Showing papers on "Conformational isomerism published in 1989"

An internal-coordinate Monte Carlo method for searching conformational space

Abstract: An internal coordinate, random-search method for finding the low-energy conformations of organic molecules is described. The search is biased toward the low-energy regions of conformational space by choosing starting geometries for each step in the conformational search from among previously stored low-energy conformers. Tendencies of the search method to concentrate in certain regions of conformational space at the expense of others are reduced by uniform usage of stored structures as starting geometries and by using varying numbers or torsional rotations in each step. Tests of the procedure's ability to find all low-energy conformations of several acrylic, medium- and large-ring molecules are described. Direct comparisons of the method with Cartesian coordinate random methods and systematic internal coordinate grid searches are carried out with symmetrical and unsymmetrical molecules. The method makes it possible to carry out global conformational searches on symmetrical and unsymmetrical molecules having up to a dozen variable torsion angles.

Quantitative determination of conformational disorder in the acyl chains of phospholipid bilayers by infrared spectroscopy.

Abstract: A method is proposed and demonstrated for the direct determination of conformational disorder (trans-gauche isomerization) as a function of acyl-chain position in phospholipid bilayer membranes. Three specifically deuterated derivatives of dipalmitoylphosphatidylcholine (DPPC), namely 4,4,4',4'-d4-DPPC (4-d4-DPPC), 6,6,6',6'-d4-DPPC (6-d4-DPPC), and 10,10,10',10'-d4-DPPC (10-d4-DPPC), have been synthesized. The CD2 rocking modes in the Fourier transform infrared (FT-IR) spectrum have been monitored as a function of temperature for each derivative. A method originally applied by Snyder and Poore [(1973) Macromolecules 6, 708-715] as a specific probe of hydrocarbon chain conformation in alkanes has been used to analyze the data. The rocking modes appear at 622 cm-1 for a CD2 segment surrounded by a trans C-C-C skeleton and between 645 and 655 cm-1 for segments surrounded by particular gauche conformers. The integrated band intensities of these modes have been used to monitor trans-gauche isomerization in the acyl chains at particular depths in the bilayer. At 48 degrees C, above the gel-liquid-crystal phase transition, the percentage of gauche rotamers present is 20.7 +/- 4.2, 32.3 +/- 2.3, and 19.7 +/- 0.8 for 4-d4-DPPC, 6-d4-DPPC, and 10-d4-DPPC, respectively. The gel phase of the latter two molecules is highly ordered. In contrast, a substantial population of gauche rotamers was observed for the 4-d4-DPPC. The conformational analysis yields a range of 3.6-4.2 gauche rotamers/acyl chain of DPPC above the phase transition. This range is in excellent accord with the dilatometric data of Nagle and Wilkinson [(1978) Biophys. J. 23, 159-175]. The significant advantages of the FT-IR approach are discussed.

Rotational barriers: 4. Dimethoxymethane. The anomeric effect revisited

Abstract: The conformational energy map for the rotamers of dimethoxymethane has been calculated using both the 3-21G and 6-31G* basis sets with complete geometry optimization in each case. Higher level calculations including electron correlation also have been performed on selected rotamers. At larger torsional angles, the map has approximate 4-fold symmetry, and this symmetry may be used to quantify the difference in the interactions in the (+sc, {minus}sc) and (+sc, +sc) regions. Large changes in bond angles were found, and the dipole moment also changed considerably on C-O bond rotation. Calculations on equatorial and axial 2-methoxytetrahydropyran show that the axial form is favored by 1.33 kcal/mol, in fair agreement with experiment. Calculations also were carried out on the two lowest energy forms of 1,1-dimethoxyethane and on five forms of methyl propyl ether. Consideration of all these data indicates that the anomeric stabilization in dimethoxymethane is much greater than in sterically more congested systems, but the stabilization of 1,1-dimethoxyethane is similar to that of 2-methoxytetrahydropyran and other acetals.

A dynamic model for the structure of acyl carrier protein in solution.

