Nuclear magnetic resonance case study

In a study being conducted at Case Western Reserve University under the direction of Dr. Lawrence Sayre, trifluoromethyl-substituted analogs of 2,5-hexanedione will be synthesized, compared with the parent compound in chemical model studies, and evaluated for neurotoxicity in rats. This is part of an effort to address how gamma-diketone-induced pyrrole formation at neurofilament-based lysine epsilon-amino groups leads to neurofilament accumulations. Nuclear magnetic resonance (NMR) studies will provide direct visualization of the nature of chemical modification. 

A careful nuclear magnetic resonance (NMR) study of the titration behavior of His-35 in Az-Ade by Canters and co-workers (Groeneveld et al, 1988) confirmed the prediction that His-35 would not titrate—or, at best, was found to have an unusually low pA (4.6). Interestingly, when His-35 is protonated there seems to be no effect on the copper center, unlike the case with Az-Pae. 

The hydroxides of berklium(III), Bk(OH)3, and califomium(III), Cf(OH)s, behave in a similar fashion [3]. In their crystalline forms, Am(OH)s and Cm(OH)3 are anhydrous (as are hydroxides of light rare-earth elements), and are hexagonal, C 6h P s/m space group, a = 6.420 and 6.391 A, c = 3.745 and 3.712 A, for Am and Cm compounds, respectively. Due to self-irradiation, the unit-cell parameters increase with time, as does the sample amorphization. In the case of " Cm(OH)3, the stmcture decomposes within 1 day, but the same process for " Am(OH)3 takes up to 4-6 months [4]. The Mossbauer spectrum of Am(OH)3 [5] is characterized by 5 = 4.6 cm/c (relative to Am02). The nuclear magnetic resonance (NMR) studies indicate that, among the TUE(III) hydroxides, the Am compound has the most covalent chemical bonds. The TUE(III) hydroxides are readily soluble in different mineral acids under these conditions, the solutions of hydrated An ions are produced. 

A-oxide (HATU), and l-(l-pyrrolidinyl-li7-l,2,3-triazolo[4,5-Z ]pyridin-l-ylmethylene)pyrrolidinium hexafluorophosphate A-oxide (29) (HAPyU) crystallize as aminium salts (guanidinium AT-oxides) [72,73]. Nuclear magnetic resonance (NMR) studies in the case of HAPyU showed that the same structure is found in solution [73]. TBTU (30) and TATU (31), the tetra-fluoroborate salts related to HBTU and HATU, have also been synthesized and incorporated in SPPS. The counterion (hexafluorophosphate or tetra-fluoroborate) does not appear to affect reactivity [74]. In addition, the tetra-fluoroborate derivatives are more soluble in DMF than their corresponding hexafluorophosphate salts. 

For instance, UV and nuclear magnetic resonance (NMR) studies of the reaction between A-methylacridinium ion and primary aromatic amines have revealed the formation of unstable N-adducts under kinetically controlled conditions (—50°C). Their formation is especially favored in case of anilines bearing in the /jara-position an electron-donating substituent R. At temperatures above 0°C, these N-adducts are gradually converted into thermodynamically more favored C-adducts. Also it has been shown that when no oxidant is added, the A-methylacridinium cation acts as oxidant of both N- and C-adducts, thus giving the corresponding products and 10-methyl-9,10-dihydroacridine (Scheme 36) [11, 136]. 

Chen, J., Dupradeau, R Y., Case, D. A., Turner, C. J., Stubbe, J. (2007). Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4 -oxidized abasic sites. Biochemistry, 46, 3096. 

Nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research has been used primarily in a classical, organic chemistry framework. Typical studies have included (1) the structure elucidation of compounds [1,2], (2) investigating chirality of drug substances [3,4], (3) the determination of cellular metabolism [5,6], and (4) protein studies [7-9], to name but a few. From the development perspective, NMR is traditionally used again for structure elucidation, but also for analytical applications [10]. In each case, solution-phase NMR has been utilized. It seems ironic that although —90% of the pharmaceutical products on the market exist in the solid form, solid state NMR is in its infancy as applied to pharmaceutical problem solving and methods development. 

A nucleus under study by nuclear magnetic resonance techniques is affected by other nuclei in the same molecule. This phenomenon is known as spin-spin coupling. The effect arises (in adjacent nuclei) from the two electrons joining the nuclei in a covalent bond. Suppose the energy of states in which the electrons in the bond have opposing spins is lower than the state in which the electron spins are parallel. Then the AE between the two states (in this case a negative number) is called the coupling constant, J, expressed in frequency units, Hz. Internuclear... 

Nuclear magnetic resonance (NMR) experiments are used to study the exchange kinetics of chemical systems in equilibrium.28,68,69 As is the case for fluorescence correlation spectroscopy no perturbation of the chemical system in equilibrium is required to obtain kinetic information from NMR experiments. However, NMR is not very sensitive to concentration changes. 

Nuclear magnetic resonance spectroscopy 10.6.3.2 Case study 2... 

---