Solvent polarity effects on thermochemical and NMR parameters of spilanthol pharmacological agent: an experimental and DFT investigation

Structural Chemistry - Through experimental and appropriate quantum chemical approaches, we perform a systematic investigation of the solvent effects on thermochemical and nuclear magnetic...     

Diffusion in stochastic sandpiles

We study diffusion of particles in large-scale simulations of one-dimensional stochastic sandpiles, in both the restricted and unrestricted versions. The results indicate that the diffusion constant scales in the same manner as the activity density, so that it represents an alternative definition of an order parameter. The critical behavior of the unrestricted sandpile is very similar to that of its restricted counterpart, including the fact that a data collapse of the order parameter as a function of the particle density is possible, but with a narrow scaling region. We also develop a series expansion, in inverse powers of the density, for the collective diffusion coefficient in a variant of the stochastic sandpile in which the toppling rate at a site with n particles is n(n-1), and compare the theoretical prediction with simulation results.     

Phospho‐l‐tyrosine‐agarose chromatography: Adsorption of human IgG and its proteolytic fragments

The behavior of human immunoglobulin G (IgG) and antigen‐binding fragment (Fab fragment) adsorption onto phospho‐l ‐tyrosine immobilized on agarose (P‐Tyr‐agarose) was evaluated by pseudoaffinity chromatography. The effects of buffer systems MES, MOPS, Bis–Tris, Tris–HCl and sodium phosphate (NaP) and pH on IgG adsorption were studied and high purity values were obtained (96%, based on ELISA analysis of albumin, transferrin and immunoglobulins A, G and M) when IgG was purified from human plasma diluted in 10 mmol L^?1 NaP buffer at pH 6.0. The capture of IgG by the P‐Tyr‐agarose was also promising, since 91% of the IgG was adsorbed when plasma was diluted in 25 mmol L^?1 MES buffer at pH 5.5, recommending its use for IgG depletion from human plasma under this condition. The experimental data on IgG adsorption kinetics were in agreement with the pseudo‐second‐order model. The adsorption isotherm data were well described by the Langmuir–Freundlich model with the value of parameter n being <1 (0.72), indicating negative cooperativity. Selectivity was achieved on P‐Tyr‐agarose from digested human IgG in HEPES 25 mmol L^?1 buffer at pH 7.0 where Fab fragments were obtained in eluted fractions without Fc fragments (but with uncleaved IgG) with 86.2% recovery.     

Towards the Accurate Thermodynamic Characterization of Enzyme Reaction Mechanisms

We employed QM/MM molecular dynamics (MD) simulations to characterize the rate-limiting step of the glycosylation reaction of pancreatic α-amylase with combined DFT/molecular dynamics methods (PBE/def2-SVP : AMBER). Upon careful choice of four starting active site conformations based on thorough reactivity criteria, Gibbs energy profiles were calculated with umbrella sampling simulations within a statistical convergence of 1–2 kcal ⋅ mol⁻¹. Nevertheless, Gibbs activation barriers and reaction energies still varied from 11.0 to 16.8 kcal ⋅ mol⁻¹ and −6.3 to +3.8 kcal ⋅ mol⁻¹ depending on the starting conformations, showing that despite significant state-of-the-art QM/MM MD sampling (0.5 ns/profile) the result still depends on the starting structure. The results supported the one step dissociative mechanism of Asp197 glycosylation preceded by an acid-base reaction by the Glu233, which are qualitatively similar to those from multi-PES QM/MM studies, and thus support the use of the latter to determine enzyme reaction mechanisms.     

Efficient kinetic resolution of (±)-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol with the lipase B of Candida antarctica

(±)-1,2-O-Isopropylidene-3,6-di-O-benzyl-myo-inositol is a relevant starting material in the synthesis of inositol phosphates and their analogs. In this study, we disclose our efforts toward an efficient methodology for the kinetic resolution of this compound by lipase B of Candida antarctica (Novozym 435). This reaction selectively affords L-(?)-1,2-O-isopropylidene-5-O-acetyl-3,6-di-O-benzyl-myo-inositol. From a conversion of 34% with EtOAc as an acylating agent, the use of vinyl acetate increased the yield to over 49%, while maintaining a very high ee (>99%). The combination of the latter reagent with TBME as a solvent accelerates the reaction.     

Ambient mass spectrometry: bringing MS into the “real world”

Mass spectrometry has recently undergone a second contemporary revolution with the introduction of a new group of desorption/ionization (DI) techniques known collectively as ambient mass spectrometry. Performed in an open atmosphere directly on samples in their natural environments or matrices, or by using auxiliary surfaces, ambient mass spectrometry (MS) has greatly simplified and increased the speed of MS analysis. Since its debut in 2004 there has been explosive growth in the applications and variants of ambient MS, and a very comprehensive set of techniques based on different desorption and ionization mechanisms is now available. Most types of molecules with a large range of masses and polarities can be ionized with great ease and simplicity with the outstanding combination of the speed, selectivity, and sensitivity of MS detection. This review describes and compares the basis of ionization and the concepts of the most promising ambient MS techniques known to date and illustrates, via typical analytical and bioanalytical applications, how ambient MS is helping to bring MS analysis deeper than ever into the “real world” open atmosphere environment—to wherever MS is needed.