Rotamer population

This rotamer model for the fluorescence decay of an aromatic amino acid also predicts that the amplitudes of the kinetic components should correspond to the ground-state rotamer populations, provided that interconversion... 

W. R. Laws, J. B. A. Ross, H. R. Wyssbrod, J. M. Beechem, L. Brand, and J. C. Sutherland, Time-resolved fluorescence and H NMR studies of tyrosine and tyrosine analogues Correlation of NMR-determined rotamer populations and fluorescence kinetics, Biochemistry 25, 599-607 (1986). 

The functionalization of folded motifs is based on an understanding of secondary and tertiary structures (Fig. 2) and must take into account the relative positions of the residues, their rotamer populations and possible interactions with residues that do not form part of the site. For example, glutamic acid in position i has a strong propensity for salt-bridge formation, and thus reduced reactivity, if there is a Lys residue available i-4 in the sequence, but the probabihty is much less if the base is i-3 [60]. Fortunately, there is a wealth of structural information on the structural properties of the common amino acids from studies of natural proteins that provides considerable support for the design of new proteins. The naturally occurring amino acids have so far been used to construct reactive sites for catalysis [11-13], metal- and heme-binding sites [14,15,19,21,22] and for the site-selective functionalization of folded proteins [24,25]. 

Eliel et al. (72JA8587 76JA956) and Juaristi et al. (87JOC3806 90JOC33 92JA2157) studied the conformational behavior of 5-sulfur-substituted 1,3-dioxanes (see Table V) and discussed the results in terms of the rotamer population of the axial conformer in which steric, electrostatic, and stere-oelectronic effects are dominant. The sulfoxides place both the sulfinyl oxygen and the substituent outside the 1,3-dioxane ring in the sulfone, the position of the tBu substituent is similarly corroborated by an X-ray structure in the solid state. 

M. Kraszni, Z. Szakacs, and B. Noszal, Determination of rotamer populations and related parameters from NMR coupling constants A critical review, Anal. Bioanal. Chem., 378 (2004) 1449-1463. 

A number of studies on the fluorescence decay of tyrosine, tyrosine derivatives, and small tyrosyl peptides have been carried out. 36-38 Whereas the tyrosine zwitterion and tyrosine derivatives with an ionized a-carboxy group exhibited monoexponential fluorescence decay (x = 3.26-3.76 ns), double- or triple-exponential decay was observed in most other cases. As in the case of the tryptophan model compounds, the complex decay kinetics were again interpreted in terms of rotamer populations resulting from rotation around the C —Cp bond. There is evidence to indicate that the shorter fluorescence lifetimes may arise from rotamers in which the phenol ring is in close contact with a hydrated carbonyl group 36 37 and that a charge-transfer mechanism may be implicated in this quenching process. 39 ... 

An interesting example of the role of solvent in determining the conformation of the linear precursor and hence the relative stereochemistry in the product is provided by the thiamorpholine derivative (7) (90JHC1661). Deprotection of this by catalytic hydrogenolysis leads to cyclization yielding a mixture of (8) and (9). The product ratio depends on the solvent used for the hydrogenolysis. In methanol it is 35 54, whereas in dichloro-methane-acetic acid (20 1) the ratio is 56 9. Obviously the rotamer populations are influenced by the solvent chosen. 

It is known that the geometries of the reactants play an important role in the regio-and stereochemical outcome of radical reactions since they are commonly involved in early transition states. Previous attempts to affect rotamer populations during the reaction included, among others, control of temperature and addition of a Lewis acid. It was recently reported75 that organotin halides, common byproducts of radical reactions, act... 

The B3LYP/6-31+G(d,p) level of theory has been used to calculate the rotamer populations, the energy barriers, and the reaction path curvature for the SN2 identity... 

An intramolecular acyl radical cyclization of acyl selenide 1024 uses a (Z)-vinylogous sulfonate to control rotamer population, affording ry -2,6-disubstituted tetrahydropyran-4-one 1025, a key intermediate during synthesis of the tetrahydropyran unit of mucocin (Equation 399) <1997TL5249>. This methodology is also applicable to the synthesis of polycyclic ethers <1996JOC4880>. 

Based on all these considerations, we chose to develop a new type of chiral hydrazone, tailored for use in free radical addition reactions, which would incorporate Lewis acid activation [35-37] and restriction of rotamer populations as key design elements [1-7] (Fig. 2). 

Both effects 1 and 2 may be more or less obscured by the presence of heteroatoms on nitrogen or other polar groups which may also present solvent-dependent interactions. For instance when different rotamers are present, changing solvent may also affect the rotamer populations (or the equilibrium geometry of a single rotamer) and thus modify the inversion barrier. Such effects may occur, for instance, in hydroxylamine 86> and hydrazine 76> derivatives. 

The authors assume this reflects the rotamer population of the zwitterionic intermediate and that 51 arises by abstraction of an equatorial proton (Scheme 36). However, this would be more likely to occur via a twist conformation which could arise, at least in part, from equatorial attack on the enamine. Interestingly the tetrasubstituted enamine (51) crystallized from the reaction mixture and was shown on heating in benzene, without added acid catalyst, to revert to the same mixture of 51 and 52. This presumably reflects the greater carbon acidity of a methylene alpha to a sulphone group which can therefore catalyse the interconversion or cause reversion to enamine followed by re-alkylation100. 

Trifluoromethyl)phenylcopper was found to be an octamer by consideration of the kinetics of its decomposition, and by cryoscopy and vapor pressure osmometry in benzene solution 36). Its F NMR spectrum in ether at room temperature is a sharp singlet. Consequently, the suggested structure is a central copper cube with equivalent bridging benzotri-fluoride groups. The initial decomposition product, Cu8( n-CF3CgH4)e, is considered to be a Cu(0)—Cu(I) octanuclear cluster compound 36). For the octameric m-(trifluoromethyl)phenylcopper, the tetrameric ortho isomer, and pentafluorophenylcopper tetramer, the F NMR spectra were found to vary with temperature. The changes are not considered to involve important structural alterations, but only variations in solvent complexes and rotamer populations 32, 37). The spectra also... 

Table 4-7. Solvent dependence of the relative rotamer population (mole fraction of (30b)) and the standard molar Gibbs energy differences between rotamers of chloroacetaldehyde at 36 °C [87],...

Schnupf, U. Willett, J. L. Momany, F. DFTMD studies of glucose and epimers Anomeric ratios, rotamer populations, and hydration energies, Carbohydr. Res. 2010, 345, 503-511. 

The extensive pattern of dynamics that emerges from our simulations of TBP as an important contributor to complex formation is evident as well from the first structure of TBP obtained by NMR. The collection of 25 structures of a complex between TBP and an N-terminal domain of the largest TAFn in D.melanogaster, listed in Table 1 as ITBA, provides evidence for the dynamic properties of both TBP and the TAP fragment from the analysis of the different rotamers populated in the ensemble of structures. Such local variability in structure also obtains for the side chains at the recognition interface, lending further credibility to the results obtained in the molecular dynamics simulations described above. 

NMR spectroscopy to verify the conformation of I determined by H NMR. Those workers (21) reported that Jc4,m and Vc4,h6 equal 2.4 Hz, which would fix the conformation around the C5-C6 bond of I as shown in rotamer 9A. They also concluded that rotamer 7A was required to explain the observed coupling constants. Spoormaker and de Bie (30) suggested that no conformation was preferred around the C5-C6 bond, but instead that equal rotamer populations explained the observed data. 

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