactone with an endoperoxide function that is essential for its antimalarial activity. The DFT B3LYP method, together with the 6-31G(d) and 6-31+G(d,p) basis set, is employed to calculate a set of radical anions and neutral species supposed to be formed during the rearrangement of artemisinin from the two radicals (C-centered and O-centered) that are supposed to play a relevant role in the mechanism of action. The B3LYP results show that the primary and the secondary radicals centered on C 4 , generated by homolytic break of the C 3 –C 4 bond and by 1,5 hydrogen shift, respectively, are more stable than radicals centered on oxygen. The calculations show that the activation barriers for rearrangements are low, leading to a thermodynamically favorable process. These results reinforce our previous conclusions based on semi-empirical calculations but also give additional information on the reductive decomposition of artemisinin.

Several molecular parameters for 2,3,5-substituted 1,4-naphthoquinones including 2-aziridinyl and 2,3-aziridinyl-1,4-naphthoquinones with antimalarial activities were obtained with the semi-empirical PM3 method. The descriptor related to the Gibbs free energy of an isodesmic equation defining the reduction of the naphthoquinones was found to have high correlation with activity. The quantitative models reported clearly show a dependence of activity on the redox potential for reduction of the naphthoquinones. Compounds with lower values of DeltaG for reduction are more active than those with higher values of DeltaG.

A strong metal support interaction (SMSI) effect was observed on Pd/Nb2O5 and Pd/TiO2 catalysts, and it produces small, exposed Pd ensembles. A decrease in the trans/cis 2-butene ratio was observed after reduction at 773 K. Selectivity changes were ascribed to the decoration model. Theoretical models were developed based on semi-empirical molecular-orbital calculations for 1,3-butadiene and Pd n clusters. Experimental results are in agreement with our theoretical model, which proposes a greater stabilization of the cisoid intermediate on small Pd ensembles.

Four tetrahydropyridocarbazole derivatives were analysed by different mass spectrometry techniques: electrospray ionization, fast atom bombardment and by low and high resolution 70 eV electron ionization. Retro Diels Alder is the main fragmentation pathway, whereas other pathways leading to [M—1]+, [M—CH3]+and double charge ions also occur to considerable extents. Semi-empirical calculation provided some evidence on the nature of tropylium ions [M—1]+. Calculation of ΔHf0indicated that [M+—1] could be formed preferentially when a hydrogen atom is lost from the methyl substituent of the homoaromatic ring.

«Freezing-in» as norcaradiene valence tautomer is possible in the case of 1,6-methanol [10] annulene not only by acceptor substituents on the methylene carbon atom but also by suitable peri-bridges

A computational interface, using sybyl format as an input file, was created in order to calculate connectivity indexes. After generation and classification of all substructures, which derive from the molecular structure, this interface calculates all possible orders from zero up to the maximun number of bonds in the molecule. Other topological indexes such as Wiener and Schultz indexes can also be calculated.

Two series of flexible dicyanomethylene compounds, specifically, class 1 and class 2 compounds, have been designed and synthesised. In class 1 compounds, the dicyanomethylene groups are separated by glycol chain spacers of different lengths, whereas, in class 2 compounds, the spacers are alkyl linkers of different lengths. The notion underlying the design of these compounds is that in class 1 molecules, the spacers contain donor oxygen atoms that could not only form hydrogen bonds during the course of crystal packing but also promote withdrawing effects that modify the photophysical and electrochemical properties of these molecules in solution; in contrast, these effects would be absent for class 2 molecules. However, this study revealed that, with respect to crystal packing, the size of the spacers and their even and odd numbers of atoms are more important than their chemical nature. All of the synthesised compounds exhibited blue emission in the solid state and in CH2Cl2 solutions. The photophysical and electrochemical properties of these compounds in solution were not significantly affected by the type and length of the spacer that was used in each molecule. In the solid state, however, the compound with the shortest spacer showed the highest Stokes shift. The electronic transitions for the synthesized compounds in solution were explained by density functional theory and time-dependent density functional theory calculations, which indicated that the methylene moieties control the properties of both classes of compounds and that the spacers do not conjugate with the end groups. These two series of flexible dicyanomethylene compounds could be utilised as molecular building blocks for the development of new solids with novel properties.

