A new set of basis functions for the discrete geometric approach

By exploiting the geometric structure behind Maxwell’s equations, the so called discrete geometric approach allows to translate the physical laws of electromagnetism into discrete relations, involving circulations and fluxes associated with the geometric elements of a pair of interlocked grids: the primal grid and the dual grid.     

Many-body calculations of molecular electric polarizabilities in asymptotically complete basis sets

The static dipole polarizabilities of Ne, CO, N₂, F₂, HF, H₂O, HCN, and C₂H₂ (acetylene) have been determined close to the Full-CI limit along with an asymptotically complete basis set (CBS), according to the principles of a Focal Point Analysis. For this purpose the results of Finite Field calculations up to the level of Coupled Cluster theory including Single, Double, Triple, Quadruple and perturbative Pentuple excitations [CCSDTQ(P)] were used, in conjunction with suited extrapolations of energies obtained using augmented and doubly-augmented Dunning's correlation consistent polarized valence basis sets of improving quality. The polarizability characteristics of C₂H₄ (ethylene) and C₂H₆ (ethane) have been determined on the same grounds at the CCSDTQ level in the CBS limit. Comparison is made with results obtained using lower levels in electronic correlation, or taking into account the relaxation of the molecular structure due to an adiabatic polarization process. Vibrational corrections to electronic polarizabilities have been empirically estimated according to Born–Oppenheimer Molecular Dynamical simulations employing Density Functional Theory. Confrontation with experiment ultimately indicates relative accuracies of the order of 1 to 2%.     

Identifying conformational changes of the β2 adrenoceptor that enable accurate prediction of ligand/receptor interactions and screening for GPCR modulators

The new β₂ Adrenoceptor (β₂AR) crystal structures provide a high-resolution snapshot of receptor interactions with two particular partial inverse agonists, (−)-carazolol and timolol. However, both experimental and computational studies of GPCR structure are significantly complicated by the existence of multiple conformational states coupled to ligand type and receptor activity. Agonists and antagonists induce or stabilize distinct changes in receptor structure that mediate a range of pharmacological activities. In this work, we (1) established that the existing β₂AR crystallographic conformers can be extended to describe ligand/receptor interactions for additional antagonist types, (2) generated agonist-bound receptor conformations, and (3) validated these models for agonist and antagonist virtual ligand screening (VLS). Using a ligand directed refinement protocol, we derived a single agonist-bound receptor conformation that selectively retrieved a diverse set of full and partial β₂AR agonists in VLS trials. Additionally, the impact of extracellular loop two conformation on VLS was assessed by docking studies with rhodopsin-based β₂AR homology models, and loop-deleted receptor models. A general strategy for constructing and selecting agonist-bound receptor pocket conformations is presented, which may prove broadly useful in creating agonist and antagonist bound models for other GPCRs. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Improved analyte detectability of proteins and peptide lysates by means of multiple large‐volume injection in LC‐MS

A ‘multiple (trapping) large‐volume injection’ approach was developed for the analysis of peptides and proteins. In this way, a maximally 10‐fold gain in sensitivity could be achieved. The system involves the use of an automated 10‐port switching valve in combination with a 1 mm i.d. trapping/guard column and a 1 mm i.d.×150 mm analytical column. The optimized multiple injection/loading procedure allows quantitative measurements of peptides and protein lysates. Linear calibration curves (R² ? 0.988) over a minimum of two orders of magnitude were generated for a range of peptide and protein standards with sensitivities equal to or even exceeding, those generally achieved only through increasing miniaturization (quantification limit ?0.5 pmol/mL).     

Solution enthalpies of hydroxylic compounds

Solution enthalpies of adamantan-1-ol, 2-methyl- butan-2-ol, and 3-methylbutan-1-ol have been measured at 298.15 K, in a set of 16 protogenic and non-protogenic solvents. The identification and quantification of solvent effects on the solution processes under study were performed using quantitative-structure property relationships. The results are discussed in terms of solute–solvent–solvent interactions and also in terms of the influence of compound’s size and position of its hydroxyl group.     

Ligand-accelerated Pd-catalyzed ketone γ-arylation via C-C cleavage with aryl chlorides

A highly efficient Pd-catalyzed arylative ring expansion of cyclobutanols via C-C bond cleavage is presented. The method allows the coupling of aryl chlorides at low catalyst loadings with a wide range of functional groups and substitution patterns, thus constituting a straightforward alternative for preparing rather elusive γ-arylated ketones.