Structures of Conjugated Heterocycles

The parent heterocycles— pyridine, pyrrole, furan, and thiophene— proved to be straightforward to deal with, following the scheme outlined above. Many other molecules of increasing complexity, contaiiung two or three heteroatoms, and up to the size of porphin, were treated. These molecules were found to be unexceptional as far as molecular mechanics is concerned, and calculations on them pretty much yielded the expected results. However, when the nucleic acid bases were examined, unexpected difficulties arose. 

From a biological point of view, there are a few relatively simple nitrogen heterocycles that occur in DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), and 

We wished, of course, to be sure that we could calculate structures such as these adequately with molecular mechanics. 

At this point (early 1980s) it became clear that we really needed to divide the treatment of aromatic heterocycles into two different, general cases. The first case is ordinary heterocyclic molecules. For those, the calculations are carried out as previously described. The second case would be when we wished to carry out a calculation on a macromolecule such as DNA, which has a great many molecules of nucleic acid bases present, and we do not want to do a quantum mechanical calculation on each of them one by one. We wished to carry out the quantum mechanical calculation for a given base once, and then develop a force field that will reproduce the structure of each of these bases adequately. These molecular force fields are then stored in a library. For future calculations involving those molecules then, one obtains from the library the appropriate force field for each of those molecules as needed, and they are then used in the ordinary molecular mechanical manner. 

We had earlier done this for the particular case of a benzene ring, which can be treated by the general method most of the time, but when it occurs multiple times in a macromolecule (or other large system), there is a general force field for the benzene ring that can be transferred into the calculation, which avoids having to carry out the quantum mechanical part of the calculation on each individual benzene. By this 

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