Dynamic nature of the intramolecular electronic coupling mediated by a solvent molecule: a computational study

We present a combined Molecular Dynamics/Quantum Chemical study of the solvent-mediated electronic coupling between an electron donor and acceptor in a C-clamp molecule. We characterize the coupling fluctuations due to the solvent motion for different solvents (acetonitrile, benzene, 1,3-diisopropyl-benzene) for the charge separation and the charge recombination processes. The time scale for solvent-induced coupling fluctuation is approximately 0.1 ps. The effect of these fluctuations on the observed rate is discussed using a recently developed theoretical model. We show that, while the microscopic charge transfer process is very complicated and its computational modeling very subtle, the macroscopic phenomenology can be captured by the standard models. Analyzing the contribution to the coupling given by different solvent orbitals, we find that many solvent orbitals mediate the electron transfer and that paths through different solvent orbitals can interfere constructively or destructively. A relatively small subset of substrate-solvent configurations dominate contributions to solvent-mediated coupling. This subset of configurations is related to the electronic structure of the C-clamp molecule.     

Optimal virtual orbitals to relax wave functions built up with transferred extremely localized molecular orbitals

Extremely localized molecular orbitals (ELMOs), namely orbitals strictly localized on molecular fragments, are easily transferable from one molecule to another one. Hence, they provide a natural way to set up the electronic structure of large molecules using a data base of orbitals obtained from model molecules. However, this procedure obviously increases the energy with respect to a traditional MO calculation. To gain accuracy, it is important to introduce a partial electron delocalization. This can be carried out by defining proper optimal virtual orbitals that supply an efficient set for nonorthogonal configurations to be employed in VB-like expansions.     

High-performance liquid chromatography with post-column derivatisation and fluorescence detection for sensitive determination of aflatoxin M1 in milk and cheese

A new HPLC method with fluorescence detection using pyridinium hydrobromide perbromide as a post-column derivatising agent has been developed to determine aflatoxin M1 in milk and cheese. The detection limits were 1 ng/kg for milk and 5 ng/kg for cheese. The calibration curve was linear from 0.001 to 0.1 ng injected. The method includes a preliminary C18-SPE clean-up and the average recoveries of Aflatoxin M1 from milk and cheese, spiked at levels of 25-75 ng/kg and 100-300 ng/kg, respectively, were 90 and 76%; the precision (RSDr) ranged from 1.7 to 2.6% for milk and from 3.5 to 6.5% for cheese. The method is rapid, easily automatable and therefore useful for accurate and precise screening of aflatoxin M1 in milk and cheese.     

Primate beta-defensins--structure, function and evolution

Host defense peptides (HDPs) are endogenous antibiotics that play a multifunctional role in the innate immunity of mammals. Among these, beta-defensins contribute to mucosal and epithelial defense, also acting as signal molecules for cellular components of innate and adaptive immunity. Numerous members of this family have been identified in mammalian and avian species, and genomic studies in human and mouse indicate a considerable complexity in their gene organization. Recent reports on the evolution of primate and rodent members of this family indicate quite a complex pattern of variation. In this review we briefly discuss the evolution of mammalian beta-defensins in relation to other types of defensins, and then concentrate on the evolution of beta-defensins 1 to 4 in primates. In particular, the surprisingly varied patterns of evolution, which range from neutral or weakly purifying, to positive selection to a high level of conservation are analyzed in terms of possible genetics, structural or functional implications, as well as to observed variations on the antimicrobial activity in vitro. The role of polymorphisms in the genes encoding for these host defense peptides in determining susceptibility to human diseases are also briefly considered.     

Relaxation processes in room temperature ionic liquids: the case of 1-butyl-3-methyl imidazolium hexafluorophosphate

A detailed investigation on the nature of the relaxation processes occurring in a typical room temperature ionic liquid (RTIL), namely, 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim][PF(6)]), is reported. The study was conducted using both elastic and inelastic neutron scattering over a wide temperature range from 10 to 400 K, accessing the dynamic features of both the liquid and glassy amorphous states. In this study, the inelastic fixed energy scan technique has been applied for the first time to this class of materials. Using this technique, the existence of two relaxation processes below the glass transition and a further diffusive process occurring above the glass-liquid transition are observed. The low temperature processes are associated with methyl group rotation and butyl chain relaxation in the glassy state and have been modeled in terms of two Debye-like, Arrhenius activated processes. The high temperature process has been modeled in terms of a Kohlraush-Williams-Watts relaxation, with a distinct Vogel-Fulcher-Tamman temperature dependence. These results provide novel information that will be useful in rationalizing the observed structural and dynamical behavior of RTILs in the amorphous state.     

