Molecular dynamics and NMR

Grandi, T., Carrupt, P.A., Fruttero, R. and Testa, B. (2001) Molecular dynamics and NMR e5q)loration of ihe properly space of ihe zwitterionic antihistamine cetirizine. Helvetica Chimica Acta, 84, 360-374. 

Molecular dynamic and NMR studies have shown that only the extended conformation of CF3-acetyldocetaxel (i.e., in which the isoserine side chain is distant from the baccatine moiety) is independent of the hydrophilic or hydrophobic nature of the medium. In the other derivatives of Taxol, the globular conformation is largely favored by a protic medium. " Thus, it would be interesting to perform studies of complexes with tubuhnes in the solid phase to determine if the cytotoxic activity is connected with the conformation. 

Nordland, T. M., Andersson, S., Nilsson, L., Rigler, R., Grasland, A., and McLaughlin, L. W. (1989). Structure and dynamics of a fluorescent DNA oligomer containing the EcoRl recognition sequence Fluorescence, molecular dynamics, and NMR studies. Biochemistry 28, 9095-9103. 

A protocol combining molecular dynamics and NMR spectroscopy gave excellent agreement between calculated and experimental nuclear Overhauser effect (NOE) buildup curves of 2,5-oligo(2-thienyl)furans <2002PCA1277>. 

Case DA. Molecular dynamics and NMR spin relaxation in proteins. Acc. Chem. Res. 2002 35 325-331. 

A. Laaksonen and P. Stilbs, Molecular Dynamics and NMR Study of Methane-Water Systems, Mol. Phys., 74 (1991), 747. 

A. Laaksonen and H. Kovacs, Silvemitrate in Aqueous Solution and as Molten Salt A Molecular Dynamics and NMR Study, Can. J. Chem., 72(1994), 2278. 

N. Bouchemal-Chibani, I. Braccini, C. Derouet, C. Herve du Penhoat and V. Michon. Conformational Analysis of disaccharides using molecular dynamics and NMR methods. Int. J. Biol. Macromol. 17 (1995) 177. 

Nanosecond Molecular Dynamics and NMR Study of Conformational Transitions in the Sialyl-Lewis X Antigen. 

T. C. Beutler, T. Bremi, R. R. Ernst, and W. F. van Gunsteren, /. Phys. Chem., 100, 2637 (1996). Motion and Conformation of Side Chains in Peptides. A Comparison of 2D Umbrella-Sampling Molecular Dynamics and NMR Results. 

Fenchenko studied free induction decays and transverse relaxation in entangled polymer melts. He considered both the effects of the dipolar interactions between spins in different polymer chains and within an isolated segment along s single chain. Sebastiao and co-workers presented a unifying model for molecular dynamics and NMR relaxation for chiral and non-chiral nematic liquid crystals. The model included molecular rotations/ reorientations, translational self-diffusion as well as collective motions. For the chiral nematic phase, an additional relaxation mechanism was proposed, associated with rotations induced by translational diffusion along the helical axis. The model was applied to interpret experimental data, to which we return below. 

Angell and Burgess described the synthesis of j8-tum mimics by intramolecular copper(I)-catalyzed cycloaddition of dipeptide 72 in Scheme 10.22. However, they noted the prevalence to form dimeric cycloaddition products 74 instead of the desired macrocycle 73, and yields were low due to poor solubility of both products. Molecular dynamics and NMR were used to identify plausible type I and 11 jS-tum conformations for 73, however, the circular dichroism spectrum did not correspond to typical type 1 and 11 jS-tum structures and this discrepancy was not discussed further. Burke Jr. el al. reported the preparation... 

FIQ. 3 Diffusion coefficient of benzene molecules in benzene-polystyrene mixtures normalized by the diffusion coefficient of neat benzene molecular dynamics results, NMR measurements and prediction by the Mackie-Meares model [26]. 

The underlying physical principles of NMR have been established and are well understood.8 Applications of both solid- and solution-state NMR spectroscopy can be found in many different disciplines. It is routinely used in structural elucidation of organic and inorganic compounds, polymers, and biomolecules (e.g., proteins, nucleic acids, and carbohydrates). Additionally, NMR can be used to study molecular interactions (e.g., protein-protein and protein-ligand), molecular dynamics, and chemical reactions. It has also been used extensively in medical research and imaging (magnetic resonance imaging). 

Pursch, M., Vanderhart, D.L., Sander, L.C., Gu, X., Nguyen, T., and Wise, S.A., C30 self-assembled monolayers on sihca, titania and zirconia HPLC performance, atomic force microscopy and NMR studies of molecular dynamics and uniformity of coverage, J. Am. Chem. Soc., 6997, 2000. 

Schroder, L., Schmitz, C., and Bachert, P. (2004). Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized 1H NMR spectra. ]. Magn. Reson. 171, 213-224. 

Since NMR signal is sensitive to chemical environment, molecular dynamics, and position in space, obtained signal data contain mixture of these types of information. Separation of these types of information often requires detailed analysis using appropriate mathematical model. Improvement in methods and apparatus of NMR may allow us to use more precise mathematical models which are helpful for the separation. 

