Carboxylate groups anti conformation

A prototype of such phenomena can be seen in even the simplest carboxylic acid, acetic acid (CH3CHOOH). Acidity is determined by the energy or free energy difference between the dissociated and nondissociated forms, whose energetics usually depend significantly on their conformation, e.g., the syn/anti conformational change of the carboxyl-ate group in the compound substantially affects the acid-base equilibrium. The coupled conformation and solvent effects on acidity is treated in Ref. 20. 

The crystal structures of the salts of 10 with racemic amines showed that there is a favorable and common conformation for the anions of 10 [(10a-H)-, (10b-H), (10a-2H)2-, and (10b-2H)2- ] in the crystalline state (Figure 4.31) four carbon atoms (C1-C4) are almost on the same plane, and two carboxylate groups are in an anti conformation while two benzoyl or toluoyl groups are gauche to each other.92... 

In RmL, 081 of Asp-203 accepts a syn-type H-bond from N81 of His-257 and an anti-type bond from Or/ of Tyr-260 (Fig. 5A). On the other hand, 082 is within a small distance of both N81 of His-257 (3.02 A) and the main-chain N of Val-205 (2.97 A). However, in the former case the angle on the hydrogen atom (082 H—Ne2) is much too acute ( 80°) for a strong H-bond. It is therefore the interaction with Val-205 that is relevant with respect to the stabilization of the side-chain conformation of Asp-203. This stereochemistry is very close to that found in chymotrypsin (Fig. 5B), where 081 of Asp-102 also accepts two H-bonds a syn type from Ne2 of His-57 and an anti from the hydroxyl of Ser-114. The overall effect is such that in lipases and in chymotrypsin the carboxyl group of the catalytic Asp is oriented in the same way with respect to the plane of the imidazole of the catalytic histidine. 

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. 

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