Re: [ccp4bb]: structural basis for amide vs ester hydrolysis?

[Harry M. Greenblatt]

BS"D Its due to the stability of the amide (more stable) compared with the ester. The C-N bond has partial double bond character and is planar compared with the single bond of an ester where only the C=O is planar. Hi, sorry but this theory doesn't accord with observation: for non-conjugated acyclic esters in the CSD the RMSD of the C-O torsion about the mean (= 0) is ~ 4.7 deg; for non-conjugated acyclic primary amides it's well known that the RMSD of the C-N torsion is ~ 6.0 deg (mean = -1.0), so on average the ester is actually slightly more planar than the amide.  In the case of esters, it is still possible to draw a resonance structure which puts a double bond between the carbon atom and the ester oxygen.  In this resonance structure the carbonyl oxygen bears a formal negative charge, and the ester oxygen bears a formal positive charge.  This is one of the two reasons given for the shortening of this carbon-oxygen bond.  The contribution of this resonance structure, however, is assumed to be less significant than in the case of amides, since oxygen is more electronegative than nitrogen, and so is less "happy" bearing a formal positive charge.         So one does expect ester systems,  in the absence of distorting factors, to show planarity,  but they are not as rigid as the amide system.  In amides the rotation barrier is quite high (about 18kcal/mole).     Why Ian sees a greater tendency to planarity on the part of esters is interesting.  Perhaps there is some hidden factor in his choice of model structures which is biasing the results. Harry ------------------------------------------------------------------------- Harry M. Greenblatt Staff Scientist Dept of Structural Biology           [EMAIL PROTECTED] Weizmann Institute of Science        Phone:  972-8-934-3625 Rehovot, 76100                       Facsimile:   972-8-934-4159 Israel