Imidazole group

Histidine is one of the 20 naturally occurring amino acids commonly found in proteins (see Chapter 4). It possesses as part of its structure an imidazole group, a five-membered heterocyclic ring possessing two nitrogen atoms. The pAl for dissociation of the imidazole hydrogen of histidine is 6.04. 

FIGURE 21.18 (a) The Cn site of cytochrome oxidase. Copper ligands inclnde two histidine imidazole groups and two cysteine side chains from the protein, (b) The coordination of histidine imidazole ligands to the iron atom in the heme a center of cytochrome oxidase. 

The antiarrhythmic activity of local anesthetics has been noted several times previously. Another such agent is prepared by first alkylating isopropylamine with sulfone 199. Reaction of the ])ioduct (200) with diethylethylenediamine and carbonyldiimidazole results in transfer of the CDI carbonyl group and formation of the urea suricainide (201) [52]. The transform in all likelihood involves stepwise replacement of the imidazole groups by the basic groups in the other reactants. 

Murakami et al. reported that a cyclophane 27 having two imidazole groups is activated by Cu2+ ions in the hydrolysis of p-nitrophenyl dodecanoate 25,26), although the activation seemed to be small. 

Cationic polyelectrolytes containing imidazole groups have been investigated by some researchers. Morawetz et alU4 first found that a cationic polymer, poly (l-vinyl-3-ethylimidazolium iodide), 65 (PQMelm), enhanced the hydrolyses of the negatively charged esters, i. e. NABA and 4-acetoxy-3-nitrobenzenesulfonate 66 (NABS). At intermediate pH, a large catalytic effect was observed and this was... 

Klotz etal.U9, l2° asserted that polymers from polyethylenimine reacted with chloromethylimidazole and dodecyliodide were excellent models for hydrolase. 70 [PEI-D(10%)-Im(l 5%)] catalyzed the hydrolyses of PNPA 270 times faster than imidazole itself. The authors also found that lauroylated polyethylenimine containing hydroxamate and imidazole groups, 71 [PEI-HA(8%)-L(8%)-Im(6.6%)], had a high efficiency in hydrolyses, i. e. 310 times that of imidazole. 

Concurrent with these investigations, polyphosphazene matrices, functionalized with aminoacid esters or with imidazole groups, became of importance because of their tissue engineering aspects in bone regeneration [655,656,679], treatment of periodontal diseases [657], and nerve reconstruction problems [680-682] in which the remarkable bio compatibility of POP matrices was coupled with their tuneable bio degradability. 

All amino acids possess at least two weakly acidic functional groups, R—and R—COOH. Many also possess additional weakly acidic functional groups such as —OH, —SH, guanidino, or imidazole groups. 

A silica gel containing 3-imidazole propyl groups bonded to surface atoms of silicon has been prepared (253), and was treated 254) with a solution of Fe(TPP)L2, where L = py or pip, where upon the iron(II) porphyrin became attached to the imidazole groups on the surface of the gel,... 

The nitrogen donor commonly found coordinated to metal ions in biology is the imidazole group from histidine. It is found coordinated... 

X-ray diffraction studies on several forms of the enzyme have demonstrated that the active site is composed of a pseudo-tetrahedral zinc center coordinated to three histidine imidazole groups and either a water molecule [(His)3Zn-OH2]2+ (His = histidine), or a hydroxide anion [(His)3Zn-OH] +, depending upon pH (156,157). On the basis of mechanistic studies, a number of details of the catalytic cycle for carbonic anhydrase have been elucidated, as summarized in Scheme 22... 

In contrast to the lability of certain dN adducts formed by the BHT metabolite above, amino acid and protein adducts formed by this metabolite were relatively stable.28,29 The thiol of cysteine reacted most rapidly in accord with its nucleophilic strength and was followed in reactivity by the a-amine common to all amino acids. This type of amine even reacted preferentially over the e-amine of lysine.28 In proteins, however, the e-amine of lysine and thiol of cysteine dominate reaction since the vast majority of a-amino groups are involved in peptide bonds. Other nucleophilic side chains such as the carboxylate of aspartate and glutamate and the imidazole of histidine may react as well, but their adducts are likely to be too labile to detect as suggested by the relative stability of QMs and the leaving group ability of the carboxylate and imidazole groups (see Section 9.2.3). 

