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.     

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.     

Use of 13C isotope shifts for assignment of deuterium labelling sites in 1,3-diphenylpropan-1-one

¹³C NMR spectroscopy was used for the unequivocal analysis of the mixture of products of RuCl₂[P(C₆H₅)₃]₃-catalysed transfer deuteriation of benzylideneacetophenone by (a) DCOONa/H₂O, (b) HCOONa/D₂O and (c) DCOONa/D₂O. Signal assignments in the ¹³C spectra were obtained mainly from the deuterium-induced ¹³C isotope shifts. The geminal ¹³C? ²H shift of the β-carbon of deuteriated 1,3-diphenylpropan-1-one is almost twice that for the α-carbon.     

Factor analysis of deuterium isotope effects on 13C NMR chemical shifts in Schiff bases

We have analyzed deuterium isotope effects on (13)C chemical shifts in a series of o-hydroxy Schiff bases by applying factor analysis. Two orthogonal factors were obtained that explain about 80 and 10 % of the variance of the data. The numerical values of these factors can be related to 1H NMR chemical shifts of the proton involved in the intramolecular bonds delta(XH) (X = O or N). Such a relation allows one to identify clusters of compounds with different tautomeric forms of hydrogen bonding. Application of a similar approach to solution 13C NMR chemical shifts produces three important factors, which have a different structure to factors describing isotope effects. This illustrates well the different nature of chemical shifts and isotope effects. The three factors explain about 54, 15, and 13 % of variance. They can be rationalized and are strongly related to the electronic properties and location of substituents.     

Simple synthesis of deuterium and 13C labeled trifluoromethyl phenyldiazirine derivatives as stable isotope tags for mass spectrometry

The synthesis of trifluoromethyl diazirine with a stable isotope tag is reported. We found that both Friedel-Crafts acylation and reduction of aryl carbonyl to methylene, using commercially available stable-isotope reagents, were utilized for the synthesis of diazirinyl fatty acid derivatives. The stable isotope labeled diazirine may be valuable for identifying binding sites by mass spectrometry.     

Unusually large deuterium isotope effects on one-bond 13C, 1H coupling constants in trans-stilbene challenged

The reported apparent large decrease in ¹J(C-α, H-α) by 1.75±0.20 Hz on replacement of one of the olefinic protons by deuterium in trans-stilbene is due to improper first-order analysis of the ¹H-coupled ¹³C spectrum of the parent compound. Consequently, the implied conformational difference between trans-stilbene and α-deuterio-trans-stilbene, which was used to explain the result, is not substantiated.     

Use of13C chemical shift/charge density linear relationship for ranking chemical structures

A novel approach to molecular structure elucidation based on ranking chemical structures in agreement with the¹³C NMR chemical shift/charge density linear relationship is suggested. The structure having the lowest standard approximation error (SAE) is considered to be the correct one. Each ranked structure is additionally tested for the¹³C chemical shift equivalence corresponding to its constitutional symmetry (in terms of the charge densities).This paper is Part VI of the series Automatic assignment of¹³C NMR signals. For Part V see ref. [1].     

A new secalonic acid. Linkage between tetrahydroxanthone units determined from deuterium isotope 13C chemical shifts

The previously unknown secalonic acid G has been isolated from Pyrenochaeta terrestris, and its structure determined by circular dichroism and ¹³C nmr techniques including deuterium isotope ¹³C chemical shift measurements to identify the linkage between the tetrahydroxanthone units.     

Impact of the deuterium isotope effect on the accuracy of 13C NMR measurements of site-specific isotope ratios at natural abundance in glucose

The application of isotope ratio methods in authenticity and traceability relies on the accuracy and robustness of the methodology employed. An unexpected source of error has now been identified, which can introduce major and variable inaccuracies into the determination of site-specific isotope ratio measurement by quantitative ¹³C NMR spectrometry if not correctly controlled. This is the isotope chemical shift effect, which comes into play when hydrogen atoms in the target molecule enter into exchange with deuterated water present at trace levels in the deuterated solvent used as the frequency lock. Even at a level of contamination as low as 0.02%, an error of 5‰ can be introduced, fivefold the required accuracy of 1‰. How to avoid this source of error is discussed.     

Intramolecular hydrogen bonding of novel o-hydroxythioacetophenones and related compounds evaluated by deuterium isotope effects on 13C chemical shifts

A new class of compounds, the 2-hydroxythioacetophenones, and related compounds have recently been synthesized. The hydrogen-bond system has been characterized by NMR chemical shifts and deuterium isotope effects on these as well as by DFT calculations. Use of solid-state (13)C NMR has enabled measurements of the intrinsic deuterium isotope effects of the most abundant tautomer of beta-thioxoketones. The compounds show very interesting long-range deuterium isotope effects on the thiocarbonyl carbon. The intramolecular hydrogen bonds of o-hydroxythioacetophenones are found to be slightly stronger than those of the corresponding acetophenones. The reactivity and stability of the compounds can be related to hydrogen bonding and to the presence of electron donating substituents.     

