Energy decomposition in molecular complexes: implications for the treatment of polarization in molecular simulations

This study examines the contribution of electrostatic and polarization to the interaction energy in a variety of molecular complexes. The results obtained from the Kitaura-Morokuma (KM) energy decomposition analysis at the HF/6-31G(d) level indicate that, for intermolecular distances around the equilibrium geometries, the polarization energy can be determined as the addition of the polarization energies of interacting blocks, as the mixed polarization term is typically negligible. Comparison of KM and QM/MM results shows that the electrostatic energy determined in the KM method is underestimated (in absolute value) by QM/MM methods. The reason of such underestimation can be attributed to the simplified representation of treating the interaction between overlapping charge distribution by the interaction of a QM molecule with a set of point charges. Nevertheless, the polarization energies calculated by KM and QM/MM methods are in close agreement. Finally, a consistent, automated strategy to derive charge distributions that include implicitly polarization effects in pairwise, additive force fields is presented. The strategy relies in the simultaneous fitting of electrostatic and polarization energies computed by placing a suitable perturbing particle at selected points around the molecule. The suitability of these charges to describe molecular interactions is discussed.     

Palladium-catalyzed cascade reaction of alpha,beta-unsaturated sulfones with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions (Pd(OAc)(2) as catalyst, Ag(2)CO(3) as base in DMF at 120 (0)C) takes place mainly by a cascade process, involving one unit of the alkene and three units of the aryl iodide, to afford a substituted 9-phenylsulfonyl-9,10-dihydrophenanthrene. The dominant formation of this 3:1 coupling product, instead of the Heck trisubstituted olefin, shows that aromatic C-H bond activation processes can compete with the usually fast syn beta-hydrogen elimination step in the Heck arylation of an acyclic olefin. The structural scope of this palladium-catalyzed cascade arylation of alpha,beta-unsaturated sulfones has proved to be wide with regard to substitution at the beta-position (alkyl, aryl, or alkenyl substitution), substitution at the sulfone unit (alkyl or phenyl sulfones), and configuration at the CdoublebondC bond (trans or cis). Moreover, although less favored than in the case of the arylation of alpha,beta-unsaturated sulfones, similarly substituted 9,10-dihydrophenanthrenes have also been obtained in the case of alpha,beta-unsaturated phosphine oxides and alpha,beta-unsaturated phosphonate esters. A Pd(0)-Pd(II)-Pd(IV) mechanistic pathway involving the successive formation of highly electrophilic sigma-alkylpalladium intermediates and palladacycles is proposed for this multicomponent arylation.     

Preorganization and reorganization as related factors in enzyme catalysis: the chorismate mutase case

In this paper a deeper insight into the chorismate-to prephenate-rearrangement, catalyzed by Bacillus subtilis chorismate mutase, is provided by means of a combination of statistical quantum mechanics/molecular mechanics simulation methods and hybrid potential energy surface exploration techniques. The main aim of this work is to present an estimation of the preorganization and reorganization terms of the enzyme catalytic rate enhancement. To analyze the first of these, we have studied different conformational equilibria of chorismate in aqueous solution and in the enzyme active site. Our conclusion is that chorismate mutase preferentially binds the reactive conformer of the substrate--that presenting a structure similar to the transition state of the reaction to be catalyzed--with shorter distances between the carbon atoms to be bonded and more diaxial character. With respect to the reorganization effect, an energy decomposition analysis of the potential energies of the reactive reactant and of the reaction transition state in aqueous solution and in the enzyme shows that the enzyme structure is better adapted to the transition structure. This means not only a more negative electrostatic interaction energy with the transition state but also a low enzyme deformation contribution to the energy barrier. Our calculations reveal that the structure of the enzyme is responsible for stabilizing the transition state structure of the reaction, with concomitant selection of the reactive form of the reactants. This is, the same enzymatic pattern that stabilizes the transition structure also promotes those reactant structures closer to the transition structure (i.e., the reactive reactants). In fact, both reorganization and preorganization effects have to be considered as the two faces of the same coin, having a common origin in the effect of the enzyme structure on the energy surface of the substrate.     

