Amides, protonation

Tjandra N and Bax A 1997 Solution NMR measurement of amide proton chemical shift anisotropy in N-15-enriched proteins. Correlation with hydrogen bond length J. Am. Chem. Soc. 119 8076-82... 

Consider a nucleus that can partition between two magnetically nonequivalent sites. Examples would be protons or carbon atoms involved in cis-trans isomerization, rotation about the carbon—nitrogen atom in amides, proton exchange between solute and solvent or between two conjugate acid-base pairs, or molecular complex formation. In the NMR context the nucleus is said to undergo chemical exchange between the sites. Chemical exchange is a relaxation mechanism, because it is a means by which the nucleus in one site (state) is enabled to leave that state. 

FIGURE 6.5 A hydrogen bond between the amide proton and carbonyl oxygen of adjacent peptide groups. 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

The formation of an intramolecular H-bond is supported by the slower rate of amide proton exchange in pyridine/10% CD3OD. The influence of the stereochemistry on turn formation and turn geometry has been investigated. Seebach and coworkers have demonstrated that dipeptide sequences consisting... 

D-NOESY- H- N-HMQC/HSQC Sequential assignment of the spin system, identification of nOes with amide protons... 

Data concerning plants of occurrence, melting points, and spectral features of these alkaloids have been collected by Krane et al. (6). Some characteristic spectral features deserve attention. In IR spectra the amide band appears in the region between 1670 and 1646 cm-1. Among the H-NMR spectra, singlets of the N-methyl amide protons are situated between 82.91 and 3.27, and the... 

The number of NMR parameters available for measurement is rather small, consisting of the chemical shift, relaxation rates (/1 and lo), scalar (J) couplings, dipolar (D) couplings, cross-relaxation rates (the NOE), and hydrogen exchange rates. All of these have been quantified for many of the amide protons of A131 A, and most of the data suggest the presence of little persistent structure. 

Amide proton temperature coefficients and hydrogen exchange rates can provide information about hydrogen-bonding interactions and solvent sequestration in unfolded or partly folded proteins (Dyson and Wright, 1991). Abnormally low temperature coefficients, relative to random coil values, are a clear indication of local structure and interactions. 

Likewise, amide protons protected from exchange are a useful indication of structured regions in partly folded proteins and molten globules (Hughson etal., 1990). 

Spectrum 6.8 4-Bromobenzamide showing typical appearance of primary amide protons as two non-equivalent broad signals separated by about 0.6 ppm. 

Scheme 19), displays interesting CEST properties when its amide NH resonance is irradiated.192 As the exchange rate of the amide protons is base catalyzed, the complex proves to be an efficient pH-sensitive probe in the 5.5-8.2 pH range. 

Stylotelline (23) is a constituent of a Stylotella sp. collected offshore in New Caledonia. 13C NMR spectra involving 2D NMR techniques provided the bulk of information leading to its structure. The absolute configuration was demonstrated after the tertiary isocyano group was removed to yield the known conjugated diene, ( + )-d-selinene (24). Optical rotation and spectral data of the transformation product were identical in all respects to those of the corresponding product obtained from eudesmols [42], Although neither the isothiocyanato nor the formamido compounds were isolated, the latter was prepared, which allowed an nOe observation between the axial C-3 and the amide protons. 

Hence, chalcogenoamidophosphinic acids of general formula R2P(E)NHR (27) can be considered as dichalcogenophosphinic acids with one of the chalcogen atoms replaced by an amido group. These amido species are still normally referred to as acids due to their acidic amide protons. They are accessible from reaction of thiophosphinic chlorides and primary amines (Equation 43) or from reaction of aminophosphines with elemental chalcogen... 

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