Computational Chemistry

The favoring of a diradical mechanism here seems to be an artifact of semiem-
pirical methods (Chapter 6) and unrestricted HF methods (Sections 5.2.3.5 and
5.2.3.6.5); see reference 11 in [ 41 ]. A DFT (Chapter 7) study also strongly sup-
ported the concerted mechanism [ 42 ].

9.1.2.2 Abstraction of H from Amino Acids by the OH· Radical.
Unavoidable Complexity?

This reaction seems more esoteric than the Diels–Alder, and although not “used”,
may be very important. Proteins are linked amino acid residues, and oxidation of
proteins by hydroxyl radicals may initiate Alzheimer’s disease, cancer, and heart
disease. The initial step in the destruction or modification of proteins by hydroxyl
radical is likely to be abstraction of a hydrogen atom from thea–C (Fig.9.6). In a
very thorough study using MP2 (Section 5.4) and DFT (Chapter 7), Galano et al.
calculated the geometries of the species (amino acid–OH complexes, transition
states, and amino acid radicals) involved in the reactions of glycine and alanine
(Fig.9.6,R¼H and CH 3 , respectively) [ 43 ]. The rate constants were also calcu-
lated, using partition functions to calculate the preexponential factor (cf.Sec-
tion 5.5.2.2d). This paper provides a good account of how computational
chemistry can be used to calculate absolute rate constants for reactions of molecules
of moderate size.

9.1.3 Concepts..........................................................

There are some very basic concepts in chemistry that have proved to be helpful in
rationalizing experimental facts, and which have been taught for perhaps the last
50 years, but which have nevertheless been questioned in the last couple decades or
so; an example is the role of resonance in stabilizing species like carboxylate ions.
Some newer concepts, intriguing but not as traditional, have also been scrutinized
and questioned; an example is homoaromaticity.

9.1.3.1 Resonance Versus Inductive Effects

The traditional explanation of the fact that carboxylic acids are much stronger acids
than alcohols is that resonance stabilization of the conjugate base, which is more
important than the charge-separation resonance in the acid, stabilizes RCOO"

HO

C CO 2 H

H

H 2 N

R

CCO 2 H

H 2 N

HOH R

Fig. 9.6 Abstraction of a hydrogen atom from thea–C of an amino acid by hydroxyl radical has
been investigated computationally

568 9 Selected Literature Highlights, Books, Websites, Software and Hardware