Proton-transport catalysis, proton abstraction, and proton exchange in HF+HOC⁺ and H₂O+HOC⁺ and analogous deuterated reactions

Classical simulations of the reactions of HF and H₂O with HOC⁺ have been carried out on interpolatedab initiopotential energy surfaces. Rearrangement (X+HOC⁺→OCH⁺+X), abstraction (X+HOC⁺→XH⁺+OC), (X=HF or H₂O), exchange (e.g., DY+HOC⁺→HY+DOC⁺), and exchange-rearrangement (e.g., DY+HOC⁺→OCD⁺+YH) (Y=F or HO or DO) reactions are observed. However, the abstraction reaction is dominant for both the HF+HOC⁺ and H₂O+HOC⁺ systems

G3-RAD and G3X-RAD: Modified Gaussian-3 (G3) and Gaussian-3X (G3X) procedures for radical thermochemistry

The G3-RAD, G3X-RAD, G3(MP2)-RAD, and G3X(MP2)-RAD, procedures, designed particularly for the prediction of reliable thermochemistry for free radicals, are formulated and their performance assessed using the G2/97 test set. The principal features of the RAD procedures include (a) the use of B3-LYP geometries and vibrational frequencies (in place of UHF and UMP2), including the scaling of vibrational frequencies so as to reproduce ZPVEs, (b) the use of URCCSD(T) [in place of UQCISD(T)] as the highest-level correlation procedure, and (c) the use of RMP (in place of UMP) to approximate basis-set-extension effects. G3-RAD and G3X-RAD are found to perform well overall with mean absolute deviations (MADs) from experiment of 3.96 and 3.65 kJ mol⁻¹, respectively, compared with 4.26 and 4.02 kJ mol⁻¹ for standard G3 and G3X. G3-RAD and G3X-RAD successfully predict heats of formation with MADs of 3.68 and 3.11 kJ mol⁻¹, respectively (compared with 3.93 and 3.60 kJ mol⁻¹ for standard G3 and G3X), and perform particularly well for radicals with MADs of 2.59 and 2.50 kJ mol⁻¹, respectively (compared with 3.51 and 3.18 kJ mol⁻¹ for standard G3 and G3X). The G3(MP2)-RAD and G3X(MP2)-RAD procedures give acceptable overall performance with mean absolute deviations from experiment of 5.17 and 4.92 kJ mol⁻¹, respectively, compared with 5.44 and 5.23 kJ mol⁻¹ for standard G3(MP2) and G3X(MP2). G3(MP2)-RAD and G3X(MP2)-RAD give improved performance over their standard counterparts for heats of formation (MADs=4.73 and 4.44 kJ mol⁻¹, respectively, versus 4.94 and 4.64 kJ mol⁻¹). G3(MP2)-RAD shows similar performance to G3(MP2) for radical heats of formation (MAD=5.10 versus 5.15 kJ mol⁻¹) while G3X(MP2)-RAD performs significantly better than G3X(MP2) (MAD=4.67 versus 5.19 kJ mol⁻¹).The authors gratefully acknowledge generous allocations of computing time on the Compaq Alphaserver of the National Facility of the Australian Partnership for Advanced Computing, Australian National University Supercomputer Facility, and the support of the Australian Research Council

Nature of Glycine and Its α-Carbon Radical in Aqueous Solution: A Theoretical Investigation

Quantum chemistry calculations and classical molecular dynamics simulations have been used to examine the equilibria in solution between the neutral and zwitterionic forms of glycine and also of the glycyl radical. The established preference (by 30 kJ mol−1) for the zwitterion of glycine was confirmed by both the quantum chemical calculations and the classical molecular dynamics simulations. The best agreement with experiment was derived from thermodynamic integration calculations of explicitly solvated systems, which gives a free energy difference of 36.6 ± 0.6 kJ mol−1. In contrast, for the glycyl radical in solution, the neutral form is preferred, with a calculated free energy difference of 54.8 ± 0.6 kJ mol−1. A detailed analysis of the microsolvation environments of each species was carried out by evaluating radial distribution functions and hydrogen bonding patterns. This analysis provides evidence that the change in preference between glycine and glycyl radical is due to the inherent gas-phase stability of the neutral α-carbon radical rather than to any significant difference in the solvation behavior of the constituent species

Towards Multireference Equivalents of the G2 and G3 Methods

The effect of replacing the standard single-determinant reference wave functions in variants of G2 and G3 theory by multireference (MR) wave functions based on a full-valence complete active space has been investigated. Twelve methods of this type have been introduced and comparisons, based on a slightly reduced G2-1 test set, are made both internally and with the equivalent single-reference methods. We use CASPT2 as the standard MR-MP2 method and MRCl+Q as the higher correlation procedure in these calculations. We find that MR-G2(MP2,SVP), MR-G2(MP2), and MR-G3(MP2) perform comparably with their single-reference analogs, G2(MP2,SVP), G2(MP2), and G3(MP2), with mean absolute deviations (MADs) from the experimental data of 1.41, 1.54, and 1.23 kcal mol−1, compared with 1.60, 1.59, and 1.19 kcal mol−1, respectively. The additivity assumptions in the MR-Gn methods have been tested by carrying out MR-G2/MRCI+Q and MR-G3/MRCI+Q calculations, which correspond to large-basis-set MRCI+Q+ZPVE+HLC calculations. These give MADs of 1.84 and 1.58 kcal mol−1, respectively, i.e., the agreement with experiment is somewhat worse than that obtained with the MR-G2(MP2) and MR-G3(MP2) methods. In a third series of calculations, we have examined pure MP2 and MR-MP2 analogs of the G2 and G3 procedures by carrying out large-basis-set MP2 and CASPT2(+ZPVE+HLC) calculations. The resultant methods, which we denote G2/MP2, G3/MP2, MR-G2/MP2, and MR-G3/MP2, give MADs of 4.19, 3.36, 2.01, and 1.66 kcal mol−1, respectively. Finally, we have examined the effect of using MCQDPT2 in place of CASPT2 in five of our MR-Gn procedures, and find that there is a small but consistent deterioration in performance. Our calculations suggest that the MR-G3(MP2) and MR-G3/MP2 procedures may be useful in situations where a multireference approach is desirable

