Chemical exchange acidic protons

Consider a nucleus that can partition between two magnetically nonequivalent sites. Examples would be protons or carbon atoms involved in cis-trans isomerization, rotation about the carbon—nitrogen atom in amides, proton exchange between solute and solvent or between two conjugate acid-base pairs, or molecular complex formation. In the NMR context the nucleus is said to undergo chemical exchange between the sites. Chemical exchange is a relaxation mechanism, because it is a means by which the nucleus in one site (state) is enabled to leave that state. 

Much information on proton transfers has been obtained by NMR chemical exchange studies. An example is the proton exchange between neopentyl alcohol and acetic acid in acetic acid as the solvent. The reaction is... 

The occurrence of an average CH3-CO resonance line position from acetic acid and TBT acetate is a consequence of rapid chemical exchange of the tributyltin group. It represents the CH3-CO protons in a time-averaged environment. 

Proton transfers are particularly common. This acid-base catalysis by enzymes is much more effective than the exchange of protons between acids and bases in solution. In many cases, chemical groups are temporarily bound covalently to the amino acid residues of the enzyme or to coenzymes during the catalytic cycle. This effect is referred to as covalent catalysis (see the transaminases, for example p. 178). The principles of enzyme catalysis sketched out here are discussed in greater detail on p. 100 using the example of lactate dehydrogenase. 

Carboxylic Acid Protons Because carboxylic acid protons are bonded to an oxygen next to a carbonyl group, they have considerable positive character. They are strongly deshielded and absorb at chemical shifts greater than 510. Carboxylic acids frequently exist as hydrogen-bonded dimers (shown at left), with moderate rates of proton exchange that broaden the absorption of the acid proton. 

Resonances A and B are slowly-exchanging hydroxyl protons they exchange on addition of acid, and this decouples them from C and G. C, the carbon-bound proton with the largest chemical shift, is likely to be on the anomeric carbon with two attached oxygens. D and E are distinguished by the number of couplings. F and H may be reversed. 

In metallothioneins, the metal-free protein or apoMT, appears to possess a predominantly disordered structme. This conclusion has been drawn from H NMR studies of apoMT in which the chemical shifts of proton resonances are comparable with those observed in amixture of the constituent amino acids. In addition, the rapid exchange rate of the amide protons in... 

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