Oligostilbentes from Vitis DavidII

PreviousinvestigationsrevealedthatsomeVitisspeciesarerichinoligostilbenes'-'.InthecontinuinginvestigationforoligostilbenesfromVitisspp-,wehaveisolatedanoveltetrastilbene,davidolA1,alongwithresveratrol',( )-E-viniferin',ampelopsinC',ampelopsinE',vitisinAl'3andhopeaphenol7-9fromthestemsofVitisdavidiiFoex9.ThedriedpowderedstemsofVdavidiiFoex.wasextractedwithacetone.TheacetoneextractwasthenconcentratedunderreducedpressureandfractionatedbyaseriesofsolventpartitionintoanEtOAc-solublephenolicfr…     

Effect of ionic strength on the formal potential of the glass electrode in various saline media

We examined the variation with ionic strength (I, adjusted with KCl, KNO₃, KBr, NaCl or NaClO₄) of the formal potential (E_const) for glass electrodes exhibiting a Nernstian response (i.e. E_cell=E_const−s log [H⁺]). For this purpose, we investigated the different factors included in the formal potential, so we obtained reported values for the liquid junction potential as a function of ionic strength and determined the logarithm of the activity coefficient for the proton in various saline media, using Pitzer equations.     

Preparation of new monoanionic "scorpionate" ligands: synthesis and structural characterization of titanium(IV) complexes bearing this class of ligand

The preparation of new "scorpionate" ligands in the form of the lithium derivatives [(Li(bdmpzdta)(H(2)O))(4)] (1) [bdmpzdta = bis(3,5-dimethylpyrazol-1-yl)dithioacetate], [Li(bdphpza)(H(2)O)(THF)] (2) [bdphpza = bis(3,5-diphenylpyrazol-1-yl)acetate], and [Li(bdphpzdta)(H(2)O)(THF)] (3) [bdphpzdta = bis(3,5-diphenylpyrazol-1-yl)dithioacetate] has been carried out. Furthermore, a series of titanium complexes has been prepared by reaction of TiCl(4)(THF)(2) with the lithium reagents [(Li(bdmpza)(H(2)O))(4)] (4) [bdmpza = bis(3,5-dimethylpyrazol-1-yl)acetate] and 1. Under the appropriate experimental conditions neutral complexes, namely [TiCl(3)(kappa(3)-bdmpza)] (5), [TiCl(3)(kappa(3)-bdmpzdta)] (6), and [TiCl(2)(kappa(2)-bdmpzdta)(2)] (7), and cationic complexes, namely [TiCl(2)(THF)(kappa(3)-bdmpza)]Cl (8) and [TiCl(2)(THF)(kappa(3)-bdmpzdta)]Cl (9), were isolated. Complexes 8 and 9 undergo an interesting nucleophilic THF ring-opening reaction to give the corresponding alkoxide-containing species [TiCl(2)(kappa(3)-bdmpza)(O(CH(2))(4)Cl)] (10) and [TiCl(2)(kappa(3)-bdmpzdta)(O(CH(2))(4)Cl)] (11). A family of alkoxide-containing complexes of general formulas [TiCl(2)(kappa(3)-bdmpza)(OR)] [R = Me (12); R = Et (14); R = (i)Pr (16); R = (t)Bu (18)] and [TiCl(2)(kappa(3)-bdmpzdta)(OR)] [R = Me (13); R = Et (15); R = (i)Pr (17)] was also prepared. The structures of these complexes have been determined by spectroscopic methods, and in addition, the X-ray crystal structures of 3, 7, 10, and 11 were also established.     

First enantioselective total synthesis of (-)-Centrolobine

[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.     

Comparison of solid-phase extraction methods for the determination of azaspiracids in shellfish by liquid chromatography-electrospray mass spectrometry

Azaspiracids have been identified as the cause of a new toxic syndrome called azaspiracid poisoning (AZP) that has led to incidents of human intoxications throughout Europe following the consumption of mussels. Although five AZP toxins have been structurally elucidated to-date, azaspiracid (AZA1), 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3) are the predominant toxins. Separation of the three main AZP toxins was achieved using reversed-phase liquid chromatography (LC) and coupled to an electrospray ionisation source of an ion-trap mass spectrometer. Five reversed-phase (C18) and three diol solid-phase extraction (SPE) cartridges were compared for their efficacy in the cleanup of shellfish matrix. The comparison was based on the optimum recoveries of AZA1, AZA2 and AZA3 from extracts of mussel tissues. LC-electrospray MS3 analysis was used to quantify the AZP toxins in wash and eluate fractions in the SPE studies. Good recovery and reproducibility data were obtained for one diol SPE cartridge and two C18 SPE cartridge types.