Thiamin, structure thiazolium ring

Thiamin, structure of, 530, 1045 thiazolium ring in, 530 Thiamin diphosphate, p/Ca of, 1151 reaction with pyruvate, 1151-1153 structure of. 1151 ylide from. 1151 Thiazole, basicity of. 948 thio-, thioester name ending, 787 Thioacetal, synthesis of, 743 Thioanisole, electrostatic potential map of. 777... 

I have been pursuing enzyme mimics, artificial enzymes that perform biomimetic chemistry, since starting my independent career in 1956. In the first work [52-59] my co-workers and I studied models for the function of thiamine pyrophosphate 1 as a coenzyme in enzymes such as carboxylase. We discovered the mechanism by which it acts, by forming an anion 2 that we also described as a stabilized carbene, one of its resonance forms. We examined the related anions from imidazolium cations and oxazolium cations, which produce anions 3 and 4 that can also be described as nucleophilic carbenes. We were able to explain the structure-activity relationships in this series, and the reasons why the thiazolium ring is best suited to act as a biological... 

However, another study was an example of nature appreciation—the structure of thiamine was varied to learn what was special about the particular thiazolium derivative that was natural thiamine (11). As a chemical catalyst—ignoring the question of what effect changes would have on the ability of the coenzyme to bind to the proteins that have evolved to use it—thiamine proved to be the optimal relative to other related structures because of a balance of catalytic ability and chemical stability. The anion 4 derived from an imidazolium ring instead of a thiazolium ring was a weaker catalyst but was more stable in water (10). [The imidazolium aiuon and its dihydro derivative have proven to be very useful metal ion ligands, including... 

Only oxazole, of the trio, does not play any part in normal biochemical processes, though there are secondary metabolites (especially from marine organisms) which incorporate thiazole (and oxazole) units - the antibiotic cystothiazole A, from the myxobacterium Cyctobacter fuscus is an example. Imidazole occurs in the essential amino acid histidine histidines within enzymes are intimately involved in catalysis requiring proton transfers. The structurally related hormone, histamine, is a vasodilator and a major factor in allergic reactions such as hay fever. The thiazolium ring is the chemically active centre in the coenzyme derived from thiamin (vitamin B,). 

Our earliest studies concerned the mechanism by which thiamine pyrophosphate (1) acts as a coenzyme (Fig. 1.1). We discovered that the C-2 hydrogen on the thiazolium ring of thiamine was able to ionize to form a thiazolium ylide (2) that has the important resonance structure (3), which can be called a stabilized carbene . We pointed out this carbene contribution to its structure, related to the well-known hybrid structure of carbon monoxide, and also saw that an imidazolium ion (4) and an oxazoKum ion (5) could form such yhde/carbene resonance structures. Recently such structures, usually referred to as stabilized carbenes , have proven to be useful ligands for catalytic metal ions. The carbenes are of course stabilized by electron donation from the heteroatoms, forming the ylide resonance forms. 

To explain this behavior, we have to examine its structure more carefully. The coenzyme thiamine pyrophosphate (thiamine-PP) contains a thiazolium ring system ... 

One of the remarkable facets of thiamine chemistry is that the thiazolium ring forms a covalent intermediate with the substrate and can act either as an electrophile or a nucleophile. It is thus a catalyst with dual functionality. In other words, the electron flow can occur from the bond to be broken into the structure of the coenzyme (toward the =N — group) and then back toward... 

There are also two known strucmres of cadmium complexes with 2-(a-hydroxybenzyl)thiamine (HBthiamine), an intermediate in thiamine catalysis with the a-hydroxybenzyl substituent in the C(2) position of the thiazolium ring. The complexes [Cd(HBthiamine)X3] (X = Cl or Br) are isotypic, with a structure similar to that of [Cd(thiamine)Cl3] [Cd-N = 2.251(3) A and 2.257(9) A]. In these structures the conformation of the thiamine skeleton is S (tp-p = 97 and -97°,... 

Thiamin was isolated in 1926 from rice bran by Jansen and Donald [338]. Its structure, consisting of a pyrimidine ring (4-amino-2-methyl-5-pyrimidyl) and a thi-azole ring (5-(2-hydroxyethyl)-4-methyl-thiazolium) joined by a methylene bridge, was first elucidated by Williams et al. [339],... 

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