Effect of ortho-SR groups on O-H bond strength and H-atom donating ability of phenols: a possible role for the Tyr-Cys link in galactose oxidase active site?

Rotation about the Ar-S bond in ortho-(alkylthio)phenols strongly affects the bond dissociation enthalpy (BDE) and the reactivity of the OH group. Newly synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost coplanar with the phenolic ring, are characterized by unusually low BDE(O-H) values (79.6 and 79.2 kcal/mol, respectively) and by much higher reactivities toward peroxyl radicals than the ortho-methylthio derivative 1 (82.0 kcal/mol). The importance of the intramolecular hydrogen bond (IHB) in determining the BDE(O-H) was demonstrated by FT-IR experiments, which showed that in heterocycles 3 and 4 the IHB between the phenolic OH group and the S atom is much weaker than that present in 1. Since the IHB can be formed only if the -SR group adopts an out-of-plane geometry, this interaction is possible only in the methylthio derivative 1 and not in 3 and 4. The additive contribution to the phenolic BDE(O-H) of the -SR substituent therefore varies from -3.1 to +2.8 kcal/mol for the in-plane and out-of-plane conformations, respectively. These results may be relevant to understanding the role of the tyrosine-cysteine link in the active site of galactose oxidase, an important enzyme that catalyzes the two-electron aerobic oxidation of primary alcohols to aldehydes. The switching of the ortho -SR substituent between perpendicular and planar conformations may account for the catalytic efficiency of this enzyme.     

Insights into 6‐Methylsalicylic Acid Bio‐assembly by Using Chemical Probes

Chemical probes capable of reacting with KS (ketosynthase)‐bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6‐methylsalicylic acid synthase (6‐MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6‐MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6‐MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities.     

Artarborol, a nor-caryophyllane sesquiterpene alcohol from Artemisia arborescens. stereostructure assignment through concurrence of NMR data and computational analysis

A nor-caryophyllane derivative, artarborol, has been isolated from wormwood (Artemisia arborescens) and its stereostructure established by using a combination of chemical derivatization, NMR data, molecular modeling, and quantum-mechanical calculations. In particular, comparison of experimental 13C NMR data with a Boltzmann-weighed average of 13C NMR chemical shifts, calculated by ab initio DFT method, supported the stereochemical assignment.     

Classification of water molecules in protein binding sites

Water molecules play a crucial role in mediating the interaction between a ligand and a macromolecular receptor. An understanding of the nature and role of each water molecule in the active site of a protein could greatly increase the efficiency of rational drug design approaches: if the propensity of a water molecule for displacement can be determined, then synthetic effort may be most profitably applied to the design of specific ligands with the displacement of this water molecule in mind. In this paper, a thermodynamic analysis of water molecules in the binding sites of six proteins, each complexed with a number of inhibitors, is presented. Two classes of water molecules were identified: those conserved and not displaced by any of the ligands, and those that are displaced by some ligands. The absolute binding free energies of 54 water molecules were calculated using the double decoupling method, with replica exchange thermodynamic integration in Monte Carlo simulations. It was found that conserved water molecules are on average more tightly bound than displaced water molecules. In addition, Bayesian statistics is used to calculate the probability that a particular water molecule may be displaced by an appropriately designed ligand, given the calculated binding free energy of the water molecule. This approach therefore allows the numerical assessment of whether or not a given water molecule should be targeted for displacement as part of a rational drug design strategy.     

Biocatalytic Generation of Molecular Diversity: Modification of Ginsenoside Rb1 by β‐1,4‐Galactosyltransferase and Candida antarctica Lipase,Part 4

A series of specific derivatives of the complex protopanaxadiol glycoside ginsenoside Rb₁ ( 1 ) were prepared by catalysis of two unrelated enzymes: the β‐1,4‐galactosyltransferase from bovine colostrum (GalT) and the lipase B from Candida antarctica (Novozym ^® 435). Both of the enzymes showed the expected regioselectivity towards specific glucose OH groups (i.e., OH C(4) for GalT and preferentially the primary OH C(6) for Novozym ^® 435), accompanied by a nonpredictable ‘site selectivity' for the gentiobiose disaccharide unit linked at C(20) of the dammarane skeleton. The galactosylated products 1a – e and the acetylated products 1f – h were isolated by HPLC and fully characterized by extensive MS and NMR analysis.     

The 100 facets of the Passerini reaction

This perspective aims at celebrating the 100th anniversary of the discovery of the Passerini three component reaction. After being nearly neglected for many years, now this reaction has become quite popular, thanks to the achievements of the last 30 years, which have revealed several chances of exploitation in organic synthesis. Though not being comprehensive, this review means to show the various ways that have been used in order to expand the utility of the Passerini reaction. Post-MCR transformations to give heterocycles or peptidomimetics, variants through single component replacement, stereochemical issues, and applications in total syntheses will be especially covered.

This perspective aims at celebrating the 100th anniversary of the discovery of the Passerini three component reaction.     

A new type of luminescent alkynyl Au4Cu2 cluster

Changes in the optical properties of an alkynyldigold(I) complex upon reaction with Cu(I) are associated with a complicated structural change to form an unusual Au4Cu2 cluster with metallophilic interactions as well as pi-alkyne coordination.     

Mobility and Interaction of Heavy Metals in a Natural Soil

We study the mobility and interaction under competing conditions observed for copper ( $\text{ Cu}^{2+}$ ) and zinc ( $\text{ Zn}^{2+}$ ) ions in the context of laboratory-scale experiments performed in natural soil columns. The experiments focus on the analysis of solute breakthrough curves (BTCs) obtained after injection of an aqueous solution containing similar concentrations of the two metal ions into a soil column fully saturated with double deionized water. Transport of the competing ions is tested for the same soil under aerobic and anaerobic conditions. Measurements show that the species with lower affinity for the soil, $\text{ Zn}^{2+}$ , migrates occupying all available adsorption sites, and is then progressively replaced by the ion with higher affinity, $\text{ Cu}^{2+}$ . The two ions are displaced in the system with different effective retardation. The slowest species replaces the sorbed ions, resulting in observed $\text{ Zn}^{2+}$ concentrations that display a non-monotonic behavior in time and which, for a certain period, are larger than the concentration supplied continuously at the inlet. In the absence of a complete geochemical characterization of the system, we show that the measured concentrations of both metals can be interpreted through simple models based on a set of coupled partial differential and algebraic equations, involving a small subset of aqueous and adsorbed species that are present in the system. Depending on the model considered, the relationship between aqueous and adsorbed ion concentrations is described at equilibrium by a Gaines–Thomas (GT) formulation, a competitive Sheindorf–Rebhun–Sheintuch (SRS) isotherm, or an Extended Langmuir (EL) isotherm, respectively. The GT formulation provides the best interpretation of the observed behavior among the models tested. We find that employing these simple models, which account only for the main governing reactive processes, allows reasonable estimation of the observed BTCs in experiments where only partial geochemical datasets are available.