Abstract: The determination of solution structures of proteins using two-dimensional NMR data is commonly based on the assumption that the structure can be represented by a single rigid conformer. We present here a procedure whereby this assumption can be relaxed and illustrate its application to acyl carrier protein from Escherichia coli, a small negatively charged protein with no internal disulfide bonds. The methodology rests on a model having two distinct conformers in dynamic equilibrium. Use of this two-state model results in a dramatic improvement in fit to cross-relaxation-derived distance constraints and a substantial lowering of molecular mechanics energies for individual conformers of acyl carrier protein. The two-state model retains the three-helix motif previously identified on the basis of a one-state structure, but substantial motion of loop regions and the C-terminal peptide, as well as partial disruption of the second helix, is suggested to occur. Support for the existence of these motions can be found in amide exchange rate and spin relaxation time data.

Directional electron transfer: conformational interconversions and their effects on observed electron-transfer rate constants

Abstract: The interaction between conformation changes and electron-transfer rates is considered for systems containing two redox centers. The effect of conformation changes on the free-energy barrier to intramolecular electron transfer is examined. Unstable conformers R* of the reactant (or P* of the product) that are either more (low-{lambda} intermediates) or less (high-{lambda} intermediates) redox-active than the stable reactant R (or product P) are considered. The relative energies of the conformers determine whether the observed electron-transfer reaction proceeds by a two-step mechanism involving the intermediate formation of an unstable conformer or by a direct (concerted) reaction involving only the stable reactant and product. The present analysis generates a set of equations that indicate when the two-step or the direct mechanism is energetically favored. Only when the two-step mechanisms are favored is gating or conformational control possible.

Ab initio studies on silicon compounds. 2. On the gauche structure of the parent polysilane

Abstract: Ab initio crystal orbital calculations are performed on the electronic structures of the parent polysilane. The analysis of the energy band structure and the rotational potential in terms of the trans-gauche conformational transitions is examined. It is found that the trans conformer is the ground state of the polysilane. The gauche-polysilane (GP) is 0.15 kcal/mol per SiH 2 unit above the trans-polysilane (TP). TP has a smaller band gap, lower ionization potential and greater electron delocalization than GP. All the results suggest that the conservation of near trans conformation is important in the improvement of the semiconductor characteristics of polysilanes

s-cis and s-trans Conformers of formic, thioformic and dithioformic acids. An ab initio study

Abstract: Ab initio SCF-MO calculations have been carried out for formic, thioformic and dithioformic acids using the 6–31G* basis set. Fully optimized geometries, atomic charges, relative stabilities and harmonic force fields for s-cis and s-trans conformers of these molecules have been determined and the effects of oxygen-by-sulphur substitution analysed. A realistic description of the molecular charge distribution can be reached by introducing a quantum-mechanical correction to the Mulliken atomic charges, derived from the ‘charge’-‘charge flux’-‘overlap’(CCFO) model. Unlike reported theoretical results, the present ab initio calculations yield relative stabilities of the thioformic acid conformers in agreement with experiment [s-cis(thiol) > s-trans(thiol) > s-cis(thione) > s-trans(thione)]. The success of these ab initio calculations should be partially ascribed to the inclusion of polarization functions on all non-hydrogen atoms.

Relaxed potential energy surfaces of maltose

Abstract: Experimentally observed solution conformations of carbohydrate molecules might correspond to a dynamical average of several interconverting conformers in solution. In order to understand and describe more precisely molecular flexibility and motions, new computational routes have to be envisaged. Compared to conventional approaches where sugar residues are treated as rigid, the optimization of all the internal parameters—i.e., bond angles, valence angles, and all torsional angles—is an important step toward more realistic information. Here we report the calculations of potential energy surfaces where all the internal coordinates of the molecules were “relaxed” and minimized through an extensive molecular mechanics scheme. For this work, a prototypical carbohydrate system, the disaccharide α-maltose, was selected. The inclusion of the relaxed principle into conformational description of maltose does not generally alter the overall shape of the allowed low-energy regions, or the position of the local minima. However, flexibility within the ring plays a crucial role. Its principle effect is the lowering of energy barriers to conformational transitions about the glycosidic bonds, permitting pathways among the low-energy minima. This occurs with retaining the overall 4C1 conformation of the glucose residues. The torsional angles corresponding to the orientations of the hydroxyl groups, especially the primary hydroxyl ones, display stable arrangements separated by energy barriers. They create subpopulations of stable conformers and it has not been possible to take into consideration interconversion of one subpopulation to another one. A “synthetic” relaxed potential energy surface is proposed, which can provide a realistic starting base for further investigation of solution behavior of dynamic simulations.

