Cornelis Altona

The relationship between proton-proton NMR coupling constants and substituent electronegativities—I : An empirical generalization of the karplus equation

A new coupling constant-torsion angle relation for the three-bond 1H-1H spin-spin coupling constant is formulated. The relation includes a correction for the electronegativity of substituents. The correction term is written as a function of the electronegativity, the H-C-C-H torsion angle, and the orientation of each substituent relative to the coupled protons. A dataset consisting of 315 experimental coupling constants was used to derive six empirical parameters by means of an iterative least-squares minimization procedure. The precision of the proposed equation, expressed as the root-mean-square deviation (0.48 Hz), is superior to any hitherto reported. It is shown that separate treatment of CH2CH2, CH2CH and CHCH fragments even improves this precision. An application in the field of monosubstituted cyclohexanes is given.

Conformation of non-aromatic ring Compounds—XXV: Geometry and conformation of ring D in some steroids from X-ray structure determinations☆

Abstract A quantitative description of (solid state) steroid ring D puckering and conformation in terms of maximum angle of torsion ϕ m and “phase angle” of pseudoration Δ has considerably improved the approach to the problem of describing flexible 5-membered rings. The maximal torsional parameter ϕ m of all steroid rings D is relatively constant (47°) although a slight tendency to increase with increasing phase angle is noted. The phase angles of 17-keto steroids are negative (= rotation toward C(14) envelope form), those of the otherwise substituted steroids are limited to a rather narrow range comprising about one quarter of the possible circuit. A C(13) envelope has not been found thus far. Some empirical rules that may serve as a basis for the discussion of ring D conformation can now be recognized. In first approximation the nature of the C(17) or C(16) β substituent (except keto) has no discernible influence. Extreme deformations of rings A, B and/or C do affect ring D. The effect of the angular methyl groups C(18) and C(19) cannot yet be assessed for lack of information on nor-steroids. X-ray studies on a diversity of well chosen compounds will be necessary to elucidate the role of each conformation-determining factor. Solution data (NMR, infrared, ORD, CD, and dipole moments), interpreted in accordance with the now established “conformation laws” of ring D, may be of considerable help in this respect.

Application of self-consistent-field ab initio calculations to organic molecules: II. Scale factor method for the calculation of vibrational frequencies from ab initio force constants: ethane, propane and cyclopropane

Self-consistent-field ab initio calculations of the equilibrium geometries, r calc e, and quadratic force constants for methane, ethane, propane, ethene, cyclopropane and cyclopropene have been carried out using an extended basis of contracted gaussian functions (4–31G). In the case of unstrained saturated molecules or parts of molecules a simple (anharmonicity) correction yields calculated structures for which the average deviation with ‘best’ experimental bond lengths and angles is 0·003 A and 0·4° respectively. Calculated carbon-carbon double bonds are typically too short by a constant amount (0·022 A). The average deviation of calculated and experimental bond angles about CH2 groups in three membered rings and those about sp2 hybridized carbons are 1·5° and 1·0° respectively. Quadratic force constants for symmetric stretchings are compared with force constants deduced from vibrational analysis. Trends and differences are discussed.The complete GVFF of ethane, propane and cyclopropane has been calculated from ab initio energies using an extended (4–31G) basis set. A scale factor method was developed to scale down the ab initio force constants in order to reproduce the experimental vibrational frequencies. The latter were taken from the literature. It was found that scale factors were transferable in the present series of molecules. A total of 180 vibrational frequencies of ethane, propane and cyclopropane and of a series of deuterated analogues were calculated using six scale factors. The average difference between the observed and the calculated frequencies amounted to 10·4 cm-1 or 0·74 per cent. A comparison was made with force constants obtained from minimal basis set (STO-3G) and INDO calculations.

Application of self-consistent-field ab initio calculations to organic molecules

Self-consistent-field ab initio calculations of the equilibrium geometries, r calc e, and quadratic force constants for methane, ethane, propane, ethene, cyclopropane and cyclopropene have been carried out using an extended basis of contracted gaussian functions (4–31G). In the case of unstrained saturated molecules or parts of molecules a simple (anharmonicity) correction yields calculated structures for which the average deviation with ‘best’ experimental bond lengths and angles is 0·003 A and 0·4° respectively. Calculated carbon-carbon double bonds are typically too short by a constant amount (0·022 A). The average deviation of calculated and experimental bond angles about CH2 groups in three membered rings and those about sp2 hybridized carbons are 1·5° and 1·0° respectively. Quadratic force constants for symmetric stretchings are compared with force constants deduced from vibrational analysis. Trends and differences are discussed.

Furanose sugar conformations in DNA from NMR coupling constants

Publisher Summary The flexible five-membered sugar ring plays a pivotal role in nucleic acid structure and dynamic behavior. Structural differences between A-, B-, and Z-type duplexes are intimately correlated with specific conformational ranges of individual (deoxy)-riboses. Moreover, within the B-DNA family at least, each sugar responds to its surroundings (e.g., the basestacking pattern) by an appropriate adaptation of its geometry. For this reason, it is highly desirable to obtain a maximum of detailed quantitative information on the “atomic” level for each individual sugar in a DNA chain with the aid of existing experimental techniques. The chapter provides information content embodied in sets of vicinal 1 H– 1 H nuclear magnetic resonance (NMR) coupling constants. The complete conformational analysis of a given interconverting furanose in the ideal case involves the determination of five independent parameters: P s , Ф s , P N , Ф N , and X s . This is done by the creation of a simultaneous and consistent fit of a set of experimental coupling constants for predicted values with the aid of a graphical method or a computer least squares fit.