Substitution of a protonated imidazole group by an azide anion permits an azido-carboxylic ester to be obtained in good yield [137]... 

In a similar way, iV-bromination on the imidazole group of an imidazolide by N-bromosuccinimide increases the compound s reactivity E11],[140]... 

In the reaction of a phosphoric ester diimidazolide (for preparation see Section 2.2) with an alcohol it is possible to substitute either one or two of the imidazole groups. 

In the reaction of heptafluorobutyrylimidazole with a carboxylic acid such as 2-ethylhexanoic acid, the imidazole group is exchanged quantitatively. 

From the standpoint of modeling Type I copper proteins,4,5,59,60 a variety of imidazole-based ligands containing thioether sulfurs and imidazole groups have been synthesized.61,62 The structures and spectroscopic properties of their copper(II) complexes (51)-(53) and (55)-(60) were investigated.65,79-82 To characterize apical copper(II)-thioether bonding, the complex (51) was... 

The crystal structure of the C-functionalized imidazole derivative of 1,5,9-triazcyclododecane (75) shows a five-coordinate zinc with four /V-donors from ligand and chloride in a distorted trigonal bipyramidal arrangement. The Zn—N imidazole bonds are the shortest at 2.025(3) A.678 Deprotonation of the imidazole group resulted in a bridging imidazolate to form dinuclear zinc complexes. The pATa of 10.3 varies from the pATa of bound water with similar ligands (as low as 7.3) and the complex is not catalytic for the hydrolysis of esters. 

Histidine, an amino-acid with an imidazole group in its side-chain, reacts with PtCll- slowly even in KOH and over some days (54). It gives the complex... 

Sapse et al.41b performed ab initio calculations on benzene-benzene as a model for the interaction between the a phenylalanine residue and the benzoyl portion of a typical folate compound. In addition, that study examined the complex formed hy a benzene ring and a polar serine which acts as a hydrogen donor, between a benzene ring and the amino group of a meta diamino-imidazole group (present in some anti-folates) and between serine as a hydrogen donor and the diamino-imidazole group as the electron donor. 

Fds with conventional [Fe2-S2] clusters can undergo a one-electron transfer to a deeply valence-trapped FemFen species. For proteins of known structure (and presumably others) one iron atom is closer to the surface (by about 0.5 nm) and it has been established that the added electron resides on that atom. No instances are known where an [Fe2-S2] centre acts as a physiological two-electron donor or acceptor. In addition to the conventional [Fe2-S2] ferredoxins, the electron-transfer chains of mitochondria and photosynthetic bacteria contain Rieske proteins which have a cluster with the composition [(Cys.S)2FeS2Fe(N.His)2], in which the two imidazole groups are bound to the same iron atom (Figure 2.9). This atom is the site... 

The most effective catalyst for the hydrolysis of p-nitrophenyl acetate was reported to be a cycloheptaamylose derivative containing approximately two imidazole groups per cycloheptaamylose molecule (Cramer and Mackensen, 1970). At pH 7.5 and 23°, this material accelerates the rate of release of phenol from p-nitrophenyl acetate by a factor of 300 when compared with the hydrolysis of this substrate in the absence of catalyst. However, when compared with an equivalent concentration of imidazole, which is an effective catalyst for ester hydrolysis at neutral pHs, the rate accelerations imposed by this cycloheptaamylose derivative are only two- to threefold. Cramer and Mackensen attributed this rate enhancement to nucleophilic displacement of phenol from the included ester by a cycloheptaamylose hydroxyl group, assisted internally by the attached imidazole group... 

There are some side reactions that may occur when using EDC with proteins. In addition to reacting with carboxylates, EDC itself can form a stable complex with exposed sulfhydryl groups (Carraway and Triplett, 1970). Tyrosine residues can react with EDC, most likely through the phe-nolate ionized form of its side chain (Carraway and Koshland, 1968). The imidazolyl group of histidine may react with sulfo-NHS esters, resulting in an active carbonyl imidazole group which subsequently hydrolyzes (Cuatrecasas and Parikh, 1972). Finally, EDC may promote unwanted polymerization due to the usual abundance of both amines and carboxylates on protein molecules. 

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