Kinetics of the purified glucose transporter. Direct measurement of the rates of interconversion of transporter conformers.

Abstract: There is considerable evidence that the mechanism of glucose transport by the transporter of human erythrocytes is one in which the transporter oscillates between two conformations, To and Ti. Each conformer possesses a single glucose binding site that in vivo faces either the extracellular space (conformer To) or the cytoplasm (conformer Ti). In this study, the interconversions of these conformers in the absence and presence of D-glucose have been directly observed by means of the stopped-flow method with fluorescence detection. Nearly unidirectional conversion of one conformer to the other was accomplished by rapidly mixing purified transporter (a mixture of To and Ti) with either 4,6-ethylidene-D-glucose, which preferentially binds to To, or phenyl beta-D-glucoside, which preferentially binds to Ti. The values of the individual rate constants for the conversion of Ti to To and vice versa in the absence and presence of D-glucose at 10.0 degrees C have been obtained, and these show that the kinetics are consistent with the alternating conformation model for transport. Conformational change occurs much more rapidly with glucose bound to the transporter. Furthermore, the activation energy Ea for conformer interconversion is much less when glucose is bound than for unliganded transporter. For example, Ea is approximately 28 kcal/mol for Ti----To versus 17 kcal/mol for Ti + S----ToS, where S is glucose. The alpha-anomer of glucose was 37% more effective than the beta-anomer in speeding the interconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Abstract: Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

Determination of the geometry of deuterated tryptamine by rotationally resolved electronic spectroscopy

Abstract: The low and high resolution fluorescence excitation spectra of d3‐tryptamine have been observed in the environment of a cold, supersonic molecular beam. As in the case of h3‐tryptamine, six bands due to the origins of different conformers have been found in the low resolution spectrum of deuterated tryptamine. A previous paper reported that conformers labeled A and B and conformers labeled D and E of tryptamine have identical rotational structures. However, for deuterated tryptamine those conformers have distinguishable rotational structures. Analysis of the rotational structure in the high resolution electronic spectra of five of the bands was used to determine the geometries of the different conformers. Conformers A, B, and F have a gauche conformation with respect to the rotation about the Cα–Cβ bond while conformers D and E have an eclipsed conformation. The geometries of conformers A and B and conformers D and E differ only in the orientation of the amino group. In these structures the angles of the internal rotation of the amino group are 180°, 60°, 180°, 60°, and −60° for conformers A,B, and D–F, respectively. Feature C consists of two overlapped conformers, and it is suggested that these conformers have the amino group trans to the indole ring.

On the Conformational Isomers in Tetra-O-alkylcalix[4]arenes

Abstract: p-t-Butylcalix[4]arene (14H) was alkylated with RX (R = Me, Et, Pr, and Bu) and the products (14R) were analyzed by HPLC and 1H NMR. It was found that (i) ring inversion arising from the oxygen-through-the-annulus rotation can be inhibited by R greater than Et, (ii) “cone” and “partial cone” result in a 1:1 ratio, and (iii) thermodynamically, the “partial cone” conformation is most stable.

Liquid crystalline polyethers based on conformational isomerism. 2. Thermotropic polyethers and copolyethers based on 1-(4-hydroxyphenyl)-2-(2-methyl-4-hydroxyphenyl)ethane and flexible spacers containing an odd number of methylene units

Abstract: Le nombre d'unites methylene est de 5, 7, 9 et 11. Polyetherification catalysee par transfert de phase

Solution conformation of conotoxin GI determined by 1H nuclear magnetic resonance spectroscopy and distance geometry calculations

Abstract: Conformational analysis of conotoxin GI, one of the neurotoxic peptides produced by a marine snail, genus Conus, was performed by a combination of nuclear magnetic resonance spectroscopy (NMR) and distance geometry calculations. The resulting conformers on minimization of the target function were classified into two groups. The difference in the structures of the conformers is mainly due to the difference in the orientation of the side chain of the tyrosyl residue. The results show that the solution structure of conotoxin GI satisfies the conformational requirements for the biological activity of an antagonist toward nicotinic cholinergic receptors elucidated in a series of studies on alkaloids. The structure is discussed on the basis of the results of comparison of the atomic arrangements of the active sites of snake venom peptides and molecular models based on the results of secondary structure prediction.

