Kinetics Study by Using NMR Spectroscopy

Kinetics Study by Using NMR Spectroscopy

Kinetics has been studies for long period of time. The knowledge of kinetics allows a better understanding of chemical reaction mechanism. For decades, spectroscopy is a typical way to investigate kinetics. In this review paper, a new powerful technique, NMR, will be discussed in terms of an efficient kinetics study tool.

Kinetics plays a very important role in understanding of reaction mechanism. The information from kinetics study can optimize the fundamental of the reaction, such as benefit drug design, drug metabolism, and other related industrial process. Various analytical techniques have been used for investigating kinetics data. Among these techniques, spectroscopy tools are particularly favorite method. For example, Ultraviolet spectroscopy is one of the wildly used techniques. The advantages of UV are short detecting time and convenience for liquid, solid and gas phase samples. UV spectra can give a lot of useful information such as maximal absorption wavelength, molar extinction coefficient and quantum yield. However, UV still has its own limitation. The spectrum of UV can only provide the absorption data, once the multi-peaks overlaid, the spectra can not separate them. Moreover, UV can not show the process of the reaction. For example, in a cis- to trans- reaction, UV spectrum is less powerful to indicate when does the cis- configuration transform into trans- or vise versa.

Recently, Nuclear Magnetic Resonance spectroscopy is introduced to investigating kinetics study, in order to overcome the limitation of UV. NMR is a rich information technique that it highly distinguishes from UV. NMR can not only provide the kinetics data in molecular level, but also structural information during the reaction. In this paper, several examples of kinetics study by different NMR methods will be discussed. The purpose is to illustrate that NMR is a powerful tool to investigate chemical reaction kinetics.

NMR of photochromic reaction
By definition, photochromic compounds are sort of chemical species that can convert to other species on irradiation. The original compounds and the compounds after converting have different absorption spectrum. Photochromic compounds are interested because of the variety of applications, such as ophthalmic glasses, optical filters and temporary or permanent memories.

In 2004, Delbaere et al., investigated the NMR spectroscopy to the mechanism understanding of photochromism. They presented the NMR studies of spirooxazines and benzo- and naphthopyrans. UV was applied to irradiate chemical species and the photoproducts were identified by 1D and 2D NMR. The thermal kinetics data was monitored by measuring the concentration of each species at certain time.
In their results, first of all, for the spirooxazines species, 1H NMR indicated the presence of two isomers. The Trans-Transoid-Cis (TTC) was highly
concentrated and the Cis-Transoid-Cis (CTC). These two isomers had identical resonances. Their kinetics values, including activation energy and thermal barrier were supported by other reported data. The magnitude was similarity which means the data from Delbaere et al., was valid. Delbaere et al., also reported this reaction appeared to be first order.
Secondly, Delbaere et al., studied the naphtha- and benzo- pyran family. The difficulty was those compounds were known as chromenes which made it uneasy to distinguish among all the photoproducts. Delbaere et al., used fluoro-substituted each compounds that were investigated in order to overcome this difficulty. This nucleus was used as an NMR molecular probe. The NMR experiment showed that all the photoproducts did not possess equivalent fluoro-phenyl groups. This resulted in four different isomers of photomerocyanines: TTC, CTC, CTT and TTT. The kinetics values were collected by regular time. This time dependent profile indicated the TTC and CTC were bi-exponential curves while CTT and TTT isomers seemed to remain stable during the experiment time.
In conclusion, Delbaere et al., mentioned that NMR was a promising tool for studying photochromic compounds. On one hand, the number and structural can be unambiguously determined. Moreover, NMR spectroscopy can improve the kinetics studies by directly monitoring of concentration of each species.

NMR of protein dynamic
Knowledge of protein dynamic can gives a deep understanding of protein function. Recently, NMR spectroscopy has became a significant technology in terms of structural biomolecular studies and protein dynamic. In particular, studies of the large protein with high molecular weight are now possible at a level of details. These details are previously reserved for much smaller systems.
In 2004, Kay reported a study of molecular dynamic over a wide time range by NMR spectroscopy. The goal of this study was to related function to dynamic of protein, including the kinetics and thermodynamics. Kay first mentioned that their group used 2H spin relaxation as a probe of picoseconds to nanoseconds dynamics in protein. Since this relaxation was dominated by well known quadrupolar interaction, study of dynamics was benefited by using deuteron. However, high resolution was needed for studying large numbers of sites at once. Then Kay pointed out a labeling strategy that the intensities of correlations in 1H-13C prepared uniformly 13C and fractionally deuterated proteins. Take methyl group as an example, the 13CH2D isotopomer was of interest and a magnetization transfer scheme, 1H13C2H(T)13C(t1)1H(t2), where T was the time during which 2H relaxation occurs and t1, t2 are acquisition time.