Experimental Data In Solution Research Articles

Reproducing the Solvatochromism of Merocyanines by PCM Calculations.

Polarizable continuum methods (PCM) have been widely employed for simulating solvent effects, in spite of the fact that they either ignore specific interactions in solution or only partially reproduce non-specific contributions. Examples of three solvatochromic dyes with a negative, a positive and a reverse behavior illustrate the achievements and shortcomings of PCM calculations and the causes for their variable success. Even when qualitatively mimicking non-specific solvent effects, departures of calculated values from experimental data may be significant (20-30%). In addition, they can utterly fail to reproduce an inverted behavior that is caused by significant specific contributions by the solvent. As shown through a theoretical model that rationalizes and predicts the solvatochromism of phenolate merocyanines based on DFT (Density Functional Theory) descriptors in the gas phase, PCM shortcomings are to be held responsible for its eventual failure to reproduce experimental data in solution.

Learning to evolve structural ensembles of unfolded and disordered proteins using experimental solution data.

The structural characterization of proteins with a disorder requires a computational approach backed by experiments to model their diverse and dynamic structural ensembles. The selection of conformational ensembles consistent with solution experiments of disordered proteins highly depends on the initial pool of conformers, with currently available tools limited by conformational sampling. We have developed a Generative Recurrent Neural Network (GRNN) that uses supervised learning to bias the probability distributions of torsions to take advantage of experimental data types such as nuclear magnetic resonance J-couplings, nuclear Overhauser effects, and paramagnetic resonance enhancements. We show that updating the generative model parameters according to the reward feedback on the basis of the agreement between experimental data and probabilistic selection of torsions from learned distributions provides an alternative to existing approaches that simply reweight conformers of a static structural pool for disordered proteins. Instead, the biased GRNN, DynamICE, learns to physically change the conformations of the underlying pool of the disordered protein to those that better agree with experiments.

A computational study of the effects of axial halogen substitutions of boron subphthalocyanines on their electronic spectra in solution and in the solid state.

Non-planar boron subphthalocyanine chloride is a talented photoelectric material and has been widely applied. In this paper, we have investigated the effects of axial halogen substitutions on electronic spectra of boron subphthalocyanines by combining DFT/TDDFT calculations and available experimental data in solution and in the solid state. We utilize long range separated density functional and polarizable continuum model to obtain the electronic structure and absorption spectra. The computed frontier molecular orbital energy matches well with experiment in dichloromethane and the simulated spectra correctly reproduce the trend of experiment in toluene. Furthermore, we model two configurations (convex-to-convex and concave-to-concave) of dimers of boron subphthalocyanines based on experimental structures in thin film: From F to Cl to Br substitution, the simulated wavelength of absorption peaks in the visible region slightly increases; in contrast, the absorption strength decreases. Moreover, our calculated results suggest that the convex-to-convex configurations of dimers may be the main contributors to the absorption spectra of X-BsubPC (X = F, Cl, Br) in thin film, though no experimental spectra of thin film of X-BsubPC (X = F, Br) yet. Finally, we find that CAM-B3LYP is able to reproduce the energy of frontier molecular orbitals quite well.

Co–C Bond Dissociation Energies in Cobalamin Derivatives and Dispersion Effects: Anomaly or Just Challenging?

Accurate Co-C bond dissociation energies (BDEs) of large cobalamin derivatives in the gas phase and solution are crucial for understanding bond activation mechanisms in various enzymatic reactions. However, they are challenging for both experiment and theory as indicated by an obvious discrepancy between experimental and theoretical gas phase data for adenosylcobinamide. State-of-the-art dispersion-corrected DFT and LPNO-CCSD calculations are conducted for the Co-C BDEs of some neutral and positively charged cobalamin derivatives with adenosyl and methyl ligands and compared with available experimental gas phase and solution data to resolve the controversy. Our results from various levels of electronic structure theory are fully consistent with chemical and physical reasoning. We show undoubtedly that the Co-C bonds in complexes with the bulky adenosyl ligand are indirectly enhanced by many ligand-host noncovalent interactions and that the overall BDE are larger than those with the small methyl ligand in the gas phase. The additional intramolecular dispersion and hydrogen-bond interactions are significantly but not fully quenched in aqueous solution. The theoretical results including standard continuum solvation and dispersion corrections to DFT are in full accordance with experimental solution data. This is in agreement with several successful joined experimental/theoretical studies in recent years employing similar quantum chemical methodology. We see therefore no empirical basis for questioning the reliability of current dispersion corrections like D3 or VV10 to standard density functional approximations neither for these compounds nor for organometallic chemistry in general.

