Conformational equilibrium in 8-methyl-cis-2-thiahydrindane and 8-methyl-cis-2-oxahydrindane by 13C NMR spectroscopy

The preferred conformation of 8-methyl-cis-thiahydrindane has been both estimated by ¹³C NMR chemical shifts and determined by low temperature ¹³C NMR spectroscopy to be the conformer with the methyl group equatorial with respect to the cyclohexane ring. This result is in disagreement with the interpretation of the temperature dependence of the CD spectra of (+) and (?) 8-methyl-cis-2-thiahydrindane, whereby the conformation with the methyl group axial with respect to the cyclohexane ring was claimed to be the preferred conformation. The preferred conformation of the related oxygen heterocycle, 8-methyl-cis-2-oxahydrindane, has been estimated by ¹³C NMR chemical shifts to be the conformer with the methyl group axial with respect to the cyclohexane ring. Possible reasons for these observations are discussed.     

Conformational equilibria in isomeric methylcyclohexanols studied by 13C NMR spectroscopy

The conformational equilibrium constants for isomeric methylcyclohexanols (cis- and trans-1,2-, 1,3- and 1,4-methylcyclohexanols) have been determined from peak area measurements in the completely proton decoupled low temperature ¹³C NMR spectra of the individual conformers. The ¹³C chemical shifts are discussed in terms of the additive model.     

On the models for deuterium long-range isotope effects in13C NMR spectroscopy

The long-range deuterium isotope effects on¹³C nuclear shielding are physically not yet completely understood. Two existing models for explaining these effects, vibrational and substituent, are compared here. The vibrational model is based on the Born-Oppenheimer approximation, but it can explain only one-bond deuterium effects. To the contrary, the substituent model may explain many long-range isotope effects, but it is controversial due to the assumption of some distinct electronic properties of isotopes. We explain how long-range deuterium isotope effects may be rationalized by the subtle electronic changes induced by isotope substitution, which does not violate the Born-Oppenheimer approximation.     

Deuterium isotope effects in 13C NMR spectroscopy: Stereochemical assignment of monodeuteriated allylic alcohols.

Vicinal deuterium isotope effects on 13C NMR chemical shifts, ³ΔC (Φ) are given for ten monodeuteriated allylic alcohols. The relationship found for nine of them: 3ΔC(0°) ≅ 5/3 x ³ΔC(180°) allows the stereochemical assignement of their deuterium labeling. This assignment is in agreement with that from the Karplus-type relationship of vicinal coupling constants, ³J_C-D(Φ).     

Comparative conformational studies of cyclic derivatives by 13C NMR spectroscopy

The ¹³C chemical shift of the substituted or functionalized carbon of various medium and large rings is plotted against ring size (6–15 carbons). The curves thus obtained allow a conformational analysis of the corresponding derivatives.     

Conformational analysis of ochratoxin a by NMR spectroscopy and computational molecular modeling

Two-dimensional NMR spectroscopy has been used for a complete assignment of the proton and carbon-13 spectra of the metabolite from Aspergillus ochraceus, ochratoxin A. In addition, phase-sensitive nuclear Overhauser effect spectrometry experiments and computational molecular modeling (MM2 and MMFF force field programs) have been employed to examine the conformational properties of ochratoxin A in chloroform solutions. Particular attention has been given to intramolecular hydrogen-bonding formation involving the phenolic group on dihydroisocoumarin, which may be responsible for the toxic mechanism of ochratoxin A.     

Conformational study of 1,2-cycloundecadiene by dynamic NMR spectroscopy and computational methods

Solutions of 1,2-cycloundecadiene in propane were studied by low-temperature (13)C NMR spectroscopy. A total of 17 peaks were observed at -166.7 degrees C, corresponding to two conformations of similar populations, one of C(1) symmetry (11 peaks) and the other of C(2) symmetry. The line shapes show that the predominant pathway for exchange of the topomers (C(1) and C(1)') of the C(1) conformation does not include the C(2) conformation. From the (13)C spectra, free-energy barriers of 8.38 +/- 0.15, 9.45 +/- 0.15, and 9.35 +/- 0.15 kcal/mol were determined for the C(1) to C(1)', (C(1) + C(1)') to C(2), and C(2) to (C(1) + C(1)') conversions, respectively, at -72.2 degrees C. The NMR results for this compound are discussed in terms of the conformations predicted by molecular mechanics calculations obtained with Allinger's MM3 program. Ab initio calculations of free energies are also reported at the HF/ 6-311G level for 25 conformations.     

