SMILES fragments

In this chapter, the genesis of SMILES-based descriptors (as well as perspectives of utilization of these characteristics for QSPR/QSAR analyses) is discussed. We concluded that in fact the SMILES-based optimal descriptors are derivatives of the graph-based optimal descriptors. In fact the SMILES-based descriptors are calculated with scheme that is similar to the well-known additive scheme (Zinkevich et al., 2004), but instead of contributions for the molecular fragments (chemical elements, different kinds of cycles, covalent bonds, etc.) contributions for the SMILES fragments (c, C, n, N, Cl, Br, =,, etc.) are using. 

A tremendous number of various fragments are used in structure-property studies atoms, bonds, topological torsions , chains, cycles, atom- and bond-centered fragments, maximum common substructures, line notation (WLN and SMILES) fragments, atom pairs and topological multiplets, substituents and molecular frameworks, basic subgraphs, etc. Their detailed description is given below. 

WEN and SMILES fragments correspond respectively to substrings of the Wiswesser Line Notation or Simplified Molecular Input Line Entry System strings used for encoding the chemical structures. Since simple... 

Green, F.M., Dell, E.J., Gilmore, I.S., Seah, M.P. (2008) Identification of complex molecules at surfaces G-SIMS and SMILES fragmentation pathways. Int. J. Mass Spectrom., 272,38-47. 

A Smiles rearrangement (equation 28) was also responsible for the secondary loss of SOz in the El induced fragmentation of 2-(p-chlorophenoxymethyl)-3-arylsulfonylmethyl-5-chlorobenzo(h)thiophenes (59) but not in their 3-alkylsulfonylmethyl derivatives33. In the latter, the loss of RS02 from the molecular ions and those of RS02 and RSOH from the [M — C1C6H40] + ions are the predominant routes of fragmentation. 

Substmcture search of this backbone (smiles O = C(N(C)C1C)CN(C)C1=0) reveals several hundreds commercially available compounds, which likely have been synthesized by the above synthetic route [1]. This backbone can also be considered as a peptide mimetic by using a-amino acid derived isocyanide and amine components and will be of value for biological studies and for the discovery of hydrolysis resistant and biologically active peptide fragments (Fig. 6). 

The method Meylan et al. (1992) described also has been encoded in a computer program, PCKOCWIN. After the user enters the structure of the chemical of interest represented in SMILES notation (Anderson et al., 1987 Weininger, 1988), the program automatically calculates y and determines the appropriate fragments and correction factors. 

In addition to physical properties, substructure-based filters can be applied to reduce further the number of molecules, for instance molecules with undesirable functionality for example, reactive or toxic groups can be removed and molecules with particular features (or atoms) can be actively selected. There may be particular functionality that it is desirable to avoid due to assay format, such as fluorophores in fluorescence-based approaches. Structural features for these inclusion and exclusion criteria can be readily formulated using SMILES-based procedures and this type of substructure-based compound selection technique can also be employed in the generation of focused sets of fragment molecules. 

Another reaction to yield unsymmetrically substituted 1,2,4,5-tetrazines is that of sodium ethoxide in ethanol with S-( 1 -aryl-1 7/-tetrazol-5-y 1) lV-(/Miitrophenyl)benzothiohydrazonates (11). The mechanism of the reaction is complex and seems to involve a competitive Smiles rearrangement, fragmentation and dimerisation (Scheme 7) [95JCR(S)224],... 

The software program SMILOGP for the calculation of logP is based on the Broto-Moreau-Vandycke hydrophobic constants and the SMILES notation for the recognition of molecule atom-centred fragments [Convard etal, 1994]. 

A descriptor center finally consists of a structural part (e.g., atom, multiple similar atoms, pseudoatoms, fragments) and a property. To define this structural part efficiently, the line notation SLang is used, which is similar to simplified molecular input line enky specification (SMILES) and SMILES arbitrary target specification (SMARTS) [12]. Examples for structural parts and their representations in SLang are as follows ... 

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