Gregory A. Chass

Recycling the waste: the development of a catalytic wittig reaction.

The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt. The geometry of the resulting alkene depends on the reactivity of the ylide. If R is an electron withdrawing group, then the ylide is stabilized and is not as reactive as when R is alkyl. Stabilized ylides give predominantly (E)-alkenes whereas non-stabilized ylides lead to (Z)-alkenes (see also Wittig-Horner Reaction).

Persistently Folded Circular Aromatic Amide Pentamers Containing Modularly Tunable Cation-Binding Cavities with High Ion Selectivity

In this work, we illustrated a novel design strategy that allows systematically tunable interior properties (effective cavity size, steric crowdedness, and hydrophobicity) contained within a novel class of shape-persistent aromatic pentamers to take place on a scale below 3 A. Such finely tunable structural features are complimented by experimentally observable functional variations in ion-binding potential. Results of the selective, differential binding affinities of three circular pentamers for Li(+), Na(+), K(+), Rb(+), and Cs(+), substantiated by metal-containing crystal structures and computational modeling, are detailed.

Pd(OAc)2-catalyzed C-H activation/C-O cyclization: mechanism, role of oxidant-probed by density functional theory.

A series of density functional theory determinations have been carried out to characterize Pd(OAc)2-catalyzed C-H activation and subsequent intramolecular C-O bond-coupling of phenyl-tert-butanol in perfluorobenzene (C6F6) solvent. Full, nontruncated models of the real chemical transformations were studied, with structures in agreement with recent X-ray determinations. Conformational analyses have provided thermodynamic validity of the geometric structures used. The B3LYP/DZVP and B3LYP/BS1 methods (BS1 = TZVP(H,C,O) + SDD(Pd,I)) were comparatively employed, with C6F6 solvent contributions accounted for by the IDSCRF method; key transition states were confirmed by intrinsic reaction coordinate determinations. The novel reaction mechanism proposed was divided into the following four steps: C-H activation, oxidation, reductive elimination, catalyst recovery. Two competing reaction routes were quantitatively compared, differing in the oxidation state of Pd (+2 vs +4). Results reveal the pathway involving Pd(IV) intermediates to be more spontaneous and, therefore, more probable than the Pd(II) path, the latter hindered by a kinetically inaccessible reductive elimination step, with total energy and free energy barriers of 41.0 and 38.6 kcal·mol(-1), respectively. The roles played by the oxidant and Pd(IV) species have also been addressed through Baders atoms-in-molecules wave function analyses, providing a quantitative electronic metric for C-H activation chemistry.

Amidicity change as a significant driving force and thermodynamic selection rule of transamidation reactions. A synergy between experiment and theory

Although essential in medicinal and industrial chemistry, transamidation reactions are still poorly understood mechanistically and in particular in terms of the extreme nature for their proceeding either very smoothly or not occurring at all. As yet, there exists no qualitative rule to predict the outcome of an amide interacting with an amine, with quantitative evaluations far from being established. In this paper we aim to clarify the thermodynamic selection rule and driving force of transamidation reactions based on amidicity value, measuring numerically the amide bond strength, toward providing a relatively simple protocol for practicing organic chemists to predict the outcome of an experiment. The change of amidicity over the course of a reaction made it possible to see that the process is favorable or unfavorable. This recently evaluated driving force of amidicity behaves analogously to the driving force of aromaticity in other organic reactions. This paper presents a successful comparison between empirical synthetic results and relevant computational characterizations, for a variety of transamidation reactions, all toward a synergy between experiments and theory. In this paper, we are re-examining experimentally and theoretically earlier experimental findings in relation to transamidation reactions and interpreting them from the aspect of amidicity change and stabilization enthalpies.

Vitamin E models. Shortened sidechain models of α, β, γ and δ tocopherol and tocotrienol: a density functional study

Model compounds of α-, β-, γ-, and δ-tocopherol and Tocotrienol, as well as their sulphur and selenium congeners, were subjected to density functional analysis. The mono methyl substitution either stabilized or destabilized the ring structures to a small extent as assessed in terms of isodesmic reactions. In general, multiple methyl substitutions destabilized the ring. Dimethyl para-substitution results in electronic stabilization and steric repulsion being nearly additive. This was not the case for ortho-dimethyl derivatives, whereby steric repulsions dominate; the meta-substituted models reflect the same trend to a lesser degree. Structurally, the phenolic hydroxyl orientation was approximately planar, with the hydroxyl proton oriented away from the adjacent Me group whenever the structure permitted such an orientation.