Conformational preferences of furan- and thiophene-based arylamides: a combined computational and experimental study

We examine the conformational preferences of the furan- and thiophene-based arylamides, N-methylfuran-2-carboxamide (3) and N-methylthiophene-2-carboxamide (4), using a combination of computational methods and NMR experiments. The compound choice stems from their use as foldamer building blocks. We quantify the differences in the conformational rigidity of the two compounds, which governs corresponding foldamer conformations. Specifically, we demonstrate the effects of intramolecular hydrogen bonding (H-bonding), geometrical patterns and solvent polarity on arylamide conformations by comparing 3, 4 and previously studied ortho-methoxy N-methylbenzamide (1) and ortho-methylthio N-methylbenzamide (2). The study reveals that compound 3, despite its non-optimal S(5)-type H-bond geometry, retains a large portion of the H-bonded (eclipsed) conformation even in polar protic solvents. This behaviour is consistent with the quantum mechanical (QM) torsional energy profile. The percentages of H-bonded conformers that 3 retains are just slightly smaller than those of 1, which has a stronger S(6)-type H-bond. As for 2 and 4, the replacement of the O atom in 1 by an S atom in 2 results in a 70–90% loss of the H-bonded conformer in solution. However, the equivalent O to S replacement in 3 (leading to 4) causes only 15–30% loss of the eclipsed conformers in 4. Therefore, conformational preferences of 4 are very different from 2, in contrast to the similarity between 3 and 1. This study shows how the interplay of several forces modulates the conformational flexibility of arylamides. It also attests the strategy we are developing, which leads to accurate prediction of foldamer structure. The vital component of this strategy is the re-parameterization of critical force field parameters based on QM potential energy profiles, as well as validation of these parameters using experimental data in solution.

Advances in X-ray scattering: from solution SAXS to achievements with coherent beams

Small-angle X-ray scattering (SAXS) of macromolecular systems in solution has become an obvious complement to high resolution structural studies. Using SAXS, structural hypotheses can be directly tested against experimental data in solution. Conformational changes or complex formation can be monitored, and help understanding structure-function relationships. Additionally, the reliability of the data has been much strengthened by on-line purification approaches. Moreover, when coherent X-rays are used for sample illumination, SAXS patterns become speckled and can provide electron-density maps directly by computational phase-retrieval methods. Furthermore, X-ray free-electron laser with femtosecond pulse duration will enable us to take time-frozen images of biomolecules in solution free from radiation damage. In this paper, recent experimental and methodological advances in both classical and coherent SAXS are reviewed.

A DFT exploration of structural and electronic properties of a photoswitchable octapeptide cyclized with (4-aminomethyl)phenylazobenzoic acid

A systematic computational study is carried out on the intramolecular hydrogen bonding of cyclic azobenzene peptide containing photoswitch (4-aminomethyl)phenylazobenzoic acid (AMPB) and an octapeptide fragment, (Ala-Cys-Ala-Thr-Cys-Asp-Gly-Phe), at the B3LYP/6-31++G** level. Cis and trans AMPB impose different geometries to the octapeptide fragment so that the optimized structures show 5 and 6 different types of the inter- and intraresidue N H⋯O hydrogen bondings, respectively. Variations of chemical shielding isotropy, σ iso, of amide 1H, 15N, 17O, and 13C atoms as well as quadrupole coupling constant, C Q, and asymmetry parameter, η Q, of amide 14N, 2H, and 17O atoms are well correlated with the strength of the predicted N H⋯O hydrogen bondings. In spite of weaker hydrogen bonding on the nitrogen of Phe in the cis configuration compared to trans one, its σ iso and C Q parameters are unexpectedly lowered. Applying natural bonding orbital (NBO) analysis, this unexpected result is related to the occupation number of the lone pair of this nitrogen. The calculated chemical shifts of the residues which are supposed to be involved in intramolecular hydrogen bondings are close to the experimental data in solution. Applying conducting polarized continuum model (CPCM), to assess the solvent effect as a polarizable medium, does not greatly influence the 1H chemical shifts of these residues compared to those that do not contribute in the intramolecular hydrogen bodings. The results may confirm the existence of the theoretically predicted hydrogen bondings.

