Acid-base chemistry hydrogen bond donor

The range of functionality provided by the 20 amino acids found in proteins consists of weak acids and bases, nucleophiles, hydrogen bond donors and acceptors, and the redox active thiol/disulfide. This limited range of chemistry is inadequate for the catalysis of many reactions found to occur in biological systems. Therefore, a variety of small organic molecules, called cofactors, coenzymes, or vitamins, have evolved to broaden the limited range of chemistry that can be catalyzed by simple proteins. 

Quantum chemical computations of H complexes heats formation in case of interaction of large organic molecules lead to high errors. A more perspective way is the use of well known relations of physical organic chemistry for this purpose. These equations allow to predict the heats of hydrogen-bonded or donor-acceptor complexes formation on the basis of donor (base) and acceptor (acid) empirical parameters. There are Drago and Weyland s equation [71]... 

Recently, Lazo and co-workers reported a combinatorial library of PTPIB inhibitors based on a pharmacophore derived from the structure-activity relationships for several natural product inhibitors of PSTPases such as oka-daic acid, microcystins and calyculin A [425, 426], The pharmacophore model involved a carboxylate, a non polar aromatic group and hydrogen-bond acceptors and donors and was used as a platform for functional group variation. Among the 18 library compounds generated by parallel solid-phase chemistry, a non-competitive inhibitor for PTPIB was identified (library 41, Kj=0.85 jiM) [425] and as well a serine/threonine phosphatase inhibitor (library 42, IC50 < 100 /iM) [426],... 

In case of the hydrogen bond formation, the proton is not stably positioned at either the base B or the conjugated base A . In other words, the donor and acceptor cannot always be distinguished. From a chemistry point of view, however, a hydrogen bond can be understood as an incipient proton transfer reaction from a proton dmior acid (HA) to a proton acceptor base (B). fri this context, the proton transfer and hydrogen IxMid formation, either in the A- H B or ionic A - H—B" form, are well correlated with the pATa values of the acidic and basic components. 

Michael condensations, together with the Diels-Alder cycloaddition and the aldol reactions, are the most powerful and useful bond-fonning reactions in synthetic organic chemistry. Like the nitro-aldol (Henry) additions, nitroalkanes are particularly appropriate reagents in Michael reactions they act as a-hydrogen donors. Nitroalkanes react easily with typical Michael acceptors such as a,p-unsaturated aldehydes or ketones under base or Lewis acid catalysis. ... 

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