The chemistry of Alzheimer’s disease is largely centred on the amyloid β-peptide, its formation, structure, and interactions with metals, membranes, proteins and other species. This critical review summarizes the current state of knowledge (252 references).

The reactions of methanethiyl radicals (CH₃S˙) with the cyclic anhydrides of glycine (1a), alanine (L,L-1b and D,L-1b), and sarcosine (1c), and the acyclic peptides, N-formylglycinamide (3a) and N-formylalaninamide (3b), were studied by means of theoretical calculations at the B3LYP/6-311+G(d,p) level of theory. Free energies in the gas phase were determined in the classical harmonic oscillator-rigid rotator model, and used to estimate rates of H-transfer reactions at the ^αC-site of the peptides. The effects of aqueous solution were estimated by the SCIPCM procedure in combination with modified experimental Arrhenius A-factors to calculate solution phase rate constants. The reactions are discussed in terms of the charge and spin polarisation in the transition state, as determined by AIM analysis. Rate constants calculated by this semiempirical Arrhenius approach are in very good agreement with available experimental data on the reaction of D₃N⁺CH₂CH₂S˙ with 1a and 1c but not 1b in D₂O. The rate constants for the reaction of CH₃S˙ with 3a and 3b are also in very good agreement with experimental data on the N-acetyl analogues. Contrary to experiment, the cyclic alanine anhydrides, L,L-1b and D,L-1b, were predicted to react more than an order of magnitude more quickly than any of the other dipeptides.

The Arrhenius parameters and rates of reaction of three hydroxyradicals, methyl radical, and the hindered primary C-centred radical from t-butyl alcohol with dithiothreitol were measured by pulse radiolysis in water. The bimolecular rate constants were found to be in the order: ˙C(CH₃)₂OH > ˙CH(CH₃)OH > ˙CH₂OH > ˙CH₃ > ˙CH₂C(CH₃)₂OH. The reaction of three of these, ˙C(CH₃)₂OH, ˙CH₂OH, and ˙CH₃, with methanethiol were examined at the ab initio B3LYP/6311+G(d,p) level, coupled with transition state theory, both in the gas phase and in solution. The solvent effects are evaluated by two different continuum models (SCIPCM, CPCM), coupled with a novel approach to the calculation of the solution phase entropy. The reaction is discussed in terms of the charge and spin polarization in the transition state, as determined by AIM analysis, and in terms of orbital interaction theory. Rate constants, calculated by transition state theory are in good agreement with the experimental data.