A reoptimized GROMOS force field for hexopyranose‐based carbohydrates accounting for the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers

This article presents a reoptimization of the GROMOS 53A6 force field for hexopyranose-based carbohydrates (nearly equivalent to 45A4 for pure carbohydrate systems) into a new version 56A(CARBO) (nearly equivalent to 53A6 for non-carbohydrate systems). This reoptimization was found necessary to repair a number of shortcomings of the 53A6 (45A4) parameter set and to extend the scope of the force field to properties that had not been included previously into the parameterization procedure. The new 56A(CARBO) force field is characterized by: (i) the formulation of systematic build-up rules for the automatic generation of force-field topologies over a large class of compounds including (but not restricted to) unfunctionalized polyhexopyranoses with arbritrary connectivities; (ii) the systematic use of enhanced sampling methods for inclusion of experimental thermodynamic data concerning slow or unphysical processes into the parameterization procedure; and (iii) an extensive validation against available experimental data in solution and, to a limited extent, theoretical (quantum-mechanical) data in the gas phase. At present, the 56A(CARBO) force field is restricted to compounds of the elements C, O, and H presenting single bonds only, no oxygen functions other than alcohol, ether, hemiacetal, or acetal, and no cyclic segments other than six-membered rings (separated by at least one intermediate atom). After calibration, this force field is shown to reproduce well the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers. As a result, the 56A(CARBO) force field should be suitable for: (i) the characterization of the dynamics of pyranose ring conformational transitions (in simulations on the microsecond timescale); (ii) the investigation of systems where alternative ring conformations become significantly populated; (iii) the investigation of anomerization or epimerization in terms of free-energy differences; and (iv) the design of simulation approaches accelerating the anomerization process along an unphysical pathway.

Absorption Spectrum of the Green Fluorescent Protein Chromophore: A Difficult Case for ab Initio Methods?

We perform a thorough comparative investigation of the excitation energies of the anionic and neutral forms of the green fluorescent protein (GFP) chromophore in the gas phase using a variety of first-principle theoretical approaches commonly used to access excited state properties of photoactive molecules. These include time-dependent density functional theory (TDDFT), complete-active-space second-order perturbation theory (CASPT2), equation-of-motion coupled cluster (EOM-CC), and quantum Monte Carlo (QMC) methods. We find that all approaches give roughly the same vertical excitation for the anionic form, while TDDFT predicts an excitation for the neutral chromophore significantly lower than the highly correlated methods. Our findings support the picture emerging from the extrapolation of the Kamlet-Taft fit of absorption experimental data in solution and indicate that the protein gives rise to a considerable bathochromic shift with respect to vacuum. These results also open some questions on the interpretation of photodestruction spectroscopy experiments in the gas phase as well as on the accuracy of previous theoretical calculations in the more complex protein environment.

Theoretical Study of the Reduction Mechanism of Sulfoxides by Thiols

Theoretical computations have been carried out to investigate the reaction mechanism of the sulfoxide reduction by thiols in solution. This reaction is a suitable model for enzymatic processes involving methionine sulfoxide reductases (Msrs). Recent investigations on the Msr mechanism have clearly shown that a sulfenic acid intermediate is formed on the catalytic cysteine of the active site concomitantly to the methionine product. In contrast, experimental studies for the reaction of a number of thiols and sulfoxides in solution did not observe sulfenic acid formation. Only, a disulfide was identified as the final product of the process. The present study has been carried out at the MP2/6-311+G(3d2f,2df,2p)//B3LYP/6-311G(d,p) level of theory. The solvent effect in DMSO has been incorporated using a discrete-continuum model. The calculations provide a basic mechanistic framework that allows discussion on the apparent discrepancy existing between experimental data in solution and in the enzymes. They show that, in the early steps of the process in solution, a sulfurane intermediate is formed the rate of which is limiting. Then, a proton transfer from a second thiol molecule to the sulfurane leads to the formation of either a sulfenic acid or a disulfide though the latter is much more stable than the former. If a sulfenic acid is formed in solution, it should react with a thiol molecule making its experimental detection difficult or even unfeasible.

Modeling ring puckering in strained systems: application to 3,6-anhydroglycosides

Different conformations of methyl 3,6-anhydroglycosides with the β- d- galacto, α- d- galacto, and β- d- gluco configurations were studied by molecular mechanics (using the program mm3) and by quantum mechanical (QM) methods at the HF/- and B3LYP/6-31+G** levels, with and without solvent emulation. Using molecular mechanics, the energies were plotted against the ϕ, θ puckering coordinates of Cremer and Pople. In such strained systems, only two extreme conformations of the six-membered ring are likely: 1 C 4 and B 1,4, or any one close to either of them. Results show the preponderance of a distorted chair conformation over that of the distorted boat, though the energy difference is lower and the distortions are larger for the compound with the β- d- galacto configuration. For derivatives of this compound, experimental data in solution indicate both chair and boat forms, depending on the compound and the solvent, whereas for the remaining compounds, experimental data always show the preponderance of the chair conformation. The more accurate DFT calculations lead to the lower energy differences, suggesting that HF and mm3 underestimate the stability of the boat-like conformations. Similar studies on model compounds depict the importance of the anomeric effect in the conformational preferences.