Towards multireference equivalents of the G2 and G3 methods

The effect of replacing the standard single-determinant reference wave functions in variants of G2 and G3 theory by multireference (MR) wave functions based on a full-valence complete active space has been investigated. Twelve methods of this type have been introduced and comparisons, based on a slightly reduced G2-1 test set, are made both internally and with the equivalent single-reference methods. We use CASPT2 as the standard MR-MP2 method and MRCl+Q as the higher correlation procedure in these calculations. We find that MR-G2(MP2,SVP), MR-G2(MP2), and MR-G3(MP2) perform comparably with their single-reference analogs, G2(MP2,SVP), G2(MP2), and G3(MP2), with mean absolute deviations (MADs) from the experimental data of 1.41, 1.54, and 1.23 kcal mol−1, compared with 1.60, 1.59, and 1.19 kcal mol−1, respectively. The additivity assumptions in the MR-Gn methods have been tested by carrying out MR-G2/MRCI+Q and MR-G3/MRCI+Q calculations, which correspond to large-basis-set MRCI+Q+ZPVE+HLC calculations. These give MADs of 1.84 and 1.58 kcal mol−1, respectively, i.e., the agreement with experiment is somewhat worse than that obtained with the MR-G2(MP2) and MR-G3(MP2) methods. In a third series of calculations, we have examined pure MP2 and MR-MP2 analogs of the G2 and G3 procedures by carrying out large-basis-set MP2 and CASPT2(+ZPVE+HLC) calculations. The resultant methods, which we denote G2/MP2, G3/MP2, MR-G2/MP2, and MR-G3/MP2, give MADs of 4.19, 3.36, 2.01, and 1.66 kcal mol−1, respectively. Finally, we have examined the effect of using MCQDPT2 in place of CASPT2 in five of our MR-Gn procedures, and find that there is a small but consistent deterioration in performance. Our calculations suggest that the MR-G3(MP2) and MR-G3/MP2 procedures may be useful in situations where a multireference approach is desirable.The authors would also like to thank the National Science Foundation International Division for providing travel funds to ~M.S.G. and M.A.F.! and the National Science Foundation Chemistry Division for supporting the research

Hydrogen-atom Attack on Phenol and Toluene is \u3cem\u3eortho\u3c/em\u3e-directed

The reaction of H + phenol and H/D + toluene has been studied in a supersonic expansion after electric discharge. The (1 + 1′) resonance-enhanced multiphoton ionization (REMPI) spectra of the reaction products, at m/z = parent + 1, or parent + 2 amu, were measured by scanning the first (resonance) laser. The resulting spectra are highly structured. Ionization energies were measured by scanning the second (ionization) laser, while the first laser was tuned to a specific transition. Theoretical calculations, benchmarked to the well-studied H + benzene → cyclohexadienyl radical reaction, were performed. The spectrum arising from the reaction of H + phenol is attributed solely to the ortho-hydroxy-cyclohexadienyl radical, which was found in two conformers (syn and anti). Similarly, the reaction of H/D + toluene formed solely the ortho isomer. The preference for the ortho isomer at 100–200 K in the molecular beam is attributed to kinetic, not thermodynamic effects, caused by an entrance channel barrier that is ∼5 kJ mol−1 lower for ortho than for other isomers. Based on these results, we predict that the reaction of H + phenol and H + toluene should still favour the ortho isomer under elevated temperature conditions in the early stages of combustion (200–400 °C)

Rapid Additive-Free Selenocystine–Selenoester Peptide Ligation

We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins

Hydrogen Abstraction by Chlorine Atom from Amino Acids: Remarkable Influence of Polar Effects on Regioselectivity

Quantum chemistry computations have been used to investigate hydrogen-atom abstraction by chlorine atom from protonated and N-acetylated amino acids. The results are consistent with the decreased reactivity at the backbone α-carbon and adjacent side-cha

Preparation of an ion with the highest calculated proton affinity: ortho-diethynylbenzene dianion

Owing to the increased proton affinity that results from additional negative charges, multiply-charged anions have been proposed as one route to prepare and access a range of new and powerful superbases . Paradoxically, while the additional electrons in polyanions increase basicity they serve to diminish the electron binding energy and thus, it had been thought, hinder experimental synthesis. We report the synthesis and isolation of the ortho-diethynylbenzene dianion (ortho-DEB2−) and present observations of this novel species undergoing gas-phase proton-abstraction reactions. Using a theoretical model based on Marcus-Hush theory, we attribute the stability of ortho-DEB2− to the presence of a barrier that prevents spontaneous electron detachment. The proton affinity of 1843 kJ mol−1 calculated for this dianion superbase using high-level quantum chemistry calculations significantly exceeds that of the lithium monoxide anion, the most basic system previously prepared. The ortho-diethynylbenzene dianion is therefore the strongest base that has been experimentally observed to date

Accelerated protein synthesis via one–pot ligation–deselenization chemistry

Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future