Guanidines protonated

Table 2.8 Computationally estimated PAs and pK values for guanidine proton sponges...

The potency of the inhibitors is affected by the pH. Changes in pH affect the protonation state of the guanidine. In conditions of low pH, such as in ischemia-reperfusion, some dtugs such as cariporide work more efficiently because they are on average more positively charged. 

The calculated 13C and 15N NMR chemical shifts, using the IGLO-HF and GIAO-MP2 methods, however, deviate substantially from the experimental results. This is in contrast with the previously reported results on protonated guanidines 113... 

The first step of an NOS catalyzed reaction is a classical P450-dependent N-hydroxylation of a guanidine, except for the involvement of H 4 B. As shown in Scheme 1.2, Fe(III)heme 1 first accepts one electron to give Fe(II)heme 2, which binds 02 to produce ferrous-dioxy heme 3. The second electron from H4B reduces 3 to peroxy-iron 4. Arg donates a proton to 4 to facilitate 0-0 bond cleavage to generate an oxo-iron (IV) cation radical species 5, which then rapidly hydroxylates the neutral guanidinium to NHA [4]. 

These authors conclude that the problem of internal solvation is still an experimental and theoretical challenge GB measurements for this type of molecules of low volatility are not always in good agreement194. Molecular orbital calculations may help to solve the difficult experimental problems, but they have to take into account conformational isomerisms and the prototropic tautomerisms of the amidine and guanidine moieties. In light of the above discussion, the proton affinities deduced from the experimental GB values should be based on accurate estimations of the entropy of cyclization 86. 

In negatively substituted guanidines [38], i.e., guanidines with an electron attracting substituent, there is little doubt that the substituent is carried on the imino-nitrogen, since the protons would... 

The guanidine function in compounds such as guanethidine is essentially completely protonated at physiological pH, and adrenergic neurone blockade is presumably caused by interactions of the cationic species at hypothetical... 

Several years later, Corey disclosed the C2 symmetric bicyclic guanidine 19 as an effective bifunctional catalyst for the Strecker reaction (Scheme 5.40) [74]. According to the catalytic cycle, HCN should hydrogen bond to the catalyst to form guanidinium-cyanide complex A. A subsequent increase in acidity of the catalyst N—H proton allows donation of a hydrogen bond to the aldimine to form TS assembly B. Enantiofacial attack of CN to the bound aldimine gives the Strecker product. 

Scheme 6.165 Enantioselective Strecker reactions catalyzed by biflinctional hydrogen-bonding guanidine organocatalyst 178. Catalytic action of 178 HCN hydrogen bonds to 178 and generates a guanidinium cyanide complex after protonation, which activates the aldimine through single hydrogen bonding and facilitates stereoselective cyanide attack and product formation.

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