Vitamin E models. Can the anti-oxidant and pro-oxidant dichotomy of α-tocopherol be related to ionic ring closing and radical ring opening redox reactions?

Abstract The free radical scavenging mechanism, leading to a quinodal structure via an oxidative ring opening is exothermic. However, the ionic oxidative ring opening is endothermic. Consequently, the ionic reductive ring closing must be exothermic. This leads to the suggestion that Vitamin E may be recovered, unchanged, thus effectively acts as a catalyst for the following reaction 2 HOO + H 3 O (+) + NADH →2 HOOH + H 2 O + NAD (+) , Δ E≈−120 kcal mol −1 . As Vitamin E is biologically recycled, a single α-tocopherol molecule may convert numerous HOO radical to H2O2 which is accumulated if not removed at the same rate, enzymatically, with the participation of catalase (Fe) or glutathione peroxidase, GPx(Se). This accumulation of peroxide, which may be referred to as a ‘peroxide traffic jam’, may well be the reason of the pro-oxidant effect of Vitamin E.

Atomic and vibrational origins of mechanical toughness in bioactive cement during setting

Bioactive glass ionomer cements (GICs) have been in widespread use for ∼40 years in dentistry and medicine. However, these composites fall short of the toughness needed for permanent implants. Significant impediment to improvement has been the requisite use of conventional destructive mechanical testing, which is necessarily retrospective. Here we show quantitatively, through the novel use of calorimetry, terahertz (THz) spectroscopy and neutron scattering, how GICs developing fracture toughness during setting is related to interfacial THz dynamics, changing atomic cohesion and fluctuating interfacial configurations. Contrary to convention, we find setting is non-monotonic, characterized by abrupt features not previously detected, including a glass–polymer coupling point, an early setting point, where decreasing toughness unexpectedly recovers, followed by stress-induced weakening of interfaces. Subsequently, toughness declines asymptotically to long-term fracture test values. We expect the insight afforded by these in situ non-destructive techniques will assist in raising understanding of the setting mechanisms and associated dynamics of cementitious materials.

Conformational effects of one glycine residue on the other glycine residues in the Ac-Gly-Gly-Gly-NHMe tripeptide motif: an ab initio exploratory study

Abstract Ab initio molecular computations were carried out on the tripeptide model, Ac-Gly-Gly-Gly-NHMe at the RHF/3-21G ab initio level of theory. Two of the glycine residues were chosen at a time to be in the fully extended, or β (C 5 ) conformation, in order to monitor the effects on the third residue with varying the backbone conformation. The topologies of each of the three Ramachandran type conformational potential energy surfaces were analyzed and five minima (β, γ l , γ d , δ l , δ d ) associated with each one of the three glycine residues, were located for each surface.

Density functional molecular computations on protonated serotonin in the gas phase and various solvent media

Abstract 5-Hydroxytryptamine (serotonin) was geometry optimized at the B3YP/6-31G(d) level of theory to determine the energetically most favourable conformations of the aromatic hydroxyl group and the protonated ethylamine side chain. The hydroxyl group was found to be most stable at anti for all conformations, and the two lowest energy gas phase conformers found were: χ 2 = g + , χ 3 = g − and χ 2 = g − , χ 3 = g + . The protonated amino group was found equally stable at g + , g − and anti . The transition structures linking each gas phase minimum were also computed. Minima found were subjected to solvation calculations in chloroform, DMSO, ethanol and water, which shifted their relative stabilities.

Generation and analysis of the conformational potential energy surfaces of N-acetyl-N-methyl-L-alanine-N'-methylamide. An exploratory ab initio study

Abstract N-methylation is a naturally occurring modification in small peptides, e.g. antibiotics that can effect the conformational preferences of the molecule as well as the ease of trans to cis isomerization of the involved peptide bond. In the present exploratory study we have calculated the potential energy surface of both N -acetyl- l -alanine- N ′-methylamide and N -acetyl- N -methyl- l -alanine- N ′-methylamide at the RHF/3-21G level of theory with a cis – trans or with a trans – trans peptide conformation. With respect to the non-methylated model system our results indicate that N-methylation reduces the number of observable backbone conformers in both amide configurations. The effect of methylation on the ease of trans to cis isomerization was assessed by calculating the energetics of the corresponding transition structures. An increase in the activation energies of the trans to cis isomerization of the relevant peptide bond was observed for the N-methylated moiety.