Structure by NMR

AMU Bonvm, R Boelens, R Kaptem. Determination of biomolecular structures by NMR Use of relaxation matrix calculations. In WF van Gunsteren, PK Weiner, AI Wilkinson, eds. Computer Simulation of Biomolecular Systems Theoretical and Experimental Applications, Vol 2. Leiden ESCOM, 1993, pp 407-440. 

The first step in determination of a structure by NMR spectroscopy involves assignment of individual proton resonances. Development of high-field spectrometers and the use of a second dimension (2D-NMR) along with isotopic substitution (11) and sophisticated pulse sequences (12) make it possible to almost completely assign the proton spectrum of proteins of about 15 kD molecular weight (13—17). Some 2D-pulse sequences commonly used in the study of macromolecules are shown in Figure 1. 

The generation of carbocations in strongly acidic media, and the characterization of their structure by NMR in the 1950s was a breathtaking accomplishment that led to the award of the Nobel Prize in Chemistry to George Olah. Over the past 50 years NMR spectroscopy has evolved as the most important experimental method for the direct study of structure and dynamics of carbocations in solution and in the solid state. Hans-Ullrich Siehl provides an excellent review of computational studies to model experimental NMR spectra for carbocations. This chapter provides an example of how the fruitful interplay between theory and experiment has led to a better understanding of an important class of reactive intermediates. 

In the isoelectronic series (butadiene)M( j8 — CgHg) (M = Ti, Zr, Hf), the Hf complex exhibits an NMR spectrum at > 30 °C consistent with an envelope flip (AG = 17.6 kcalmol-1). The same process can be detected for the Zr complex at > 40 °C only via magnetization transfer experiments (AG > 20 kcalmol-1). The Ti complex exhibits a static structure by NMR spectroscopy16. 

Traditionally, the structural characterization of designed proteins is carried out by CD spectroscopy, which unfortunately provides only limited structural information at the atomic level. As the understanding of protein design develops more proteins appear that have well-defined structures and the determination of their solution structures by NMR spectroscopy is clearly the main tool for elucidating structure-function relationships. Key information is obtained simply from the ID spectrum (Fig. 7). 

Reynolds FR, Enriquez RG, Choosing the best pulse sequences, acquisition parameters, postacquisition processing strategies, probes for natural product structure by NMR spectroscopy, JNat Prod 65 221—244, 2002. 

Consequently, it is not surprising that the rate ratio for solvolysis of 99 100 was found to be greater than 2.5 x 106 and that at 150°C 100 did not solvolyze at all.395 This evidence is kinetic. Unlike the cases of the cyclobutene—1,3-diene and cyclohexadiene—1,3,5-triene interconversions, the direct product here is a cation, which is not stable but reacts with a nucleophile and loses some of its steric integrity in the process, so that much of the evidence has been of the kinetic type rather than from studies of product stereochemistry. However, it has been shown by investigations in super acids, where it is possible to keep the cations intact and to study their structures by nmr, that in all cases studied the cation that is predicted by these rules is in fact formed.396... 

Structures determined by spectroscopic means are generally underdetermined in that the number of variables is similar to or greater than the number of observations. In such cases, the energy-minimized structures can be used to aid in the refinement of the structure or as a check on the geometry[51]. Applications of molecular mechanics modeling to the determination of solution structures is described in detail in Chapters 6, 7, and 9. Such approaches are fundamental to the determination of macromolecu-lar structures by NMR spectroscopy. 

Broadhurst CL, Schmidt WF, Reeves JB, et al. 1997. Characterization and structure by NMR and FTIR spectroscopy, and molecular modeling of chromium(IH) picolinate and nicotinate complexes utilized for nutritional supplementation. J Inorg Biochem 66 119-130. 

The nmr spectrum of compound 72 shows steric hindrance due to the phenyl group. The spectrum shows therefore six signals of identical intensity for the three me2Si groups. Identification of meSi groups and BrCH2Si groups is easily achieved, but formation of derivatives is necessary in order to determine the total structure by nmr-spectroscopy. 

Boekelheide and his collaborators sought to distinguish between these possible structures by NMR-spectroscopy (92). The olefinic region... 

Similar difficulties occur in attempts to study solution structures by NMR spectrometry. Here ligand exchange is the problem. A further difficulty in H NMR spectrometry is the multiple splitting of the hydride resonance by both 103Rh and 3IP nuclei in the molecule. The ultimate example is found in [RhH(PF3)4] where every nucleus in the molecule has a non-integral spin. It has been calculated that the hydrido resonance should be split into 130 peaks 192... 

The 1-methylcyclobutyl cation 8, which can also be considered as equilibrating 1-methylcyclopropylcarbinyl cations, was shown to have a nonclassical structure by NMR spectroscopic studies in conjunction with Saunders isotopic perturbation of equilibria techniques. 

Determining structure by mass spectrometry Determining structure by NMR spectroscopy Determining structure by infrared spectroscopically chl5... 

This is one question that X-ray answers better than any other method what shape does a molecule have Another important problem it can solve is the structure of a new imknown compound. There are bacteria in oil wells, for example, that use methane as an energy source. It is amazing that bacteria manage to convert methane into anything useful, and, of course, chemists really wanted to know how they did it. Then in 1979 it was found that the bacteria use a coenzyme, given the trivial name methoxatin , to oxidize methane to methanol. Methoxatin was a new compoimd with an unknown structure and could be obtained in only very small amounts. It proved exceptionally difficult to solve the structure by NMR but eventually methoxatin was found by X-ray crystallography to be a polycyclic tricarboxylic acid. This is a more complex molecule than hexanedioic acid but X-ray crystallographers routinely solve much more complex structures than this. 

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