Traceless solid-phase synthesis of 2,4,6-chlorodiamino and triaminopyrimidines

An effective traceless solid-phase synthesis of chloro-diaminopyrimidines via an amino-de-chlorination reaction of polymer-bound 4-alkoxycarbonylamino-2,6-dichloropyrimidines has been developed. After release from the polymer the target molecules were obtained in good to excellent purity, although with modest regiocontrol. Further reaction of solid-supported N-alkoxycarbonyl-chloro-diaminopyrimidines with secondary amines afforded triaminopyrimidines in good purity under mild conditions, whereas less nucleophilic primary amines did not perform well under the conditions explored so far.     

An approximate expression of the electrostatic molecular potential for benzenic compounds

A method for getting approximate but realistic evaluations of the electrostatic molecular potential for benzene derivatives is presented and discussed. The method is based on a partition of the whole molecular observable into directly transferable contributions, which can be calculated without a previous knowledge of the molecular wavefunction. The algorithm, which probably is applicable also to other aromatic compounds, implements a preceding study concerning only unconjugated molecules.     

A more convenient and general procedure for O-monobenzylation of diols via stannylenes: a critical reevaluation of the Bu2SnO method

A more consistent, straightforward, and economical protocol for generation of stannylene species and their reaction with BnBr leading to products of O-monobenzylation of diols has been set. It has shown to be specially indicated for substrates bearing vicinal trans 1,2-diol moieties on cyclohexane backbones, which are more resistant to these transformations. Such protocol has been successfully applied to myo-inositol derivatives and acyclic diols.     

Synthesis, structure and conformation of partially-modified retro- and retro-inverso psi[NHCH(CF3)]Gly peptides

Partially modified retro- (PMR) and retro-inverso (PMRI) psi[NHCH(CF(3))]Gly peptides, a conceptually new class of peptidomimetics, have been synthesized in wide structural diversity and variable length by aza-Michael reaction of enantiomerically pure alpha-amino esters and peptides with enantiomerically and geometrically pure N-4,4,4-trifluorocrotonoyl-oxazolidin-2-ones. The factors underlying the observed moderate to good diastereocontrol have been investigated. The conformations of model PMR-psi[NHCH(CF(3))]Gly tripeptides have been studied in solution by (1)H NMR spectroscopy supported by MD calculations, as well as in the solid-state by X-ray diffraction. Remarkable stability of turn-like conformations, comparable to that of parent malonyl-based retropeptides, was evidenced, as a likely consequence of two main factors: 1) severe torsional restrictions about sp(3) bonds in the [CO-CH(2)-CH(CF(3))-NH-CH(R)-CO] module, which is biased by the stereoelectronically demanding CF(3) group and the R side chain; 2) formation of nine-membered intramolecularly hydrogen-bonded rings, which have been clearly detected both in CHCl(3) solution and in some crystal structures. The former factor seems to be more important, as turn-like conformations were found in the solid-state even in the absence of intramolecular hydrogen bonding. The relative configuration of the -C*H(CF(3))NHC*H(R)- stereogenic centers has a major effect on the stability of the turn-like conformation, which seems to require a syn stereochemistry. X-ray diffraction and ab initio computational studies showed that the [-CH(CF(3))NH-] group can be seen as a sort of hybrid between a peptide bond mimic and a proteolytic transition state analogue, as it combines some of the properties of a peptidyl -CONH- group (low NH basicity, CH(CF(3))-NH-CH backbone angle close to 120 degrees, C-CF(3) bond substantially isopolar with the C=O) with some others of the tetrahedral intermediate [-C(OX)(O(-))NH-] involved in the protease-mediated hydrolysis reaction of a peptide bond (high electron density on the CF(3) group, tetrahedral backbone carbon).