Conformational studies of novel estrogen receptor ligands by 1D and 2D NMR spectroscopy and computational methods

The solution conformations of the novel estrogen receptor ligands (17α,20E)‐(p‐trifluoromethylphenyl)vinylestradiol ( 1 ) and (17α,20E)‐(o‐trifluoromethylphenyl)vinylestradiol ( 2 ) were investigated in 2D and 1D NOESY studies and by comparison of ¹³C NMR chemical shifts with theoretical shieldings. The ¹H and ¹³C assignments of 1 and 2 were determined by DEPT, COSY and HMQC experiments. The conformations of the 17α‐phenylvinyl substituents of 1 and 2 are of interest because of their differing receptor binding affinities and effects in in vivo uterotrophic growth assays. A statistical method of evaluating contributing conformers of 1 and 2 from predicted ¹³C shifts of possible structures correlated fairly well with conformational conclusions derived from the NOE data. The 17α substituents of 1 and 2 apparently exist in similar conformational equilibria, suggesting that while 1 and 2 would occupy a similar receptor volume, interactions with the protein may shift the equilibrium and thereby influence the expression of the ligand. Copyright © 2003 John Wiley & Sons, Ltd.     

13C and 15N NMR study of acyclic vicinal diastereoisomers. Conformational effects

Conformations of aliphatic diastereoisomers with vicinal asymmetric centers (2,3-disubstituted butanes and 5,6-disubstituted n-decanes) are discussed in terms of their ¹³C and, in some cases, ¹⁵N chemical shifts and spin-lattice relaxation times. Solvent and protonation effects are explained by conformational changes in the isomers.     

Structural and kinetic studies on uranyl(V) carbonate complex using 13C NMR spectroscopy

We have measured 13C NMR spectra of uranyl(V) carbonate complex in D2O solution containing 1.003 M Na2(13)CO3 at various temperatures. Two singlet signals corresponding to free and coordinated CO3(2-) were observed at 169.13 and 106.70 ppm, respectively. From the peak area ratio, the structure of the uranyl(V) carbonate complex was determined as [U(V)O2(CO3)3]5-. Furthermore, kinetic analyses of the exchange reaction of free and coordinated CO3(2-) in [U(V)O2(CO3)3]5- were carried out using 13C NMR line-broadening. As a result, the first-order rate constant at 298 K and the activation parameters for CO3(2-) exchange reaction in [U(V)O2(CO3)3]5- were evaluated as 1.13 x 10(3) s(-1) and deltaH(double dagger) = 62.0 +/- 0.7 kJ x mol(-1), deltaS(double dagger) = 22 +/- 3 J x mol(-1) x K(-1), respectively. We suggest that the exchange follows a dissociative mechanism as in the corresponding [U(VI)O2(CO3)3]4- complex.     

Unusual deuterium isotope effects in 13C NMR spectra of trans-stilbene

A detailed analysis of the ¹³C NMR spectra of trans-stilbene and ten deuteriated trans-stilbenes has been undertaken. Some unusual deuterium isotope effects on carbon–hydrogen spin–spin coupling constants could not be explained by the ordinary primary and secondary isotope effects. The positive and negative changes of ⁿJ(CH) were interpreted in terms of a steric effect, the vibrational influence of the C? D bond and the para-effect induced by deuterium. In this respect, deuterium behaves as a real substituent with electronic properties different from those of hydrogen. The deuterium isotope effects on ¹³C NMR chemical shifts and carbon–deuterium coupling constants have also been determined.     

Conformational study of anticholinesterase carbamates in the furylbenzene series by 1H and 13C NMR spectroscopy

The structural analysis of carbamates derived from 2-(α-furyl)benzaldoximes and 2-(α-furyl)benzyl alcohols was carried out by ¹H and ¹³C NMR spectroscopy. The conjugative and steric effects of alkyl substituents introduced on the benzene rings were found to modify the relative orientation of the aromatic and furan rings. The existence of a close relationship between the stereochemistry of the studied compounds and their anticholinesterase activity has been proposed.     