Understanding Sterol–Membrane Interactions Part I: Hartree–Fock versus DFT Calculations of 13C and 1H NMR Isotropic Chemical Shifts of Sterols in Solution and Analysis of Hydrogen‐Bonding Effects

1H and 13C NMR chemical shifts are exquisitely sensitive probes of the local environment of the corresponding nuclei. Ultimately, direct determination of the chemical shifts of sterols in their membrane environment has the potential to reveal their molecular interactions and dynamics, in particular concerning the hydrogen-bonding partners of their OH groups. However, this strategy requires an accurate and efficient means to quantify the influence of the various interactions on chemical shielding. Herein the validity of Hartree-Fock and DFT calculations of the 13C and 1H NMR chemical shifts of cholesterol and ergosterol are compared with one another and with experimental chemical shifts measured in solution at 500 MHz. A computational strategy (definition of basis set, simpler molecular models for the sterols themselves and their molecular complexes) is proposed and compared with experimental data in solution. It is shown in particular that the effects of hydrogen bonding with various functional groups (water as a hydrogen-bond donor and acceptor, acetone) on NMR chemical shifts in CDCl3 solution can be accurately reproduced with this computational approach.

Theoretical study of spiropyran–merocyanine thermal isomerization

Quantum mechanical computations at DFT level were carried out on the processes involved in the thermal reaction SP ⇆ ME, where SP is the nitro-substituted spirobenzopyran (1 ′,3 ′-dihydro-1 ′,3 ′,3 ′-trimethyl-6-nitro-spiro[2H-1-benzopyran-2,2 ′- [2H]indole]) in the closed form and ME is the corresponding open form. A detailed theoretical description of the overall reaction is reported along with the thermodynamic parameters for all intermediates and transition states. The obtained activation energy value is in agreement with the available experimental data in solution.

Basicity of lactones and cyclic ketones towards I2and ICl. An experimental and theoretical study

Intermolecular charge transfer (CT) spectra of several complexes between cyclic ketones and lactones and molecular iodine and iodine monochloride were studied in the UV-visible region. Equilibrium constant and free energy changes of the formed complexes were determined in solution. Ab initio calculations at HF/LANL2DZ* and MP2(full)/LANL2DZ* were carried out to establish the nature of the complexation site in the case of lactones, to determine the complex structures and to examine the ring size effect. Although range of the basicity towards I2 and ICl of compounds studied was small, it was found that cyclic ketones are more basic than lactones. This basicity difference decreases from small to large cycles and practically vanishes for six- and seven-membered rings. A comparative analysis between basicities of lactones and aliphatic esters towards I2 and ICl has also been carried out. Experimental data in solution were found to be linearly correlated with theoretical results in the gas phase. Proton affinities of cyclic ketones and aliphatic carbonyl compounds that do not present any secondary interaction with the Lewis acid correlate very well with their gas-phase basicity towards I2 and ICl.

Basicity of some carbonyl compounds towards iodine monochloride: experimental and theoretical study

Intermolecular charge-transfer (CT) complexes between a wide range of carbonyl compounds and iodine monochloride were spectroscopically studied in the UV–visible region. Equilibrium constants and Gibbs energy changes of 1:1 charge transfer complexes were determined in CCl4 solution. The ICl basicity scale in CCl4 of the set of carbonyl derivatives included in this study is well correlated with the I2 basicity scale in the same solvent. Ab initio calculations at HF/LANL2DZ* and MP2(full)/LANL2DZ* were carried out in order to clarify the structures of these CT complexes. Two different conformations, depending on the characteristics of the substituents, may be found. In one of them the ICl moiety lies in the plane of the carbonyl group, in the other the ICl subunit is perpendicular to the CO group. The perpendicular complexes are favored by bulky substituents for which the HOMO has a clear π-character. Both kinds of complexes can be spectroscopically distinguished since they present the CT absorption at different wavelengths. In both kinds of complexes the carbonyl–ICl interaction is essentially electrostatic. The substituent effects were analyzed through the use of the Taft–Topsom model. Experimental data in solution and theoretical estimates were found to follow a good linear relationship.