Conformational Analysis of Didemnins. A multidisciplinary approach by means of X-Ray, NMR, molecular-dynamics, and molecular-mechanics techniques

Abstract: We present the application of several homo- and heteronuclear 1D- and 2D-NMR techniques to assign the 1H-NMR chemical shifts of the dominant conformation of didemnin B (2; three different conformations in (D6)DMSO solution in the ratio 8:1:1) and its conformational analysis, as well as the solution conformation of didemnin A (1). The conformations were refined by restrained molecular-dynamics calculations using the GROMOS program and by MOMO, a novel personal-computer-based interactive molecular-graphics and molecular-mechanics package, using experimental distances (via a H…H pseudo potential function) as restraints. The solution structures of 1 and 2 obtained by GROMOS and MOMO calculations were compared with each other and related to the recently solved crystal structure of 2. Focusing on the main conformer, the two kinds of the distance-restrained conformational calculations for 2 yielded a ‘solution structure’ close to the crystal structure. Almost all of the 40 restrained H…H distances coincided (within the estimated standard deviations) with those observed in the crystal structure. One more hydrogen bond was detected in solution involving the lactoyl OH group (disordered in the crystal structure) and the dimethyltyrosine (Me2Tyr5) carbonyl O-atom. The macrocyclic ring system in the modeled solution structure of 1 exhibited a topology close to those of the solution and crystal structures of 2. The main difference between 1 and 2 could be traced back to a significant change in the Ψ angle of the N-methyl-D-leucine (MeLeu7) residue. In 1, the N-methyl moiety of MeLeu7 points inward within the macrocyclic ring toward the 1st and Hip region. We also tested the suitability of structures obtained from NMR data as ‘search fragments’ in the ‘Patterson search approach’ of crystal-structure analysis. It proved possible to resolve the crystal structure of 2 a posteriori with the Patterson search program PATSEE, in this way.

Raman and infrared spectra, conformational stability and Ab initio calculations for n‐propylamine

Abstract: The Raman (3500–10 cm−1) and infrared (3500–50 cm−1) spectra of gaseous and solid n-propylamine, CH3CH2CH2NH2, and its deuterated analog, CH3CH2CH2ND2, were recorded. Additionally, the Raman spectra of the liquids were measured and qualitative depolarization values were obtained. From the fact that several distinct Raman lines disappear on goning from the fluid phases to the solid state, it is concluded that the molecule exists as a mixture of several conformers, with the trans–trans conformer being the most stable form in the solid. The first term indicates the position of the methyl group relative to the CN bond, whereas the second term indicates the position of the lone electron pair on the nitrogen relative to the central CC bond. Relying mainly on group frequencies, depolarization data and relative intensities of Raman and infrared bands, a complete vibrational assignment is proposed for the trans–trans conformer. Ab initio calculations were carried out on these molecules, employing both 3–21G and 6–31G* basis sets. The results obtained using these basis sets are compared, and used in normal coordinate calculations. The results of the ab initio calculations support the vibrational assignment, and also indicate that it is the trans–trans and trans–gauche conformers which are the more stable forms of n–propylamine and have nearly equal energies.

An AB initio structural investigation of 1,3-butadiene, isoprene and 2,3-dimethyl-1,3-butadiene rotamers

Abstract: The variation in the torsional angles of the high energy gauche conformers of 1,3-butadiene, 2-methyl-1, 3-butadiene (isoprene) and 2,3-dimethyl-1,3-butadieneare investigated using geometry optimizations at the HF/6-31G and HF/6-31G* levels. In each case, comparisons are made with the corresponding cis structures. The effects of electron correlation are explored in the case of 1,3-butadiene by including geometry optimizations at the MP2/6-31G* level for both the gauche and cis conformers and for isoprene with single point MP2 and MP3/6-31G*//HF/6-31G* calculations. In all cases, the gauche conformers are found to be more stable than the corresponding cis conformers.

1H-NMR studies of receptor-selective substance P analogues reveal distinct predominant conformations in DMSO-d6.

