Surroundings of Carboxylate Groups

The lone-pair electrons in a carboxylate group are designated syn or antiy as shown in Fig. 18. The proton on another molecule can approach in either of these directions. In the syn conformation (Z-form) the proton is on the same side of the C-0 bond as the other C-0 bond this is the conformation found when carboxyl groups dimerize by forming two hydrogen bonds. On the other hand, in the anti conformation (E-form) the proton is on the opposite side of the C-0 bond from the other C-0 bond. Ab initio quantum chemical studies of formic acid indicate that the syn (Z) conformation is more stable than the anti (E) conformation by about 4.5 kcal mol implying that the syn lone pairs are more basic (and therefore bind metal ions more readily) than do the anti lone pairs [55]. Carboxylates in active sites of enzymes generally seem to employ the more basic syn lone pairs for metal chelation [56], and it has been estimated that syn protonation is 10 -fold more favorable than anti protonation (since 1.4 kcal mol corresponds approximately to a tenfold increase in rate). The carboxylate ion is therefore a weaker base when constrained to accept a proton in the anti (E) direction. 

These results are also found in protein crystal structures [58]. Here carboxylate groups are found in aspartate and glutamate side chains. When ligands 

When the carboxyl group is not ionized it is found, from detailed neutron diffraction studies, that the hydroxyl portion of the carboxyl group, while a powerful hydrogen-bond donor, does not accept hydrogen bonds [59]. This information can be used to assign ionization states in protein crystal structures in which hydrogen atoms are not located. The results for lysozyme, shown in Fig. 19, were in line with those deduced by other methods. 

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