Chemspider (who has been doing some useful things recently with making data available and on which I shall comment separately) criticizes our work on NMR prediction by GIAO methods, and says he doesn’t “get it”. So I will continue to try to explain.
A Publication Comparing NMR Prediction Approaches
Those of you frequenting this blog might have read my highly opinionated views of what was originally entitled “Open Notebook Science NMR” (1,2). My views around that work were very strong…in fact I didn’t really “get it”. I didn’t get why GIAO approaches for NMR prediction (with all of the stated limitations) would be done to prove that you could validate NMR assignments by comparing predictions with assignments made experimentally . It’s known that NMR prediction can validate structures – it’s done on a daily basis in commercial software tools. I was involved in building tools like that for over a decade so what was to prove?
PMR: This is a scientific experiement to see if Quantum mechanical methods can predict NMR shifts. The emphasis is on Quantum Mechanics. Does Quantum Mechanics agree with experimental data? At heart it’s as simple as that. Many results of quantum mechanics are not observable – the wavefunction for example. A few things are observable. The geometry. Aspects of the energy. And the interaction of the wavefunction with the nucleus.
The original GIAO method had deviations from experimental. Were these deviations due to experiment or problems with theory. Henry Rzepa thought the methodology needed improvement. So he created new basis sets. He also calibrated the effect due to spin-orbit coupling. Our research has confirmed that the spin orbit coupling effect exists and is of a reproducible magnitude. That wasn’t clear before.
As we continue to get better data we may or may not discover new effects. If so they may be discoveries in physics – who knows?
Physical science works in large maprt by comparing theories with experiment. This is the basis of PhysML about which I may write later. The Open NMR experiment is about comparing theory and experiment. It is NOT about predicting as many structures as rapdily as possible by empirical means. It is about the fundamental ability to predict the properties of matter through quantum mechanics.
We have done exactly the same for molecular geometry. It could be argued that rather than calculating the geometry of a crystal we should simply make it and measure it. We have, for example, showed that many current QM programs are not capable of calculating crystal structures well. That’s a deficiency of the theories and the programs. By highlighting the differences we help to develop better methodology in fundamental theory. That is an unarguable approach in science.
From the practical point of view there are huge numbers of molecules than cannot be well predicted by the empirical NN or HOSE methods. Transition metal compounds. Anything that cannot be represented by a connection table (no-one has responded to my request as to how NN or HOSE would calculate molecules such as Li4Me4). The view of chemistry seen through connection tables is necessarily limited. The view through QM is not.
There are also many chemical effects that can be investigated through QM. It is possible that there are clear and systematic effects due to solvation (e.g. on C=O groups). QM may be able to model these atomistically (i.e. with explicit solvent). NN cannot do this. And there are many more aspects of chemistry where NMR shifts gives us a window on reality through QM calculations.
But first we have to get some believable Open Data to work with. Then we shall start to create new science.