Conformational studies by dynamic NMR. 91. Conformational stereodynamics of tetraethylmethane and analogous C(CH2X)4 compounds

Variable-temperature NMR studies of tetraethylmethane (1a), tetrapropylmethane (1b), tetrachloromethylmethane (1c), tetrabromomethylmethane (1d), tetracyclopropylmethylmethane (1e), and tetrabenzylmethane (1f) show a range of dynamic behavior. Separate signals for two types of conformation are observed for 1a, 1c, and 1d at low temperatures, with more than 95% of the molecules in a time-averaged D2d conformation, and the S4 conformation as the minor populated alternative. Compound 1e populates only S4-type conformations but equilibrates slowly between degenerate versions of these at low temperatures. Compounds 1b and 1f show a temperature-dependent spectrum but the low-temperature limit spectrum could not be observed. Ab initio calculations agree well with experiment on the conformational equilibria and suggest in particular that compounds 1b and 1f behave similarly to compounds 1a and 1e, respectively. A crystal structure of compound 1f is reported.     

Conformational analysis by HRMAS NMR spectroscopy of resin-bound homo-peptides from C(alpha)-methyl-leucine

A series of [L-(alphaMe)Leu]n (n = 1-5) homo-peptides have been covalently linked to Tentagel and POEPOP resins and submitted to a conformational study using HRMAS NMR spectroscopy. Whereas the mono- and dipeptide are mainly fully-extended, stable 3(10)-helical structures are formed beginning from the trimer.     

Investigations by (13)C NMR spectroscopy of ethene-initiated catalytic CO hydrogenation

13C NMR spectroscopy shows that the n-alkene and n-alkane products from the catalytic hydrogenation of CO in the presence of (13)C(2)H(4) probes over Ru/150 degrees C, Co/180 degrees C, Fe/220 degrees C, or Rh/190 degrees C (1 atm, CO:H(2) 1:1, "mild conditions") contain terminal (13)CH(3)(13)CH(2)- units. This is consistent with their formation by a regiospecific polymerization of C(1) species derived from CO and initiated by (13)C(2)H(4). Although the activities toward individual products differed somewhat, similar distributions and similar product labeling patterns were obtained over all the four catalysts. 1-Butene and the higher 1-n-alkenes from all the catalysts were largely (13)CH(3)(13)CH(2)(CH(2))(n)()CH=CH(2) (n = 0-3), propene formed over Ru or Co was (13)CH(3)(13)CH=CH(2), while both (13)CH(3)(13)CH=CH(2) and (13)CH(2)=(13)CHCH(3) were formed over Fe or Rh. Comparison of the conclusions from these probe experiments with those from isotope transient experiments by other workers indicates that the ethene initiator does not significantly modify the course of the CO hydrogenation. The reaction products are largely kinetically determined, and the primary products are mainly linear 1-n-alkenes, while the n-alkanes and 2-n-alkenes largely arise via secondary processes. Since the distribution of products and the labeling in them is so similar, it is concluded that one basic primary mechanism applies over all the four metals. Several different reaction paths involving a polymerization of surface methylene, [CH(2(ad))], have been proposed. Although the predictions based on several of these mechanisms agree with many of the results, the alkenyl + [CH(2(ad))] mechanism, initiated by a surface vinyl [CH(2)=CH((ad))], most easily accommodates the experimental evidence. An alternative path involving sequential addition of surface methylidyne and hydride either to a growing alkylidene chain (alkylidene + [CH(ad) + H(ad)]) or to an alkyl chain (alkyl + [CH((ad)) + H(ad)]) has recently been proposed by van Santen and Ciobica. The [CH(2(ad))] mechanism offers an easier explanation for the formation of the various alkenes, the distribution of products, and of the initiation, while the [CH(ad) + H(ad)] mechanism can explain any n-alkanes formed as primary products and not derived from alkenes. At higher reaction temperatures over Ru and Co, considerable (13)C(1) incorporation (from natural abundance in the CO and from cleavage of the (13)C(2)H(4) probe) was found in all the hydrocarbons. Thus, at higher temperatures (13)C(1(ad)) in addition to (13)C(2(ad)) species participate in both chain growth and initiation. In summary, adsorbed CO is transformed very easily into surface C(1(ad)), probably [CH(2(ad))] in equilibrium with [CH((ad))+H(ad)], which act as the propagating species.     

