Tuesday, 22 January 2008

Mspin and Diasterotopic 1H NMR Assignment using 3J and RDCs

Scalar coupling constants, in particular vicinal (3J) couplings, are widely used in NMR for the determination of relative stereochemistry and preferred conformation of molecules. A number of different empiric equations to correlate the dihedral angle with the 3J values have been proposed, the Karplus equation being the most famous. The NOE (nuclear Overhauser effect) experiment is also extensively used, primarily, to define the stereochemistry within a molecule. Unlike scalar couplings, its mode of operation relies on the direct, through-space interaction between nuclei, and is independent of the presence of through-bond couplings.
However, both NOE and scalar coupling have limitations for measuring the structure information between atoms which are far apart. In addition, there are cases in which the 3J or NOE values of different stereoisomeric compounds are very similar so unambiguous assignment is not possible.
On the other hand, residual dipolar coupling (RDC) is able to provide global orientations between remote internuclear vectors, and thus gives a potential solution to these limitations. RDC’s have been widely used for the analysis of proteins and nucleic acids, but to a lesser extent in the small molecules area. Roberto Gil et al. have just published an article in which they propose the use of PMMA as a novel alignment media and discuss in a very nice way the unambiguous stereochemistry and assignment determination of the diastereotopic protons of Ludartin.

Stretched Poly(methyl methacrylate) Gel Aligns Small Organic Molecules in Chloroform. Stereochemical Analysis and Diastereotopic Proton NMR Assignment in Ludartin Using Residual Dipolar Couplings and 3J Coupling Constant Analysis
Gil, R. R.; Gayathri, C.; Tsarevsky, N. V.; Matyjaszewski, K.
J. Org. Chem.; (Article); 2008; ASAP Article; DOI: 10.1021/jo701871g

Roberto Gil and collaborators have used Mspin to calculate RDCs and 3J coupling constants for Ludartin. Below is an excerpt from the original article:

[...] The Mspin package includes modules for the calculations of 3J coupling constants, RDCs, and NOEs from 3D structures. Its usage is straightforward, and it can run on multiple platforms. For non-NMR experts, solving the structure using RDCs would be no longer a difficult task

Should you be involved in NMR structure elucidation, I believe you will find Mspin a very valuable tool, and we would very much appreciate your feedback on this application, which is currently in alpha version. It is available for download from here.

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