An Experimental and Theoretical Study on Some Thiocarbonyl−I2Molecular Complexes

Intermolecular charge-transfer (CT) spectra of several complexes between thiocarbonyl compounds and molecular iodine were studied in the UV−visible region. Equilibrium constants and Gibbs energy changes of 1:1 charge-transfer complexes were determined in solution. Two different kinds of complexes were detected, those which present the CT band in the 300 nm region and those which absorb around 350 nm. Ab initio calculations at HF/LANL2DZ* and MP2(full)/LANL2DZ*//LANL2DZ* were carried out to clarify their structure. Complexes with the CT band around 300 nm correspond to those where the molecule of iodine lies in the same plane of the CS group, while in those absorbing in the 350 nm region the I2 moiety is almost perpendicular to that plane. These perpendicular complexes are formed when the substituents around the thiocarbonyl group are voluminous, due to steric hindrance and to the different nature of the HOMO. In both kinds of complexes, the thiocarbonyl−iodine interaction is essentially electrostatic. The substituent effects were analyzed by Taft−Topsom's model. Experimental data in solution and theoretical estimates were found to follow a good linear relationship. The gas-phase basicity of the set of thiocarbonyl compounds investigated toward proton is linearly correlated with their basicity toward molecular iodine in solution. This finding strongly supports previous conclusions regarding the relationship between gas-phase and solution reactivity data.

NMR Shieldings in Benzoyl and 2-Hydroxybenzoyl Compounds. Experimental versus GIAO Calculated Data

GIAO-calculated NMR chemical shifts (1H, 13C, and 17O) as obtained at various computational levels are reported for the three parent compounds phenol, benzaldehyde, and salicylaldehyde, and for 13 different benzoyl and the 13 corresponding 2-hydroxybenzoyl compounds. The data are compared with experimental solution data, focusing on the agreement with spectral patterns and spectral trends. The influence of different optimized geometries (HF, MP2, B3LYP, BLYP), basis sets (6-31G(d,p) up to 6-311++G(2df,2dp)), and levels of theory (HF, B3LYP, BLYP) was investigated systematically by exhaustive calculations on the three parent compounds. With regard to the results obtained from this foregoing study, the GIAO calculations for the compounds of the two series were performed at two levels of theory, HF/6-311++G(d,p) and BLYP/6-311++G(d,p) for both the B3LYP/6-31G(d,p) and the HF/6-31G(d,p) optimized geometries. It turned out that, with the exception of the nuclei of the hydrogen-bonded OH groups, B3LYP and HF optimized geometries yield rather similar results. For aromatic carbons and protons, because of systematic shortcomings, the GIAO-HF calculations are distinctly worse than the GIAO-BLYP calculations. In the latter case, interchanges with respect to the experimental spectral patterns are obtained only in few instances and concern nuclei with rather small chemical shift differences (within 4 ppm for carbons, within 0.5 ppm for hydrogens). For the nuclei of the CO and O−H groups, the experimentally observed spectral trends are reproduced in similar quality at both the HF and the BLYP levels of theory.

Calculation of combinatory entropy in complex polymer solutions based on the Flory–Huggins theory

The combinatory entropy for two types of complex polymer solutions has been calculated based on the Flory–Huggins theory. The combinatory entropy for polymer solution with polymer chains consisting of two kind of parts, rod and flexible parts is given by: ΔS f–r /R= ΔS F–H /R+{1+β−(1−r −1)Φ 2} ln {1−Φ 2(1−r −1)/(β+1)}−(r −1+β)Φ 2 ln {1−(1−r −1)/(β+1)} where Δ S F–H/ R=− Φ 1 ln Φ 1−( Φ 2/ r) ln Φ 2 corresponds to the F–H theory, Φ i is the volume fraction of component ( i), r is the number of segment per polymer, β= a/ c where a is the number of segments in the flexible part and c is the number of segments in the rod part, m is the number of repeated units in a chain and the unit consists of a flexible part and a rod part and m( a+ c)= r−1. The combinatory entropy in the polymer solution where some solvent molecules interact with polymer segments strongly as `solvation' is given by: ΔS solv /R=−(1/r) ln Φ 2−{(1+ϵ) −1−Φ 2} ln {1−Φ 2(1+ϵ)} where ϵ is defined by ϵ= r s/ r and r s is the number of solvents solvated per polymer. Correlation between Δ S f–r in this work and those obtained by Guggenheim, Miller, Huggins and Kurata has been discussed and found that these are essentially the same. The partial molar entropy of solvent Δ S 1/ R in polymer solution calculated in this work agreed with those obtained based on the experimental data in solution of polyisobutylene in n-pentane where Δ S 1/ R is negative over low polymer concentration.

