José Walkimar de M. Carneiro

Synthesis of Photosynthesis-Inhibiting Nostoclide Analogues

A series of 34 3-benzyl-5-(arylmethylene)furan-2(5H)-ones, designed using the naturally occurring toxins nostoclides as a lead structure, was synthesized as potential inhibitors of the photosynthetic electron transport. All compounds were fully characterized by IR, NMR (1H and 13C), and MS spectrometry. HMBC and HSQC bidimensional experiments allowed 13C and 1H assignments. Their biological activities were evaluated in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. About two-thirds of the compounds exhibited inhibitory properties in the micromolar range against the basal electron flow from water to K3[Fe(CN)6]. The inhibitory potential of these 3-benzyl-5-(arylmethylene)furan-2(5H)-one lactones is higher than that of other nostoclide analogues previously synthesized in the same laboratories.

Synthesis of rubrolide analogues as new inhibitors of the photosynthetic electron transport chain.

Many natural products have been used as a model for the development of new drugs and agrochemicals. Following this strategy 11 rubrolide analogues, bearing electron-withdrawing and -donating groups at both benzene rings, were prepared starting from commercially available mucobromic acid. The ability of all compounds to inhibit the photosynthetic electron transport chain in the chloroplast was investigated. The rubrolide analogues were effective in interfering with the light-driven ferricyanide reduction by isolated chloroplasts. The IC(50) values of the most active derivatives are in fact only 1 order of magnitude higher than those of commercial herbicides sharing the same mode of action, such as Diuron (0.27 μM). QSAR studies indicate that the most efficient compounds are those having higher ability to accept electrons, either by a reduction process or by an electrophilic reaction mechanism. The results obtained suggest that the rubrolide analogues represent promising candidates for the development of new active principles targeting photosynthesis to be used as herbicides.

Density functional theory study of the adsorption of formaldehyde on Pd4 and on Pd4/gamma-Al2O3 clusters.

B3LYP/LANL2DZ and B3LYP/6-31G(d)-restricted and -unrestricted calculations are employed to calculate energies and adsorption forms of formaldehyde adsorbed on planar and on tetrahedral Pd4 clusters and on a Pd4 cluster supported on Al10O15. Formaldehyde adsorbs on planar Pd4 in the eta(2)(C,O)-di-sigma adsorption mode, while on tetrahedral Pd4, it adsorbs in the eta(2)(C,O)-pi adsorption mode. The adsorption energy on planar Pd4 is -21.4 kcal x mol(-1), whereas for the tetrahedral Pd4 cluster, the adsorption energy is -13.2 kcal x mol(-1). The latter value is close to experimental findings (-12 to -14 kcal x mol(-1)). Adsorption of formaldehyde on Pd4 supported on an Al10O15 cluster leads essentially to the same result as that found for adsorption on the tetrahedral Pd4 cluster. Charge density analysis for the interaction between formaldehyde and the Pd4 clusters indicates strong backdonation in the eta(2) adsorption mode, leading to positive charge on the Pd4 cluster. NBO analysis shows that the highly coordinated octahedral aluminum atoms of Al10O15 donate electron density to the supported Pd4 cluster, while tetrahedral aluminum atoms with lower coordination number have acidic nature and therefore act as electron acceptors.

New copper(II)-radical one dimensional chain: Synthesis, crystal structure, EPR, magnetic properties and DFT calculations

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.

Interaction between alkaline earth cations and oxo-ligands. DFT study of the affinity of the Ca2+ cation for carbonyl ligands

AbstractThe affinity of the Ca2+ ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods. Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)2] (R=H, F, Cl, Br, OH, OCH3, CH3, CN, NH2 and NO2), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca2+ cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less negative (destabilizing the complex formed). FigureThe affinity of Ca2+ for carbonyl ligands is determined by the electronic nature of the substituent. Electron donor substituents bind more strongly than electron acceptor substituents.

A quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity against tumor cells

The semi‐empirical molecular orbital method PM6 was employed to calculate a set of molecular descriptors of 20 sesquiterpene lactones (SQLs) with cytotoxicity against HL‐60 (leukemia) tumor cells. The principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were used to obtain possible relationships between the calculated descriptors and the biological activity of the lactones. Four descriptors were identified as responsible for the separation between the active and inactive compounds: EHOMO (highest occupied molecular orbital energy); Q11 (net atomic charge on C11); Q12 (net atomic charge on C12) and Q13 (net atomic charge on C13). These results indicated that the presence of the α‐methylene‐γ‐lactone group has a significant role in the mechanism by which SQLs exert their biological activities.In order to deepen our knowledge about the structure–activity relationship of sesquiterpene lactones (SQLs), a quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity was performed against HL‐60 (leukemia) tumor cells. The analysis of the molecular descriptors identified as responsible for the separation between the active and inactive compounds indicated that the presence of the α‐methylene‐γ‐lactone functionality has a significant role in the mechanism by which SQLs exert their biological activities. Copyright

Synthesis, electrochemical studies and anticancer activity of ferrocenyl oxindoles

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.

Ab initio charge distributions in half-cage compounds

Abstract 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.

Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg2+ cation for phosphoryl ligands

DFT (B3LYP/6-31+G(d)) calculations of Mg2+ affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)3] (R = H, F, Cl, Br, OH, OCH3, CH3, CN, NH2 and NO2), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg2+ cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H2O)6]2+ complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

Aminequinone-hydroxylquinoneimine tautomeric equilibrium revisited: molecular modeling study of the tautomeric equilibrium and substituent effects in 4-(4-R-phenylamino)naphthalene-1,2-diones.

AbstractSemi-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. FigureThe hydroxylquinoneimine form B1 is the most stable tautomer in the gas-phase. In a polar solvent the aminequinone form A1 becomes the most stable. Substituents have only marginal influence on the relative stabilities of the two tautomers