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Cleavages in stable tetrahedral intermediates' bonds and the role of water
Author(s) -
Bethencourt Loengrid,
Vivas Daniel,
Núñez Oswaldo
Publication year - 2010
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1725
Subject(s) - chemistry , tetrahedral carbonyl addition compound , heteroatom , proteases , stereochemistry , cleavage (geology) , protonation , serine , bond cleavage , tetrahedron , tetrahedral molecular geometry , ring (chemistry) , enzyme , crystallography , molecule , catalysis , organic chemistry , ion , geotechnical engineering , fracture (geology) , engineering , nucleophile
Using two‐dimensional energy diagrams, results on the formation and cleavage of detectable tetrahedral intermediates are used to predict the position of transition states involved in the cleavages of unstable and stable tetrahedral intermediates (STI). A late transition state (anti‐Hammond) for the former and synchronous cleavage for the latter are predicted and supported with experimental results. For instance, in the case of STI, intrinsic leaving abilities in the order CO > CNHCO ≫ CNH were experimentally observed, confirming the departure of these groups without full heteroatom protonation. The STI designed herein mimics serine proteases enzymes due to the thermoneutral relationship between the enzyme substrate (ES) and enzyme‐acyl tetrahedral intermediate (EATI) analogs. In the STI models, a dramatic change in pKa is observed when changing the lactam ring size due to the strain in the 3‐fused‐ring system of the STI‐H 2 O complex formed and exo‐anomeric effect. A plot of Δ S o (STI formation) versus pK a provides evidence for the STI–water interaction. Since only one water molecule is required to produce the effect it is also detected when using ‘pure’ CDCl 3 as the solvent and therefore may also play a role in the active sites of serine proteases. Copyright © 2010 John Wiley & Sons, Ltd.