Conformational Studies of Chiral Vinylogous Sulfonamidopeptides

AbstractThe conformational preferences of chiral vinylogous aminosulfonic acids (vs‐amino acids) and of the corresponding oligomers (vs‐peptides) were investigated by a combination of X‐ray crystallography, variable‐temperature (VT) 1H NMR spectroscopy, FT‐IR spectroscopy, and NOE experiments. The major source of conformational freedom in the monomers is the rotation around the CC bond connecting the double bond with the allylic stereocenter (NC*CC). The allylic conformational preferences can be altered in the oligomers by the formation of secondary structures enforced by hydrogen bonding. Twelve‐membered‐ring hydrogen bonding is detected in the crystal structure of vs‐dipeptide 9, while fourteen‐membered‐ring hydrogen bonding is the most common folding pattern for the oligomers in chloroform solution. The experimental results are complemented by computer modeling: suitable force‐field (FF) parameters for the unsaturated sulfonamide group were developed from ab initio calculations. A Goodman–Still systematic pseudo‐Monte‐Carlo search was used for the conformational search. The conformers were minimized in chloroform with the GB/SA model. The calculations correctly predicted both the size of the hydrogen‐bonded ring and its relative importance, in agreement with the experimental data in solution.

The Perlin Effect: bond lengths, bond strengths, and the origins of stereoelectronic effects upon one-bond C–H coupling constants

The magnitude of a one-bond C–H coupling constant depends upon the chemical environment of the hydrogen atom and, especially, upon its stereochemical relationship to vicinal lone electron pairs. However, a lone electron pair is not essential for the observation of a stereoelectronic effect, since even cyclohexane exhibits different axial and equatorial C–H coupling constants. We propose the name "Perlin Effect" to describe such observations. An analysis of the extensive experimental data regarding the Perlin Effect reveals that, in cyclohexane and in six-membered rings having one or more heteroatoms of the first row attached to the carbon of interest, 1JC–H is always larger for an equatorial hydrogen than for an axial hydrogen. The magnitude of the Perlin Effect is reduced when the carbon carrying the hydrogen of interest is attached to first row and second row atoms or heteroatoms, and it reverses when the carbon atom carries two heteroatoms from below the first row.The existence of the Perlin Effect in nuclear magnetic resonance spectra is reminiscent of an infrared effect known as the Bohlmann bands, whose origin has previously been explained by quantitative perturbational molecular orbital (PMO) theory in terms of the effects of lone electron pairs upon the lengths and strengths and, therefore, the chemical reactivities of vicinal C—H bonds. Since the magnitude of a one-bond C–H coupling constant is expected to vary inversely with bond length, the origins of the Perlin Effect and of the Bohlmann bands would seem to be the same, i.e., the longer (weaker) C—H bond has the smaller one-bond coupling constant. This expectation has now been confirmed: for 25 molecules, representing a total of 35 different kinds of C—H bonds, the bond lengths, stretching force constants, and charge distributions have been determined from fully optimized 6-31G* molecular orbital calculations. In nine of ten cases for which experimental data exist for pairs of diastereomeric or diastereotopic hydrogens, the shorter C—H bond of the pair has the larger coupling constant; in the tenth case, the experimental difference is only 1–2 Hz. Moreover, a global analysis of the data in terms of the equation J = A + BqCqH + C/r, where J is an experimental coupling constant, q is a total atomic charge, and r is a C—H bond length, correlates 23 different types of C—H bonds linearly with a correlation coefficient of 0.915. The C parameter is the leading term of the correlation. Among the systems studied theoretically are eight molecules of the type CH3CHXY (Y = OH, SH; X = F, Cl, OH, SH), which are representative of systems containing both endocyclic and exocyclic first row and second row anomeric effects. The exocyclic effect is found to be very similar for first row and second row substituents, but the endocyclic effect is larger for the first row substituent. Both findings agree with experimental data in solution. Finally, quantitative PMO analysis has been employed to analyse the origins of the different C—H bond lengths in the various molecules of the study. Keywords: anomeric effect, PMO analysis, NMR, stereochemistry, molecular orbital calculations.