SMILES Notations

The SMILES notation is a means by which certain chemical structures can be described using a series of simple letters and numbers expressed in linear fashion, even for complex cyclic structures. This approach is particularly useful as input for computer models when chemical names and CASRN are unknown. As mentioned above, SMILES is an important tool in hazard and exposure modeling used in EPA s voluntary Sustainable Futures Program [1]. It can also be used to identify substances under REACH, and examples are shown in the nomenclature Technical Guidance Document (TGD) along with molecular and structural formulas. 

There are a few basic principles key to understanding the language of SMILES, but it should not be assumed that understanding SMILES is a relatively simple matter, even for an experienced chemist. Much practice and usage of the system is needed to use SMILES independently, but it is helpful to understand the basics listed below. 

Atoms are represented by single letters just as they are in the Periodic Table C is carbon, O is oxygen, and N is nitrogen. 

Hydrogen atoms are not included in the representation. Eor example, C with no other connecting atoms is methane C-C is ethane and so on. 

Bonds single bonds are represented by a simple dash (-), double bonds by an equal sign, and triple bonds by the symbol. Thus, C=C is ethylene C C is acetylene and hydrogen cyanide IS C N. 

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SLN is easy to learn and its use is intuitive. The language uses only six basic components to specify chemical structures. Four of them are hsted in Table 2-3 and can be compared directly with the SMILES notation of Section 2,3.3. 

Stereochemistry can also be expressed in the SMILES notation [113]. Depending on the clockwise or anti-clockwise ordering of the atoms, the stereocenter is specified in the SMILES code with or respectively Figure 2-78). The atoms around this stereocenter are then assigned by the sequence of the atom symbols following the identifier or (g). This means that, reading the SMILES code from the left, the three atoms behind the identifiers ( ) or ( )( )) describe the stereochemistry of the stereocenter. The sequence of these three atoms is dependent only on the order of writing, and independent of the priorities of the atoms. 

Figure 2-78. The stereochemistry of (2R,3 ,5 )-2-hydroxy-3,5-heptadiene nitrile can be expressed in the SMILES notation with or (back)slashes.

An alternative way to represent molecules is to use a linear notation. A linear notation uses alphanumeric characters to code the molecular structure. These have the advantage of being much more compact than the connection table and so can be particularly useful for transmif-ting information about large numbers of molecules. The most famous of the early line notations is the Wiswesser line notation [Wiswesser 1954] the-SMILES notation is a more recent example that is increasingly popular [Weininger 1988]. To construct the Wiswesser... 

The solubility is expressed as logarithm of molar fractions log(S). A recommended partition of the data into training and test sets is also taken from the mentioned paper. Six outliers described in Huanxiang et al. (2005) were removed from the considerations. SMILES notations of organic solvents for this study have been obtained with ACD/ChemSketch software (http //www.acdlabs.com/) according to CAS numbers from US National Library of Medicine (http //toxnet.nlm.nih.gov/). 

Weininger D, Weininger A, Weininger L (1989) SMILES. 2. Algorithm for generation of unique SMILES notation, J. Chem. Inf. Comput. Sci. 29 97-101. 

The Simplified Molecular Input Line Entry System (SMILES) is frequently used for computer-aided evaluation of molecular structures [1-3]. SMILES is widely accepted and computationally efficient because SMILES uses atomic symbols and a set of intuitive rules. Before presenting examples, the basic rules needed to enter molecular structures as SMILES notation are given. 

Linear Notation A SMILES notation is a string consisting of alphanumeric and certain punctuation characters. The notation terminates at the first space encountered while reading sequentially from left to right. 

In most cases there is more than one way to write the SMILES notation for a given compound. For example, pyridine can be entered in six different but correct ways ... 

To obtain a unique SMILES notation, computer programs such as the Toolkit include the CANGEN algorithm [1] which performs CANonicalization, resulting in unique enumeration of atoms, and then GENerates the unique SMILES notation for the canonical structure. In the case of pyridine, this is notation (III). Any molecular structure entered in the Toolkit is converted automatically into its unique representation. 

Convenience of entering structures can be a matter of importance to the user, but this is often a matter of personal preference and should be checked out carefully in advance. Some users will require batch entry of large files of structures. Both KOWWIN and CLOGP use the SMILES notation (Weininger, 1988, 1989) as the primary entry medium, accepting SMILES files directly or providing conversion from other popular notations. Both accept CAS numbers. CLOGP also accepts compound names and synonyms e.g., AZT or zidovudine. 

For users who prefer to draw in new structures, the later versions of Chem Draw will deliver a SMILES notation which can be used via cut and paste commands, and ISIS Draw delivers a MOLfile which can be automatically converted to a SMILES file. ACD / LogP uses a proprietary drawing program, MolDraw, which is easy to learn and use. Entry by name in ACD is accomplished via a Dictionary with about 48,000 entries. Drawn structures can be saved to a file, but in version beta 0.9 of ACD/LogP there is no method of batch entry from either SMILES files or MDL MOLfiles. 

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. 

The octanol-water partition coefficient (Kow), characterizing distribution of a non-ionized compound between an octanol (o) and an immiscible aqueous (w) layer, may function as a measure of lipophilicity, that is often listed as its logarithmic value (log P). Therefore, log P may be used as a predictor of extractability in LLE. Table 1 presents log P values of TA calculated by the Molinspiration software [25] using SMILES notation for chemical structures. The SMILES concept is addressed in the next section [26], Conformity of calculated (calc.) and experimental (exp.) log P values is satisfying, as exemplarily shown for atropine (1.83 exp. [27] 1.77 calc.) and scopolamine (0.98 exp. [22] 1.05 calc.). 

The same modeling scheme has been employed by Toropov et al. [72], who once again used the DCW descriptor. But, in this case, the descriptor denoted the variance in a set of 26 organic solvents coded with the SMILES notation. The model was externally validated, which confirmed its predictivity. The values of... 

Thor (a database system based on Daylight s SMILES notation) Daylight Chemical Information Systems, Inc. 123 http //www.daylight.com/... 

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