Acyclic forms of [1-(13)C]aldohexoses in aqueous solution: quantitation by (13)C NMR and deuterium isotope effects on tautomeric equilibria

High-resolution (13)C NMR spectra (150 MHz) have been obtained on the complete series of D-aldohexoses (D-allose 1, D-altrose 2, D-galactose 3, D-glucose 4, D-gulose 5, D-idose 6, D-mannose 7, D-talose 8) selectively labeled with (13)C at C1 in order to detect and quantify the percentages of acyclic forms, and to measure and/or confirm percentages of furanoses and pyranoses, in aqueous solution. Aldehyde and hydrate signals were detected for all aldohexoses, and percentages of these forms at 30 degrees C ranged from 0.006 to 0.7% (hydrate) and 0.0032 to 0.09% (aldehyde). Aldehyde percentages are largest for the altro, ido, and talo configurations, ranging from 0.01 to 0.09%; the ido configuration yielded the most hydrate (0.74%). Hydrate/aldehyde ratios vary with aldohexose configuration, ranging from 1.5 to 13, with gluco exhibiting the smallest ratio and gulo the largest. (2)H Equilibrium isotope effects (EIEs) on aldohexose anomerization were measured in D-galactose 3 and D-talose 8 selectively (13)C- and (2)H-labeled at C1 and H1. The (2)H isotope effect on (13)C chemical shift, and broadband (1)H- and (2)H-decoupling, were exploited to permit simultaneous observation and quantitation of the protonated and deuterated molecules in NMR samples containing equimolar mixtures of D-[1-(13)C]aldose and D-[1-(13)C; 1-(2)H]aldose. Small (2)H EIEs were observed for 8, but were undetectable for 3. These results suggest that configuration at C2 influences the magnitude of the (2)H isotope effect at H1 and/or that the observed effect cannot be reliably interpreted due to complications arising from the involvement of acyclic aldehyde forms as intermediates in the interconversion of cyclic forms. The observed (2)H isotope effects on aldohexose tautomeric equilibria provide new insights into the important question of whether (2)H substitutions can alter aldofuranose ring conformation, and lead to the identification of an optimal (2)H- and (13)C-substituted 2-deoxyribofuranose isotopomer on which to investigate this potential effect.     

13C NMR studies on radical anions. Special solvent effects

The determination of radical ions is crucial in mechanistic studies of reactions in which single electron transfer is suspected. A ¹³C NMR method based on the interaction of radical anions with tetrahydrofuran (THF) molecules is presented; measurements of the broadening of the THF α-carbon signal allow determination of the substrate concentration in the range 0.2–1.2 M . The spectacular effect observed on addition of small amounts of benzene greatly improved the method. In addition, studies of the spin-lattice, T₁, and of the transverse nuclear, T₂, relaxation times and of the effects of added co-solvents allow the proposal of the bonding situation and of the degree of coordination in the radical anion-cation-THF molecules' complex.     

Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 13C nuclear magnetic resonance

The 13C-NMR spectrum (Fig. 2,1) of cyclooctapeptide cyclo(L-phe-L-Pro-Gly-L-Pro)2 (A) in CDC13 suggested that its conformation involved the coexistence of two kinds of C2-symmetric conformation with trans-trans-trans-trans and cis-trans-trans-trans forms. Adding 0.5 equivalent of CsSCN or one equivalent of DL-Phe-OMe.HCl to the solution of cyclopeptide (A) in CDC13 yielded 13C-NMR spectra (Fig. 2,2 and Table I) which suggested a single C2-symmetric conformation with trans-trans-trans-trans form, resulting from the formation of complexes with CsSCN or DL-Phe-OMe.HCl. The 13C-NMR spectrum of complexes of A with DL-Phe-OMe.HCl displayed separate resonances for C(gamma), C(o), C(m), C(alpha), and C(beta) of D-Phe-OMe.HCl and L-Phe-OMe.HCl (Table I).