Isomeric SMILES

Note that a single molecule may correspond to many different, but equivalent, SMILES strings. For example, for a given asymmetric molecule, starting from a different asymmetric atom will lead to a different, but equally valid, SMILES string. These various SMILES are called isomeric SMILES. They can be converted to a unique form called canonical SMILES (11). 

If any structures contain stereochemical atomic centers, consider using the isosmiles function instead of the cansmiles function. The isosmiles function and isomeric SMILES are discussed in a later section of this chapter. 

Exports of structural descriptors, SMILES and InChl, provide chemical structure information in a simple tab-delimited text file containing CID or SID and either the isomeric SMILES or InChl strings. Given the very nature of the formats of SMILES and InChl, not all chemical structure information can be identically represented. For example, SMILES encodes only covalent bonds, while PubChem supports the additional concepts of ionic, complex, and dative bonds. Most small molecules in PubChem can be reproducibly interconverted between InChl, SMILES, and PubChem ASN.l formats without loss of chemical structure information. 

The major hexa-CDD isomers were identified as 1,2,3,6,7>8 hexa--CDD one of the most toxic isomers, see Figure U. In addition 1,2,U,6,7,9- and 1,2,3,6,8,9-hexa-CDD or their Smiles-rearranged products (1,2,1, 6,8,9- an(i l,2,3,6,7,9 hexa-CDD, respectively), were found. These three isomers were always present in an almost constant isomeric ratio of 50 U0 10. Both of the hepta-CDD isomers were present in these samples in a ratio of 15 85 with the biologically most active (17) 1,2,3,, 6,7 hepta-CDD as the major constituent. All hexa-CDD isomers found in these samples were dimerization products of 2,3,, 6-tetrachlorophenol, the expected precursor of PCP in the chlorination starting from phenol (26). 

Traditional routes to phenoxazines include the thermolysis of 2-aminophenol and catechol, the latter acting as an acid catalyst, or catechol and ammonia. Phenothiazines are prepared similarly by heating diphenylamines with sulfur (Scheme 10) (B-78MI22701). 2-Hydroxy- (or mercapto-) 2, 4 -dini-trodiphenylamines cyclize to phenoxazines (or phenothiazines) in base by elimination of nitrous acid. This reaction is complicated by Smiles-type rearrangement so that mixtures of isomeric products are obtained (Scheme 11). 

Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase, dipyrido[2,3-/)]diazepinones, were prepared by J.R. Proudfoot and co-workers.These compounds are isomeric to the potent inhibitor nevirapine and available via the Smiles rearrangement of substrates that are intermediates used for the synthesis of nevarpine analogs. The deprotonated amide functionality in the rearrangement products displaces the chlorine at the 2-position to give the desired heterocycles in moderate to good yield. 

Isomerization of an S-cystelne conjugate to an -cysteine conjugate via the Smiles rearrangement has been observed In the metabolism of two trlazlne xenobiotics In higher plants atrazlne metabolism In sorghum (103,W ) 8 dlmethametryn metabolism In rice (J05). This nonenzymatic rearrangement (Equation 26) has not... 

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. 

When searching a database, if an isomeric query is used, only structures with the identical stereochemistry will be found using either a direct lookup or the matches function. If a nonchiral query is used, the direct lookup will find matching nonchiral structures, including canonical SMILES. When a nonchiral query is used in the matches function, structures of all chirality will be found. There is no one best method for dealing with a database containing many chiral molecules. It is important to carefully consider how to design and search such a database. 

The ratio between the isomeric phenoxazine products suggests that the main route of cyclization is a direct attack of the second nucleophilic center at the ortho-carbon atom of the aromatic ring an alternative route is a Smiles type rearrangement (70M9). Therefore, the following route of cyclization was proposed (Scheme 171). 

Constitutional isomerism is defined as that type of isomerism (i.e., different structures corresponding to the same molecular formula) resulting from differences in vicinity relationships between atoms. Examples of pairs of constitutional isomers are -butane and isobutane [CCCC versus CC(C)C in Smiles notation], ethanol and dimethyl ether (CCO versus COC), 1 - and 2-methylbutene (C=CCC versus CC=CC), and 1- and 2-propanol [CCCO versus CC(0)C]. Constitutional isomerism is adequately accounted for in chemical graph theory by the adjacency or distance matrices, which consider only the vicinity relationships. ... 

SMILES InChIKeyStd skeleton InChIKeyStd isomerism InChIKeyStd charge... 

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