Conformation of non-aromatic ring compounds—LII : NMR spectra and dipole moments of 2-alkoxytetrahydropyrans

Abstract The conformational equilibrium of six 2-alkoxytetrahydropyrans has been studied by means of vicinal coupling constants and dipole moments. The alkoxy group prefers the axial orientation to the extent of 0–1 kcal/mole, which is in agreement with earlier results. From the linear relationship between μ 2 and J it follows that out of the six possible conformers of the COCOC moiety, two (or three) predominate in the mixture, one axial and one (or two) equatorial forms. A comparison is made with the conformation of the anomeric alkoxy group with respect to the ring as found in pyranosides by X-ray analyses.Abstract The conformational equilibrium of six 2-alkoxytetrahydropyrans has been studied by means of vicinal coupling constants and dipole moments. The alkoxy group prefers the axial orientation to the extent of 0–1 kcal/mole, which is in agreement with earlier results. From the linear relationship between μ2 and J it follows that out of the six possible conformers of the COCOC moiety, two (or three) predominate in the mixture, one axial and one (or two) equatorial forms. A comparison is made with the conformation of the anomeric alkoxy group with respect to the ring as found in pyranosides by X-ray analyses.

Force field parameters for sulfates and sulfamates based on ab initio calculations: Extensions of AMBER and CHARMm fields

Ab initio self‐consistent field (SCF) Hartree‐Fock calculations of sulfates ROSO3(−1) (R = Me, Et, i‐Pr) and sulfamates RNHSO3(−1) (R = H, Me, Et, i‐Pr) were performed at the 4‐31G(*S*N) //3‐21G(*S*N) basis set levels, where asterisks indicate d functions on sulfur and nitrogen atoms. These standard levels were determined by comparing calculation results with several basis sets up to MP2/6‐31G*//6‐31G*. Several conformations per compound were studied to obtain molecular geometries, rotational barriers, and potential derived point charges. In methyl sulfate, the rotational barrier around the CO bond is 1.6 kcal/mol at the MP2 level and 1.4 kcal/mol at the standard level. Its ground state has one of three HCOS torsion angles trans and one of three COSO torsion angles trans. Rotation over 60° around the single OS bond in the sulfate group costs 2.5 kcal/mol at the MP2 and 2.1 kcal/mol at the standard level. For ethyl sulfate, the calculated rotational barrier in going from the ground state, which has its CCOS torsion angle trans, to the syn‐periplanar conformation (CCOS torsion angle cis) is 4.8 kcal/mol. However, a much lower barrier of 0.7 kcal/mol leads to a secondary gauchelike conformation about 0.4 kcal/mol above the ground state, with the CCOS torsion angle at 87.6°. Again, one of the COSO torsion angles is trans in the ground state, and the rotational barrier for a 60° rotation of the sulfate group amounts to 1.8 kcal/mol. For methyl sulfamate, the rotational barriers are 2.5 kcal/mol around the CN bond and 3.3 kcal/mol around the NS bond. This is noteworthy because sulfamate itself has a calculated rotational barrier around the NS bond of only 1.7 kcal/mol. These and other data were used to parameterize the well‐known empirical force fields AMBER and CHARMm. When the new fields were tested by means of vibrational frequency calculations at the 6‐31G*//6‐31G* level for methyl sulfate, sulfamate, and methyl sulfamate ground states, the frequencies compared favorably with the AMBER and CHARMm calculated frequencies. The transferability of the force parameters to β‐D‐glucose‐6‐sulfate and isopropyl sulfate appears to be better than to isopropyl sulfamate.

Application of self-consistent-field ab initio calculations to organic molecules: VI. Dimethylether: general valence force field scaled on experimental frequencies, infra-red and Raman intensities

The complete GVFF of dimethylether has been determined from ab initio (4–31 G) energies. The scale-factor method was applied to adjust seven scale factors on 85 experimental frequencies. The averag...

Conformational analysis of β-D-ribo-, β-D-deoxyribo-, β-D-arabino-, β-D-xylo-, and β-D-lyxo-nucleosides from proton–proton coupling constants

A new n.m.r. coupling constant torsion angle relation is utilized to explore the effect of exocyclic oxygen substituents at C-2′ and C-3′ on J1′2.′, J2′,3′, and J3′,4′ in the furanose ring of β-D-ribo-, β-D-arabino-, β-D-xylo-, and β-D-lyxonucleosides. The five vicinal couplings in β-D-deoxyribonucleosides are also investigated. Calculated coupling constants for the full pseudorotational itinerary at different values of the puckering amplitudes are given. It is shown that experimental coupling constants, taken from the literature, can be satisfactorily explained in all cases on the basis of a two-state (N/S)-model of the furanose pseudorotation. Good estimates of both N- and S- geometry and the conformational equilibrium constant in five-membered rings of ribose, deoxyribose, xylose, lyxose, and arabinose derivatives are given. The judicious use of geometrical information obtained by X-ray crystallographic studies appeared indispensable for this type of analysis.

Application of self-consistent-field ab initio calculations to organic molecules: V. Ethene: general valence force field scaled on harmonic and anharmonic data, infra-red and Raman intensities

The scale-factor method has been applied in order to derive the General Valence Force Field for ethene from ab initio (4–31 G) force constants. The use of five scale factors proved to be sufficient...