Abstract: Proton nmr parameters are reported for DMSO-d6 solutions of two receptor-selective substance P analogues: Ac[Arg6,Pro9]SP6-11, which is selective for the NK-1 (SP-P) receptor and [pGlu6,N-MePhe8]SP6-11, which selectively activates the NK-3 (SP-N) receptor. Full peak assignments of both analogues were obtained by COSY experiments. The chemical shifts, coupling constants, and temperature coefficients of amide proton chemical shifts as well as NOESY effects and calculated side-chain rotamer populations of Phe side chains are reported for both peptides. Analysis of coupling constants and temperature coefficients together with the nuclear Overhauser enhancement spectroscopy effects suggest that Ac[Arg6,Pro9]SP6-11 has a trans configuration about the Phe8-Pro9 amide bond and the preferred conformation of this analogue has a type I beta-turn. The nmr data for [pGlu6,N-MePhe8]SP6-11 suggest that this peptide exists as a mixture of cis-trans isomers in which the cis isomer can preferably adopt a type VI beta-turn conformation, and the trans isomer can adopt a gamma-turn conformation. There are indications that the two last turns are stabilized by a hydrogen bond between the syn carboxamide proton and the pGlu ring carbonyl.

Solution conformation of the type I collagen alpha-1 chain N-telopeptide studied by 1H NMR spectroscopy.

Abstract: The solution conformation of the type I collagen alpha-1 chain N-telopeptide has been studied by CD and 1H NMR spectroscopy at 600 MHz in CD3OH/H2O (60/40 v/v) and H2O solutions The 19 amino acids form the N-terminal end of the alpha-1 polypeptide chain By the combined application of several two-dimensional, phase-sensitive NMR techniques (COSY, RELAY, ROESY), a complete assignment of all proton resonances was achieved, and the conformation of the backbone could be established on the basis of the coupling constant and NOE data In CD3OH/H2O solutions the spectroscopic evidence clearly indicates that two sections of the molecule (pE1-Y6 and T11-M19) are extended and that the D7-S10 segment forms a beta-turn, stabilized by a hydrogen bond between NH(S10) and CO(D7) The data suggest that the turn is of the type I kind (minor) and that it coexists with an extended structure (major conformer) Interactions between the two extended parts of the peptide were not observed, thus excluding the existence of a beta-sheet In H2O solution the conformation is significantly different, with no beta-turn, but a completely extended structure is observed

Concerning interconversion of rotamers of trans-1,2-diarylethylenes in the triplet state

Abstract: The applicability of the NEER (non-equilibration of excited rotamers) hypothesis to the lowest triplet state of trans -1,2-diarylethylenes is investigated theoretically in the light of recent triplet-related experimental findings. CS-INDO CI calculations indicate that in the T 1 state the barrier hindering interconversion of rotamers is rather high, 11 – 13 kcal mol −1 , for stilbene and its naphthyl analogues, but decreases to about 6 kcal mol −1 in anthryl analogues, such as 2-styrylanthracene (2-StA), in consequence of considerable localization of the triplet excitation on the anthracene moiety. This suggests that, in fluid solutions, triplet rotamers of 2-StA and related compounds may interconvert during their fairly long lifetime. In highly viscous solutions the viscosity barrier to interconversion is much higher, impeding such an interconversion. The existence of solvent viscous drag, in addition to the theoretically predicted barriers in the triplet state, explains the experimental results in a wide range of temperatures and viscosities.

Stereochemical studies on protonated bridgehead amines. ^1H NMR determination of cis and trans B-C ring-fused structures for salts of hexahydropyrrolo [2,1-a] isoquinolines and related C ring homologs. Capture of unstable ring-fused structures in the solid state

