C. Benecke, R. Grund, A. Kerber, R. Laue, T. Wieland
Department of Mathematics, University of Bayreuth, D-95440 Bayreuth, Germany
The program system MOLGEN is a software tool for chemical education and research. It allows to generate and to visualize all the constitutional formulae (=connectivity isomers) corresponding to a given gross formula. In order to restrict the usually very big number of such isomers, the user can prescribe or forbid certain substructures and the class of the substance can be chosen. Moreover, MOLGEN also allows to compute all configurational isomers to a given structural isomer as well as their realizations in space.
A main topic at certain school classes, university lectures or seminars is the very large variety of hydrocarbon molecules such as the well known benzene. Therefore it is important to demonstrate to the students that there is not only the famous benzene ring that corresponds to the gross formula C6H6 but that there are many constitutions of that particular form. Few students probably know of the existence of 217 constitutional formulae, and they will be astonished to hear that about 50 of them have been observed in nature or laboratory up to now. It is quite clear that this fact and the particular example requires demonstration on the screen of a computer monitor.
MOLGEN provides a solution to that problem. It was awarded the German-Austrian University Software Prize 1993 as an excellent educational software in chemistry. Several schools, universities and chemistry companies in Germany use this program which is the result of a research project supported by the Deutsche Forschungsgemeinschaft for several years.
We will describe MOLGEN by presenting short examples taken from chemical education and research.
Consider, for example, benzene. The 217 constitutional formulae corresponding to its chemical formula C6H6 are obtained by MOLGEN within a fraction of a second.
After generation a visualization of the result is needed. In setting up the display a two-dimensional placement function is called for drawing the molecules. Having done this for the 217 isomers of benzene, you will see the well-known benzene ring showing up as number 214 (see Figure 1). The molecule no. 215 is benzvalene, which was in fact discovered just 25 years ago, while its existence had been postulated by E. Hückel already in 1937.
There are many cases, when we do not want to show or even to calculate all cases, but only the cases belonging to a given class of chemical substances. For example: The chemical formula for alkanoles is CnH2n+1OH, where the structural element OH, the hydroxyl group, is emphasized. In this particular case we want to compute or to see only such constitutional formulae that consist of n carbon atoms together with 2n+2 hydrogen atoms and a single oxygen atom which has to belong to a hydroxyl group. The interested user can easily enter the chemical formula C3H8O together with the substructure OH and check that there are in fact two connectivity isomers, whereas there are three of them if the existence of the hydroxyl group is not prescribed.
Next is a corresponding exercise taken from an A-level examination in chemistry at Bavarian high schools in 1992 which nicely allows to demonstrate the use of MOLGEN: In a first question the brutto formula for tartaric acid was derived as C4H6O6. The exercise continues:
1.2 During an acid-base titration it was discovered that 1 mol of tartaric acid is equivalent to 2 mol of sodium hydroxide. Derive all possible constitutional structures compatible with this result and the chemical formula derived in 1.1. ...
For the demonstration with MOLGEN the hint 1.2 should be interpreted as the existence of two substructures of the form COOH, which have to be prescribed. After entering all these together with the gross formula, MOLGEN produces 22 solutions. Their examination shows several of them containing substructures that are quite uncommon. For example, the solutions numbered 17 and 18 (among others) contain two bonded oxygens (peroxo groups).
If you want to abandon such cases, you may proceed as follows: Besides the two substructures COOH prescribe two hydroxyl groups OH in addition. Thus, after another run of the generator, only 4 constitutional formulae remain (all solutions containing two oxygen atoms between two carbon atoms were skipped). Two of these remaining 4 solutions show the hydroxyl groups attached to the same carbon atom, and so we may cancel them by an application of the Erlenmeyer Rule, which is still used in under-graduate chemistry. Finally we arrive at the two constitutional formulae suggested by the people who designed that exercise.
We recall that we started using MOLGEN from altogether 22 isomers, the final two solutions of the problem are the isomers numbered 1 and 4 (see Figure 2).
In practice, the chemist will see by inspection that several further restrictions must be imposed. Therefore the built-in graphical editor allows to isolate and to define substructures which are either prescribed or forbidden. Another run of the generator can respect these conditions, and so, in an interactive way, the total amount of isomers can be reduced to a significantly smaller set of candidates which must be examined.
MOLGEN allows to handle cases which were impossible before efficient generators became available. Here are a few remarks concerning applications in research:
If you enter, for example, the gross formula C12O2Cl4H4 together with the single substructure of the dioxin skeleton (substitutes removed), within a second you obtain from MOLGEN the 22 constitutional isomers of the dioxin that are shown in Figure 4.
Here is, finally, a complex problem from molecular structure elucidation in industry which we solved by using MOLGEN. The gross formula given was C22H25N3O3, and we were told that the molecule in question contains the following 6 non-overlapping substructures (macro atoms, in terms of MOLGEN) F1, ..., F6:
Using these substructures, the gross formula reduces to F1F2F3F4F5F6N2. MOLGEN obtains (after several steps which we won't describe in detail here) 2,337 constitutional formulae for that reduced gross formula, and after expansion it constructs 8,916 isomers. Now we used the following restrictions: no triple bond and ring sizes between 5 and 6. Only 201 candidates remained from which an expert easily obtained the correct solution:
MOLGEN runs under DOS, Windows, OS/2 and SUN Solaris. There exists a limited version for education and a full version for science and research. For more information contact the authors.
