Tautomer algorithm

Physicochemical properties rather than reactivities were also explored. Molecular electrostatic potential (MEP) was calculated for the [l,2,4]triazolo[4,3- ]pyridine fragment 23, according to the CHELPG algorithm. This afforded a prediction of its H-bond acceptor ability in view of the synthesis of p38 MAP kinase inhibitors <2005JME5728>. Tautomerism was also examined for compound 24, also postulated as two possible acyclic structures. The ab initio self-consistent field (SCF)-calculated energies support 24a as the most stable tautomer <1999MRC493>. 

The program is reported to carry out simple Hiickel molecular orbital calculations to determine the relative sensitivity of aromatic carbon atoms to oxidation and the relative stability of keto and enol tautomers. Klopman et al. (1999) have reported that for polycyclic aromatic hydrocarbons, adequate reactivity is an essential but not sufficient condition for enzyme catalyzed reaction. The accessibility of the reactive site (i.e., the absence of steric hindrance) was also found to be important. Genetic algorithms have been used to optimize the performance of the biotransformation dictionary by treating the initial priority scores set by expert assessment as adjustable parameters (Klopman et al., 1997). 

Finally, there are algorithms available for simply recognizing when two structures are tautomers. This is sufficient to locate all isomers in a database. In general, two structures are considered to be structural isomers if they share the same molecular formula. Tautomers are a special type of structural isomer in which the connectivity of the atoms, as well as the molecular formula, is the same. For example, butane (smiles CCCC) and isobutane (smiles CC(C)C) are strucural isomers but not tautomers. Butyraldehyde (smiles CCCC=0) and but-l-en-l-ol (smiles CCC=CO) are structural isomers as well as tautomers. A direct comparison of the molecular formulae readily shows the structural isomerism. There is a text graph representation that can allow easy detection of tautomers. 

For tautomers, the ideal situation is to store one preferred tautomeric form and register other forms as synonyms of this preferred one. However, there is no universally accepted algorithm for tautomer generation, and each registration system will have its own implementation. There will be cases where the system perceives two structures to be tautomers but the chemist knows better and wants to store them separately. Conversely, due to limitations in the tautomer perception algorithm, two tautomeric forms may not be recognised as such. A practical registration system must therefore allow chemists to override the system-provided default. 

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