The novel chain compound [Cu(Phtfac)(2)(NITpPy)](n) (where NITpPy = 4-pyridyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and Phtfac = 4,4,4-trifluoro-1-phenylbutane-1,3-dione) was synthesized and characterized structurally, magnetically and by EPR. The compound contains two non equivalent Cu(II) ions, Cu1 and Cu2, located at inversion centers and bridged by a NITpPy ligand coordinating Cu1 through the pyridine donor atom, and Cu2 through a N-O group, resulting in a head-to-head chain structure. The chain exhibits an unusual spin topology with two alternating pairs of magnetic coupling constants. The magnetic behavior was modeled considering a 16-membered ring with alternating exchange couplings. The best fit parameters indicate a ferromagnetic (J(1) = 29.4 cm(-1)), and antiferromagnetic (J(2) = -4.6 cm(-1)) couplings and an average g = 2.05, corresponding to a ground state with three parallel and one anti-parallel spin for each Cu(2)NITpPy(2) unit. DFT calculations allowed assigning the ferromagnetic coupling to Cu-O-NITpPy and the antiferromagnetic coupling to Cu-N(Py)-NITpPy. Single crystal EPR spectra display only one resonance for most field orientations, as a consequence of the collapse of the signals of the different spins produced by the exchange interactions. The observed g-tensor of this resonance is related to those expected for the Cu(II) and radical ions. Comparison of this compound with other Cu-NIT radicals chains bearing different substituents in the organic radicals, highlights that the beta-diketonate ligand plays an important role in determining the final architecture. Moreover, we show how a knowledge of the spin density distribution in the initial building blocks is essential to rationalize the magnetic behavior of the resulting product.

Nesta tese, foram estudadas as reações de troca de ligante cloreto em solução aquosa de complexos que possuem alguma importância biológica. Os complexos escolhidos foram [Ru(NH3)5(Cl)]2+ e trans-[Ru(NH3)4(Py)(Cl)]2+. Cálculos utilizando a Teoria do Funcional de Densidade, mediante a aproximação híbrida QM/EFP, foram realizados para estimar as propriedades estruturais, eletrônicas e energéticas das espécies reagentes, estado de transição e produto ao longo da curva de energia. Estudos da coordenação dos complexos [Ru(NH3)5(H2O)]2+ e trans-[Ru(NH3)4(Py)( H2O)]2+ ao DNA foram realizados para obter o sítio de coordenação preferencial, N3 ou N7, das nucleobases de adenina e guanina. Utilizando nível de teoria DFT e MP2 estimou-se a formação dos adutos de Ru(II)-DNA, [Ru(NH3)4(Nucleobase)(L)]2+ para L= NH3 e L=Py. Usamos também a DFT para investigar a estrutura, a natureza da ligação M(II)- NO e o espectro eletrônico dos complexos [M(imidazol)(PPIX)(L)]q, com M= Fe2+ e Ru2+ e L=NO+, NO e NO-, onde todas as possibilidades de coordenação (.1-N, .1-O e .2-ON) foram utilizadas. Para o estudo da natureza da ligação usamos a Análise de Decomposição de Cargas (CDA) e a Análise da Decomposição da Energia. Utilizamos TD-DFT com o funcional TPSSh para realizar os estudos espectroscópicos dos complexos de [Ru(imidazol)(PPIX)(NO)] e [Ru(imidazol)(PPIX)(NO+)]+. In this thesis, we studied the ligand exchange reactions in aqueous chloride complexes that have some biological importance. The were chosen [Ru(NH3)5(Cl)]2+ e trans-[Ru(NH3)4(Py)(Cl)]2+ complexes. Calculations using the Density Functional Theory, by approximating hybrid QM / EFP, were performed to estimate the structural, electronic and energy properties of the reacting species, product and transition state along the potential energy curve. Studies of the coordination of Ru(NH3)5(H2O)]2+ and trans-[Ru(NH3)4(Py)(H2O)]2+ to DNA were performed to obtain the preferred coordination site, N3 or N7, to the adenine or guanine nucleobases. Using level of theory DFT and MP2 estimated the formation of adducts of Ru(II)-DNA, [Ru(NH3)4(Nucleobase)(L)]2+ for L= NH3 and L=Py. We also used the DFT for investigating the structure, the nature of the binding M(II)-NO and electronic spectra of the complexes M(imidazol)(PPIX)(L)]q, with M=Fe2+ and Ru2+ and L=NO+, NO e NO-, where all the possibilities for coordination (1-N, 1-O and 2-ON) were used. To study the nature of the binding we use the Charge Decomposition Analysis (CDA) and the Energy Decomposition Analysis (EDA). We use TD-DFT with the functional TPSSh to perform spectroscopic studies of complexes [Ru(imidazole)(PPIX)(NO)] and [Ru(imidazole)(PPIX)(NO+)].