Database, CHIRBASE

CHIRBASE Database Current Status and Derived Research Applications using Molecular Similarity, Decision Tree and 3D Enantiophore Search... 

The need for an overall and combined chemical structure and data search system became clear to us some time ago, and resulted in the decision to build CHIRBASE, a molecular-oriented factual database. The concept utilized in this database approach is related to the importance of molecular interactions in chiral recognition mechanisms. Solely a chemical information system permits the recognition of the molecular key fingerprints given by the new compound among thousands of fingerprints of known compounds available in a database. 

In this chapter, we will discuss the present status of CHIRBASE and describe the various ways in which two (2D) or three-dimensional (3D) chemical structure queries can be built and submitted to the searching system. In particular, the ability of this information system to locate and display neighboring compounds in which specified molecular fragments or partial structures are attached is one of the most important features because this is precisely the type of query that chemists are inclined to express and interpret the answers. Another aspect of the project has been concerned with the interdisciplinary use of CHIRBASE. We have attempted to produce a series of interactive tools that are designed to help the specialists or novices from different fields who have no particular expertise in chiral chromatography or in searching a chemical database. 

Some details of the database are available on the Web [6] and consist today of about 61 000 different chiral separations (Table 4-1). Between 12 000 and 15 000 new separations are stored continuously each year in CHIRBASE. 

ISIS databases are hierarchical, so CHIRBASE was designed to incorporate about 60 data fields on several levels of detail (the main fields are listed in Table 4-2). The first level contains the molecular structure of the sample combined to the molecular structure of the CSP, producing a unique location or entry for a specific sample-CSP couple. Consequently, in the current version of CHIRBASE, which contains 40 000 entries, one entry corresponds to the separation of one sample on one CSP and contains in different sublevels a compilation of all the references and the various analytical conditions available for this separation. 

If some fields may be empty in the sublevels, all the fields in the main level are required for each entry. A new chiral separation record can be added in CHIRBASE solely if the authors correctly identify both sample and CSP. Since the beginning of the project, our policy has been to contact the authors of all publications containing incomplete, ambiguous or inconsistent data and to ask for additional information. Providing the separations with unique case numbers helps us considerably in this essential task, and also facilitates avoiding redundancies in the database. When chiral separations are reported for the second time in a new publication with exactly the same chromatographic conditions, this is stated in a footnote added in the field comments . In this field, miscellaneous information that cannot appear elsewhere are listed (detection limit, description of a reported chromatogram, racemization study, mobile phase limitations, etc.). 

In addition to addressing the practicalities of database maintenance, we also aim to enhance the range of the facilities available, to make the information within CHIRBASE more readily accessible to users. CHIRBASE contains two form-based applications for query building designed to help novice or expert users to formulate queries the query menu and the automatic search tool. 

CHIRBASE provides integrated responses from single questions, as well as from combinatorial questions constructed on the basis of any specific query corresponding to one or several field(s) occurring in the database. With the molecular structure of a sample in hand, the search can be conducted interactively from the query menu form. 

From these preliminary results, we can assume that such enantiophore queries could be used to search in a database of compounds with unknown enantioselectiv-ities. With respect to the percentage of resolved samples that are retrieved in CHIRBASE, the resulting list should contain a similar yield of compounds providing favorable specific interactions with the CSP receptor binding sites. 

Nonetheless, these results are partial and can be seen only as a test study, and clearly many improvements will be considered. For example, the decision at each node should not be restricted to the only use of molecular key attributes, but should also take into account the mobile phase constituents. Future works will also extend this approach to the full database and will probably lead to the introduction of knowledge rules in CHIRBASE. Knowledge rules will help the users not only in the choice of a wide range of columns but also in the selection of appropriate experimental conditions. 

CHIRBASE Database Current Status and Derived Research... 

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