Biomedical subjects

Geoffrey P F Wood

Publications and source records attributed to Geoffrey P F Wood.

3 recordsLinked to original sources

PubMed2006

A restricted-open-shell complete-basis-set model chemistry.

A restricted-open-shell model chemistry based on the complete basis set-quadratic Becke3 (CBS-QB3) model is formulated and denoted ROCBS-QB3. As the name implies, this method uses spin-restricted wave functions, both for the direct calculations of the various components of the electronic energy and for extrapolating the correlation energy to the complete-basis-set limit. These modifications eliminate the need for empirical corrections that are incorporated in standard CBS-QB3 to compensate for spin contamination when spin-unrestricted wave functions are used. We employ an initial test set of 19 severely spin-contaminated species including doublet radicals and both singlet and triplet biradicals. The mean absolute deviation (MAD) from experiment for the new ROCBS-QB3 model (3.6+/-1.5 kJ mol(-1)) is slightly smaller than that of the standard unrestricted CBS-QB3 version (4.8+/-1.5 kJ mol(-1)) and substantially smaller than the MAD for the unrestricted CBS-QB3 before inclusion of the spin correction (16.1+/-1.5 kJ mol(-1)). However, when applied to calculate the heats of formation at 298 K for the moderately spin-contaminated radicals in the G2/97 test set, ROCBS-QB3 does not perform quite as well as the standard unrestricted CBS-QB3, with a MAD from experiment of 3.8+/-1.6 kJ mol(-1) (compared with 2.9+/-1.6 kJ mol(-1) for standard CBS-QB3). ROCBS-QB3 performs marginally better than standard CBS-QB3 for the G2/97 set of ionization energies with a MAD of 4.1+/-0.1 kJ mol(-1) (compared with 4.4+/-0.1 kJ mol(-1)) and electron affinities with a MAD of 3.9+/-0.2 kJ mol(-1) (compared with 4.3+/-0.2 kJ mol(-1)), but the differences in MAD values are comparable to the experimental uncertainties. Our overall conclusion is that ROCBS-QB3 eliminates the spin correction in standard CBS-QB3 with no loss in accuracy.

Journal Article↗

PubMed2006

Effect of side chains on competing pathways for beta-scission reactions of peptide-backbone alkoxyl radicals.

High-level quantum chemistry calculations have been carried out to investigate beta-scission reactions of alkoxyl radicals located at the alpha-carbon of a peptide backbone. This type of alkoxyl radical may undergo three possible beta-scission reactions, namely C-C beta-scission of the backbone, C-N beta-scission of the backbone, and C-R beta-scission of the side chain. We find that the rates for the C-C beta-scission reactions are all very fast, with rate constants of the order 10(12) s(-1) that are essentially independent of the side chain. The C-N beta-scission reactions are all slow, with rate constants that range from 10(-0.7) to 10(-4.5) s(-1). The rates of the C-R beta-scission reactions depend on the side chain and range from moderately fast (10(7) s(-1)) to very fast (10(12) s(-1)). The rates of the C-R beta-scission reactions correlate well with the relative stabilities of the resultant side-chain product radicals (*R), as reflected in calculated radical stabilization energies (RSEs). The order of stabilities for the side-chain fragment radicals for the natural amino acids is found to be Ala < Glu < Gln approximately Leu approximately Met approximately Lys approximately Arg < Asp approximately Ile approximately Asn approximately Val < Ser approximately Thr approximately Cys < Phe approximately Tyr approximately His approximately Trp. We predict that for side-chain C-R beta-scission reactions to effectively compete with the backbone C-C beta-scission reactions, the side-chain fragment radicals would generally need an RSE greater than approximately 30 kJ mol(-1). Thus, the residues that may lead to competitive side-chain beta-scission reactions are Ser, Thr, Cys, Phe, Tyr, His, and Trp.

Alcohols↗

PubMed2005

Bond dissociation energies and radical stabilization energies associated with model peptide-backbone radicals.

Bond dissociation energies (BDEs) and radical stabilization energies (RSEs) have been calculated for a series of models that represent a glycine-containing peptide-backbone. High-level methods that have been used include W1, CBS-QB3, U-CBS-QB3, and G3X(MP2)-RAD. Simpler methods used include MP2, B3-LYP, BMK, and MPWB1K in association with the 6-311+G(3df,2p) basis set. We find that the high-level methods produce BDEs and RSEs that are in good agreement with one another. Of the simpler methods, RBMK and RMPWB1K achieve good accuracy for BDEs and RSEs for all the species that were examined. For monosubstituted carbon-centered radicals, we find that the stabilizing effect (as measured by RSEs) of carbonyl substituents (CX=O) ranges from 24.7 to 36.9 kJ mol(-1), with the largest stabilization occurring for the CH=O group. Amino groups (NHY) also stabilize a monosubstituted alpha-carbon radical, with the calculated RSEs ranging from 44.5 to 49.5 kJ mol(-1), the largest stabilization occurring for the NH2 group. In combination, NHY and CX=O substituents on a disubstituted carbon-centered radical produce a large stabilizing effect ranging from 82.0 to 125.8 kJ mol(-1). This translates to a captodative (synergistic) stabilization of 12.8 to 39.4 kJ mol(-1). For monosubstituted nitrogen-centered radicals, we find that the stabilizing effect of methyl and related (CH2Z) substituents ranges from 25.9 to 31.7 kJ mol(-1), the largest stabilization occurring for the CH3 group. Carbonyl substituents (CX=O) destabilize a nitrogen-centered radical relative to the corresponding closed-shell molecule, with the calculated RSEs ranging from -30.8 to -22.3 kJ mol(-1), the largest destabilization occurring for the CH=O group. In combination, CH2Z and CX=O substituents at a nitrogen radical center produce a destabilizing effect ranging from -19.0 to -0.2 kJ mol(-1). This translates to an additional destabilization associated with disubstitution of -18.6 to -7.8 kJ mol(-1).

Carbon↗