[Messi]

Hi guys,

I have a philosophy about organic chemistry and I was wondering what you guys think about it. I always thought that to truly understand organic chemistry at a very high level, one also needs to have a a great understanding of physical chemistry.  Sure, it is great that in organic chemistry you can know all your name reactions and a bunch of reaction mechanisms, but to truly understand what is going on at the microscopic level you must understand physical chemistry.

I believe that understanding what is happening at the microscopic level (molecular orbitals, energy levels) will allow you to to understand what is going on at the macroscopic level which is usually what we see in organic chemistry (ie: creating macromolecules). Sometimes when creating these macromolecules we run into problems with something "simple" not working and we don't understand why.

By tying in physical chemistry with organic chemistry one truly understands what is happening in the reactions an organic chemist is doing. I know Roald Hoffman made of computers/physical chemistry to solve long time organic chemistry problems.

I was wondering if anyone shared my thoughts or if anyone has ever written about this matter before?

[fledarmus]

This has been a frequent topic of discussion and research since the field of physical chemistry has existed. You would be able to get so much more accurate a picture of the entire reactive process if you could just calculate everything out from first principles. These are called ab initio calculations, and they have indeed proven extremely helpful in understanding a great number of reactive processes.

The issue with organic chemistry and even more with bioorganic chemistry is that the universe is just so big. Calculations that are trivial for 2 atoms sharing one electron, more difficult for two atoms sharing two electrons, and geometrically more complex as you add more atoms and more electrons are mind-bogglingly complicated by the time you get to useful organic molecules, and proteins are beyond the pale.

So the use of physical chemistry in organic chemistry has been a study in how much of the microscopic level can you simply ignore. Rather than trying to calculate every single orbital in every single fragment, orbitals are calculated where they are expected to be useful, and parameters are established to generally describe the parts of the molecule that are not calculated. With varying degrees of success, of course.

It's almost like trying to convince artists that they should mix their colors by measuring the absorbance of their pigments at various wavelengths, then calculating the mixture of pigments that would give them the spectrum of absorbance that they want for their color mixture. Sure, they could do it that way, but the point of the art is to get the color on paper, and the fastest way to do that is still to have an experienced artist mix the colors on the palette, adding pigments until they reach the desired color. A few weeks of calculation may tell you exactly what will happen in a reaction, but in many cases it is faster to get the answers you need just by mixing the compounds in the lab.

There are, of course, places where this is not true, and that is where physical chemistry has contributed greatly to the understanding of organic and bioorganic systems. In particular, the amino acids have been parameterized to the point where computer models of protein folding have contributed greatly to the understanding of enzyme systems and the effect of mutations on tertiary structure, resulting in leaps forward in computer-aided drug design.