- Qualitative Analysis of Organic Compounds.
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- Organic Functional Group Analysis: Theory and Development
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- Organic Chemistry Notes and Cheat Sheets
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Search HathiTrust. Tools Cite this Export citation file. Similar Items Quantitative organic analysis via functional groups. Author Siggia, Sidney. Published An introduction to modern organic analysis Author Siggia, Sidney. Organic functional group analysis by micro and semimicro methods Author Cheronis, Nicholas Dimitrius, Organic functional group analysis.
Author Critchfield, F E Published Organic functional group analysis; theory and development, Author Schenk, George H. Tsu Sheng , Published We do not claim that this algorithm provides an ultimate definition of FGs. Every medicinal chemist has probably a slightly different understanding about what a FG is. In particular the definition of activated sp3 carbons may create some discussion.
In the present algorithm we restricted our definition only to classical acetal, thioacetal or aminal centers i. Extension of FGs also to alpha-substituted carbonyls i. Since our major interest was in comparing various molecular datasets and not in reactivity estimation we implemented this strict definition of acetal carbons. To assess the possible reactivity of molecules, various substructures filters are available, as for example already mentioned PAINS [ 9 ] or Eli Lilly rules [ 10 ]. To illustrate better the algorithm some examples of FGs identified for few simple molecules are shown in Fig.https://reicrusorletsubs.ga
Qualitative Analysis of Organic Compounds.
Example of functional groups identified. Groups are color coded according to their type. FGs, particularly those with several connection points, may be present in numerous forms differing by variation in their environment. The attachment points may be unsubstituted i. A simple amide group with 3 connection points may form 18 such variations two connections on nitrogen are considered to be symmetrical here. As another example list of 20 ureas with different environments extracted from the ChEMBL database vide infra is shown on Fig.
For the more complex groups the number of possible variations is even considerably larger.
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Various forms of the urea functionality differing in the environment patterns. The numbers in the corner indicate the number of molecules in ChEMBL in which this particular group is present and the percentage. In most cases, however, it is not necessary to go into such level of detail. When studying frequency statistics of FGs in chemical databases one is usually interested in percentage of molecules with, say, urea or sulfonamide functionalities and not in the environment details. One needs to be careful here, however. In some special cases, particularly for smaller FGs the differences in the environment are very important, for example to distinguish between alcohols and phenols or amines and anilines.
To consider these different scenarios the generalization scheme described below was developed:. FGs with just single central N or S atom are not replaced, this allows to distinguish secondary and tertiary amines, and thiols and sulfides. This scheme provides a good balance between preserving sufficient, chemically meaningful details on one side and generalization on the other side. Examples of generalized FGs created by this procedure are shown in the following section.
Organometallic structures were discarded and all molecules were standardized by removing counterions and neutralizing atomic charges. The most frequent FGs identified not counting aromatic heteroatoms are shown in Fig. The most common FG is amide present in Altogether our procedure identified FGs.
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To illustrate diversity of FGs a selection of some more exotic functionalities is shown in Fig. This shows that when analyzing functionalities in large chemical databases it is not sufficient to limit ourselves to a predefined list of patterns, but it is necessary to identify all FGs. Example of some exotic functional groups identified displayed as molecule cloud [ 15 ]. To validate this new approach a comparison with the current state-of-the-art program for identification of FGs—checkmol [ 6 ] was performed.
Checkmol analyses molecules and identifies FGs from a predefined set of functionalities.
Organic Functional Group Analysis: Theory and Development
The philosophy of checkmol is slightly different from that of our approach, checkmol defines FGs in a hierarchical manner so for comparison we used the most detailed substructure defined in checkmol. Comparison of the results, i. The results show very good agreement of the two methods. The differences are in most cases within tenth of percent. For the simple aromatic substituents checkmol identifies generally slightly less FGs than our approach for example arylchloride The largest differences between the 2 approaches may be observed for simple functionalities that are often part of the more complex FGs.
The most prominent example is alkene with checkmol result 8. The reason for this is the fact that the alkene is often part of relatively common more complex FGs for example acrylamide, acryloyl etc. Another such example is ketone 7. In summary, the agreement between the both approaches is very good. This shows that systems based on a well selected list of substructures as apparently checkmol is can provide useful information about the FG composition of general molecular datasets. The advantage of our algorithm of automatic identification of FGs is its ability to handle more complex FGs that are often present in specialized collections of molecules.
Examples identified by this simple analysis are activated alkenes that act as a Michael acceptors and are often used as covalent binders. Another advantage of the algorithmic approach over predefined set of substructures is more fine graining of the results like the detailed classification of ureas mentioned previously, that may be important for analyzing properties like solubility and the easy possibility to fine-tune the algorithm to fit the needs of a particular analysis for example library diversity or QSAR studies. The author is willing to provide help in any such endeavor.
The new method allows to analyze FGs in large chemical databases in a way that was not possible using previous approaches. The author wants to thank Dr. Richard Lewis for discussing the manuscript and for helpful comments. Peter Ertl www. I performed work on this manuscript as an employee of Novartis. No external funding was received.
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Published online Jun 7. Peter Ertl. Author information Article notes Copyright and License information Disclaimer. Peter Ertl, Email: moc. Corresponding author. Received Dec 20; Accepted May This article has been cited by other articles in PMC. Abstract Background The concept of functional groups forms a basis of organic chemistry, medicinal chemistry, toxicity assessment, spectroscopy and also chemical nomenclature. Results An algorithm to identify functional groups in a molecule based on iterative marching through its atoms is described.
Conclusions A new algorithm to identify all functional groups in organic molecules is presented. Graphical abstract.
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