A conformational study of novel polyhydroxylated azepanes has been reported in which the 1H NMR spectroscopy and molecular modeling (molecular mechanics, molecular dynamics, and Monte Carlo methods) afforded insights into aspects of the conformational analysis <2004EJ04119>. 

NMR spectroscopy has also been used to study molecular dynamics and partial alignment of hydrogenated fullerenes in solution by relaxation measurements. 

Although the vast majority of H NMR studies on hydrogenated fullerenes have focused on structure determination, it can also be used to study molecular dynamics and partial alignment of the molecule in solution (see Section 9.7.1). 

The use of 19F NMR for a variable temperature (VT) NMR study of fluorinated taxoids is obviously advantageous over the use of H NMR because of the wide dispersion of the l9F chemical shifts that allows fast dynamic processes to be frozen out. Accordingly, F2-paclitaxel 65 and F-docetaxel 66 were selected as probes for the study of the solution structures and dynamic behavior of paclitaxel and docetaxel, respectively, in protic and aprotic solvent systems.77 The inactive 2, 10-diacetyldocetaxel (73) was also prepared to investigate the role of the 2 -hydroxyl moiety in the conformational dynamics.89 While molecular modeling and NMR analyses (at room temperature) of 73 indicate that there is no significant conformational changes as compared to paclitaxel, the 19F NMR VT study clearly indicates that this modification exerts marked effects on the dynamic behavior of the molecule.77... 

There is continuous progress in molecular dynamics and energy minimization. The main topics are force field improvement [26,53-56], incorporation of effective solvation term [57], b Initio modeling of small protein [49—5155.59], the incorporation of real data for x-ray refinement [60] and NMR structure determination [61], However, much work still has to be done to improve the force fields used for ensr"1 calculations before sn,r but trivial errors be detected... 

An important objective in materials science is the establishment of relationships between the microscopic structure or molecular dynamics and the resulting macroscopic properties. Once established, this knowledge then allows the design of improved materials. Thus, the availability of powerful analytical tools such as nuclear magnetic resonance (NMR) spectroscopy [1-6] is one of the key issues in polymer science. Its unique chemical selectivity and high flexibility allows one to study structure, chain conformation and molecular dynamics in much detail and depth. NMR in its different variants provides information from the molecular to the macroscopic length scale and on molecular motions from the 1 Hz to 1010 Hz. It can be applied to crystalline as well as to amorphous samples which is of particular importance for the study of polymers. Moreover, NMR can be conveniently applied to polymers since they contain predominantly nuclei that are NMR sensitive such as H and 13C. 

In addition to X-ray diffraction and NMR, which are direct techniques, methods based on the calculation of predicted three-dimensional structures of molecules in the range of 3 to 50 amino acids based on energy considerations are under rapid development. These approaches use what are commonly called molecular dynamics and energy minimization equations to specify the most probable conformation of polypeptides and small proteins. Often, when combined with information from other sources, such as X-ray crystallography or NMR studies, they have been demonstrated to be quite useful. However, when standing alone, their power and the accuracy of their predictive capability remains to be seen. 

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful analytical techniques in organic chemistry for elucidating the molecular structures of chemicals (1,2). Moreover, an NMR spectrum may be used like a fingerprint to identify a chemical by comparing it with its reference spectrum recorded from the authentic chemical under comparable conditions. The spectrum also reveals information on molecular conformation, isomerism, molecular dynamics, and diastereomers (3 6). 

Investigating molecular dynamics using NMR, in contrast to DS and LS, involves the application of several conceptually quite different techniques. For example, in spin-lattice relaxation studies one is concerned with familiar time correlation functions that are probed as spectral density point by point (Section II.D.2). In the case of line-shape analysis, usually a two-pulse echo sequence is applied, and the... 

The conformational analysis of oligothiophenes by use of a combined molecular dynamics (MD)/NMR spectroscopic protocol has been carried out. A series of MD simulations were performed for 2-(2-thienyl)-3-hexylthiophene 173, 2,5-bis(3 -hexyl-2 -thienyl)thiophene 176, and 2,5-bis(4 -hexyl-2 -thienyl)-thiophene 177, with a new MM2 torsional parameter set developed earlier for unsubstituted and methyl-substituted 2,2 -bithiophene. 

Although theoretically NMR can obtain both molecular dynamics and ordering, a close look at the literature shows that in membranes, NMR is used mostly for extracting order parameters. Much information on rotational mobility of membrane constituents is traditionally obtained using another magnetic resonance technique, ESR. ESR is extremely useful in the study of membrane fluidity, because of its unique time scale, which spans almost all motional range in membranes. 

Finally, NMR-derived distance information as well as information about dihedral angles (obtained from chemical shifts) is incorporated into structure calculations performed using molecular dynamics and simulated annealing programs such as CNS (48) and XPLOR-NIH (49) to calculate the protein stmcture. 

---