SMILES code

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. 

A SMILES code [22], MDL Molfile [50], or JME s own compact format (one-line representation of a molecule or reaction including the 2D coordinates) of created molecules may be generated. The created SMILES is independent of the way the molecule was drawn (unique SMILES see Section 2.3.3). Extensions to JME developed in cooperation with H. Rzepa and P. Murray-Rust also allow output of molecules in the CML format [60]. 

Convard, T., Dubost,). P., Le Solleu, H., Kummer, E. SmilogP a program for a fast evaluation of theoretical log P from the Smiles code of a molecule. Quant. Struct.-Act. Relat. 1994, 13, 34-37. 

Tab. 17.1. Smiles codes and names of the test set compounds used in Caco-2 external permeability prediction...

Fig. 11.17. Search for bioisosteres of propionic acid based on

Table 1 Log P and SMILES code of tropane alkaloids used in LC-MS-based analysis...

SMILES provides an-easy-to-handle-format useful for entries in any software application. Therefore, based on the SMILES code pKb and log P values can be predicted beneath other chemical and biological properties (Table 1). 

Figure 2.3 gives the structure, WLN, and SMILES codes for a sample chemical. It is apparent that the WLN code is more complicated and much less obvious to a chemist than the SMILES code. The numbers refer to the atom numbers used in developing the WLN code. 

The presence of a branch in the structure raises the question of where to start coding. With the SMILES system it does not matter where one starts. A SMILES interpreter will produce the same structure from any valid SMILES coding for a compound. In some circumstances, such as the system s use in databases, it is necessary to have a unique SMILES string for a molecule. Using a set of rules it is possible to uniquify a SMILES string. 

It is this writer s firm conviction, that the invention of the SMILES code and its convertibility with computer-readable SDF format has opened the door to great steps forward in man s ability to understand structure-activity relationships. Despite the present differences between the two major SMILES code interpreting software environments, I recommend that all students of chemistry become familiar with this code. 

Log KoW, MP, and Kp values were calculated with the Syracuse Research Corporation (SRC, Syracuse, NY) KOWWIN, MPBPWIN, and DERMWIN software packages (SRC, Syracuse, NY, USA), respectively, using the SMILES codes of the chemicals as the input. Values of MW and ST were calculated with the Advanced Chemistry Development (ACD) ChemSketch software. 

For small molecules the system should allow one to construct the molecule and generate a reasonable three-dimensional conformation quickly. The best currently available approach is CONCORD (27), which rapidly (15-30s) generates a low-energy conformation for most classes of organic compounds from a simple alphanumeric SMILES code (28), a powerful, easily learned... 

Only a few compounds screened in early lead identification phases are synthesized in-house. More flexible and cost effective is to purchase chemicals from external suppliers. Most vendors provide lists of some ten to himdred thousand chemicals on compact discs and guarantee delivery within days to weeks. To explore this huge amount of data with the aid of computers, chemical information is transformed to computer-readable strings, e.g., smiles code, and different descriptors are determined. 1-dimensional (1-D) descriptors encode chemical composition and physicochemical properties, e.g., molecular weight, stoichiometry (C O Hj,), hydrophobicity, etc. 2-D descriptors reflect chemical topology, e.g., connectivity indices, degree of branching, number of aromatic bonds, etc. 3-D descriptors consider 3-D shape, volume or surface area. 

Figure 6 Generation of the SMILES code of morphine (reproduced from Figure 6 of ref. [256] with permission from Pergamon Press Ltd., Headington Hill Hall, Oxford 0X3 OBW, UK).

Table 7. Log P calculation of chlorpromazine (4) by the program CLOGP [253]. Input of the structure in SMILES code cl2cc(Cl)ccc2Sc3ccccc3NlCCCN(C)C unique SMILES code, generated by the program CN(C)CCCN2cIccccclSc3ccc(Cl)cc23 (reproduced from ref. [253] with permission...

SmilogP A Program for a Fast Evaluation of Theoretical LogP from the Smiles Code of a Molecule. 

META takes advantage of the GUI (graphic user interface) technology and implements both graphic input and output along with traditional input such as SMILES code," KLN code," MOL file, and output such as text files. Figures 2 and 3 show the basic screens of META. Not having access to the other expert systems leaves us to conjecture about their user interface. We suspect that they also provide a choice of user friendly ways to input data and display results. 

Cis/trans stereoisomerism is expressed using directional single bond symbols, namely / and instead of the (usually omitted) character. They are interpreted as the bond is pointing up or down , respectively. Molecule 22, for example, can be SMILES-coded as C/C=C/C(=0)0 . Refer to the Web documentation for further details. ... 

Obtain SMILES codes for all of the compounds to be included in the PCA (see Notes 1 and 2). SMILES codes for known compounds can be obtained from PubChem (http //pubchem. ncbi.nlm.nih.gov/) or other online resources. For new compounds, SMILES codes can be generated using ChemBioDraw see Note 3). 

Create a new MS Excel file containing one column for compound names (Column A) and one column for SMILES codes (Column B) (ret Note 4). Do not include a header row. Group the compounds by compound class (such as Drugs, Natural Products). Save the MS Excel file as a Text (tab delimited) (.txt) file that will be used in Subheading 3.1, step 4. Delete the compound names column and save an additional. txt file that contains only SMILES codes, which will be used later will be used later for batch processing (Subheading 3.1, step 7). 

Fig. 3 Uploading SMILES codes to calculate ALOGpS and ALOGPs at the VCC Lab Website...

---