Computation of deuterium isotope perturbation of 13C NMR chemical shifts of alkanes: a local mode zero-point level approach

Replacement of H by D perturbs the (13)C NMR chemical shifts of an alkane molecule. This effect is largest for the carbon to which the D is attached, diminishing rapidly with intervening bonds. The effect is sensitive to stereochemistry and is large enough to be measured reliably. A simple model based on the ground (zero point) vibrational level and treating only the C-H(D) degrees of freedom (local mode approach) is presented. The change in CH bond length with H/D substitution as well as the reduction in the range of the zero-point level probability distribution for the stretch and both bend degrees of freedom are computed. The (13)C NMR chemical shifts are computed with variation in these three degrees of freedom, and the results are averaged with respect to the H and D distribution functions. The resulting differences in the zero-point averaged chemical shifts are compared with experimental values of the H/D shifts for a series of cycloalkanes, norbornane, adamantane, and protoadamantane. Agreement is generally very good. The remaining differences are discussed. The proton spectrum of cyclohexane- is revisited and updated with improved agreement with experiment.     

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 chemical shift subsitituent parameters for alkyllithium compounds in hydrocarbon solvents

¹³C chemical shift substituent parameters are presented for carbons α, β, γ, and δ to the lithium atom based on the chemical shifts of 14 ⁶Li-enriched alkyllithium compounds. The chemical shift of the carbon α to lithium depends on the branching of alkyl group at the α-carbon and on the aggregation state of the alkyllithium compound. Increased branching results in increased upfield shifts. This is interpreted in terms of the varying electronic nature of the alkyllithium compounds. The chemical shift of the carbon β to lithium substitution is shifted downfield approximately 5 ppm from the corresponding carbon in the parent hydrocarbon, irregardless of the alkyl group or the aggregation state of the alkyllithium compound. The chemical shift of the γ-carbon depends on the steric requirements of the alkyl group. Carbons four or more bonds from lithium have the same chemical shift as those of the parent hydrocarbon. The derived chemical shift parameters are used to assign the α-carbons of two alkyllithium compounds formed from the reaction of t-butyllithium and trimethylvinylsilane.     

Modified MINDO/3 13C chemical shift calculations for simple hydrocarbons

Calculations of ¹³C chemical shifts in some simple hydrocarbons have been carried out using the GIAO approach in the MINDO/3 semiempirical formalism. In order to achieve reasonable agreement with experiment it is necessary to modify (increase) the vacant orbital energies in the MINDO/3 calculation in order to reduce the magnitude of the paramagnetic contribution, and to also modify this dominant term by generally reducing it as a function of the number of hydrogen and carbon atoms bonded to the resonant nucleus in question. For a set of 34 resonant nuclei of the simpler hydrocarbons, agreement with experiment of the order of 7.8 ppm is attained; however, pathological cases such as cyclopropane and some simple allenes continue to cause problems, increasing the standard deviation of the full set to 12.5 ppm. Our results indicate that the MINDO/3 approach is as viable for ¹³C chemical shift calculations as other semiempirical approaches, all of which seem currently to be limited to a standard deviation of the order of 10 ppm.     

A steric deuterium isotope effect in 1,1,3,3-tetramethylcyclohexane

The equilibrium isotope effect (EIE) for the interconversion of the two chair isotopomers of 1-trideutero-1,3,3-trimethylcyclohexane was predicted using geometry and vibrational force constants derived from electronic structure theory at HF, B3LYP, and MP2 levels as input for the program THERMISTP. Agreement between theory and previously reported NMR results is very good (experimental K(eq) = 1.042 +/- 0.001 vs K(eq) = 1.0409 at MP2/6-311G* level, K(eq) = 1.0503 at HF/6-311G*, and K(eq) = 1.0417 at B3LYP/6-311G* level, all at 17 degrees C). In order to investigate the origin of this isotope effect, the calculated EIEs for the monodeuterated isotopomers were analyzed. It has been shown that the hydrogen atom on an axial methyl group which is unusually close to its counterpart on the other axial methyl is responsible for the large (steric) isotope effect in the compound studied.     

Use of an internal reference in 13C chemical shift measurements

The use of the nominal value of the chemical shift of the solvent to calibrate the spectrometer in ¹³C NMR spectroscopy was found to introduce errors due to the effect which the solute has on the solvent. In addition, hexamethyldisiloxane (HM) is proposed as an internal standard; owing to its high boiling point it is easier to manipulate than tetramethylsilane (TMS) and it is therefore possible to prepare solutions of known concentrations. In order to convert the data obtained with this standard to the TMS scale, the chemical shift of HM was determined in 16 solvents using cyclohexane as external standard in a spherical cell (5% w/w concentration of HM) as a function of the solvent factor g². Comparing these results with a similar plot obtained previously for TMS by other workers, it is possible to convert one type of data to the other by a simple linear expression.     

Counterintuitive deshielding on the 13C NMR chemical shift for the trifluoromethyl anion

The trifluoromethyl anion (CF₃⁻) displays ¹³C NMR chemical shift (175.0 ppm) surprisingly larger than neutral (CHF₃, 122.2 ppm) and cation (CF₃⁺, 150.7 ppm) compounds. This unexpected deshielding effect for a carbanion is investigated by density functional theory calculations and decomposition analyses of the ¹³C shielding tensor into localized molecular orbital contributions. The present work determines the shielding mechanisms involved in the observed behaviour of the fluorinated anion species, shedding light on the experimental NMR data and demystify the classical correlation between electron density and NMR chemical shift. The presence of fluorine atoms induces the carbon lone pair to create a paramagnetic shielding on the carbon nucleus.