of the following four structural features: polycyclic structures (e.g. tetrodotoxin) compounds with a strong electron-withdrawing group attached to the acyl carbon (e.g. N,N-dimethyltrifluoroacetamide) compounds with donor groups that are poorly conjugated with the potential carbonyl group (e.g. cyclol) compounds with sulfur atoms bonded to the anomeric centre (e.g., ) These compounds were used to study the kinetics of tetrahedral intermediate decomposition into its respective carbonyl species, and to measure the IR, UV, and NMR spectra of the tetrahedral adduct. X-ray crystal structure determination The first X-ray crystal structures of tetrahedral intermediates were obtained in 1973 from bovine trypsin crystallized with bovine pancreatic trypsin inhibitor, and in 1974 from porcine trypsin crystallized with soybean trypsin inhibitor. In both cases the tetrahedral intermediate is stabilized in the active sites of enzymes, which have evolved to stabilize the transition state of peptide hydrolysis. Some insight into the structure of tetrahedral intermediate can be obtained from the crystal structure of N-brosylmitomycin A, crystallized in 1967. The tetrahedral carbon C17 forms a 136.54 pm bond with O3, which is shorter than C8-O3 bond (142.31 pm). In contrast, C17-N2 bond (149.06 pm) is longer than N1-C1 bond (148.75 pm) and N1-C11 bond (147.85 pm) due to donation of O3 lone pair into σ* orbital of C17-N2. This model however is forced into tetracyclic sceleton, and tetrahedral O3 is methylated which makes it a poor model overall. The more recent x-ray crystal structure of 1-aza-3,5,7-trimethyladamantan-2-one is a good model for cationic tetrahedral intermediate. The C1-N1 bond is rather long [155.2(4) pm], and C1-O1(2) bonds are shortened [138.2(4) pm]. The protonated nitrogen atom N1 is a great amine leaving group. In 2002 David Evans et al. observed a very stable neutral tetrahedral intermediate in the reaction of N-acylpyrroles with organometallic compounds, followed by protonation with ammonium chloride producing a carbinol. The C1-N1 bond [147.84(14) pm] is longer than the usual Csp3-Npyrrole bond which range from 141.2-145.8 pm. In contrast, the C1-O1 bond [141.15(13) pm] is shorter than the average Csp3-OH bond which is about 143.2 pm. The elongated C1-N1, and shortened C1-O1 bonds are explained with an anomeric effect resulting from the interaction of the oxygen lone pairs with the σ*C-N orbital. Similarly, an interaction of an oxygen lone pair with σ*C-C orbital should be responsible for the lengthened C1-C2 bond [152.75(15) pm] compared to the average Csp2-Csp2 bonds which are 151.3 pm. Also, the C1-C11 bond [152.16(17)