Abstract: Acid-addition salts of tricyclic isoquinolines 2a/b, 3a/b, 4a-4c, 5, 6a/b, 7, 8a/b, 9a/b, and 17a/b were studied by high-field ^1H NMR in CDCl_3 solution. Cis (e.g., 14 and 15 in Figure 1) and trans (e.g., 13)B-C ring-fused structures were identified by using the vicinal ^3J(CH-NH) coupling constants, which demonstrate a Karplus-like behavior. In some cases, we initially observed a trans form, which converted to a cis A form by N H proton exchange. For 4c.HBr, the exchange process was slowed by addition of trifluoroacetic acid. In many cases, cis A and cis B structures were preferred in solution. The pendant phenyl group exerted a strong influence on the preferred solution structure. Observation of the initial, unstable trans-fused structures was related to their capture in the solid state and release intact on dissolution. X-ray diffraction was performed on the HBr salts of 2a (B-C cis), 2b (B-C cis), and 4c (B-C trans). The result for 4c.HBr confirmed the connection between the initial trans form in solution and the solid state. For 17b.HCI two conformers, associated with hindered rotation about the bond connecting the 2,6-disubstituted phenyl group to the tricyclic array, were detected at ambient probe temperature; however, rotamers were not observed for either of the two forms (trans and cis A) of 17a.HBr. Two conformers were also found for 16b.HBr. Temperature-dependent behavior was recorded in the ^1H NMR spectra of 17b.HBr and 16b.HBr; the activation free energy for interconversion of conformers was estimated to be in the vicinity of 17 kcal/mol for the former and 14-15 kcal/mol for the latter. The ^1H NMR spectrum of butaclamol hydrochloride (20.HC1), a potent neuroleptic agent, in Me_2SO-d_6 revealed two species in a ratio of 81:19, which were assigned as trans and cis A forms, respectively. ^1H NMR data for various free bases are also presented and discussed. Empirical force field calculations on three model hydrocarbons are discussed from a perspective of finding an explanation for the configurational/conformational behavior of the bridgehead ammonium salts. Diverse literature examples of structures for protonated bridgehead amines are also discussed. A tentative rationale is suggested for the preference of cis A forms in some protonated tetrahydroisoquinoline derivatives.

Conformational analysis of organic carbonyl compounds. Part 11. Conformational properties of difuryl, dithienyl, and furyl thienyl ketones studied by X-ray crystallography, n.m.r. lanthanide-induced shifts and ab-initio MO calculations

Abstract: The conformational properties of the diheteroaryl ketones of the furan and thiophene series have been studied both experimentally, in the solid state and in solution, and with a theoretical ab-initio approach. X-Ray analysis of the samples which are solid at room temperature was possible only for the compounds which gave suitable crystals, i.e. di(2-thienyl) ketone (2), di(3-thienyl) ketone (5), 2-furyl 3-furyl ketone (7), 2-thienyl 3-thienyl ketone (8) and 3-furyl 2-thienyl ketone (10). The crystal data are: (2) space group F dd2, a= 13.267(2), b= 21.853(4), c= 6.067(1)A, Z= 8, R= 0.0637 for 388 observed reflections; (5) space group P21/n, a= 6.174(1), b= 11.184(3), c= 13.203(2)A, Z= 4, R= 0.0776 for 1 202 observed reflections; (7) space group P21/c, a= 9.900(4), b= 10.934(6), c= 7.485(2)A, Z= 4, R= 0.0461 for 984 observed reflections; (8) space group P21/c, a= 6.183(1), b= 11.109(1), c= 13.379(2)A, Z= 4, R= 0.0732 for 1 186 observed reflections; (10) space group P, a= 13.799(2), b= 10.039(2), c= 6.084(1)A, Z= 4, R= 0.0639 for 1 973 observed reflections. The crystal structures of compounds (5) and (8) are disordered: for the former the disorder concerns the position of one ring, whereas both rings are involved in the latter. For compound (10) the structure of the two crystal lographicaIly independent molecules is the same. From the n,m.r. LIS (lanthanide-induced shifts) measurements (on 1H and 13C) indicative information is obtained on the type of conformer and its relative population present in the solution equilibrium mixture. MO ab-initio calculations, performed by employing the 3-21 G or 3-21 G*(with d-orbitals on the sulphur atom) basis sets for the ground-state conformers of all the molecules considered, show that the solid-state structures are very similar to those calculated for the conformers with the lowestenergy content and the calculated conformer populations are in qualitative agreement with measurements in solution. As a general trend, the solid-state structures, the preferred conformations found in solution and those calculated for the free molecules show that the preferred orientation of one heterocyclic ring with respect to the carbonyl group is of the type found in the corresponding formyl and acetyl derivatives and is maintained in all the diheteroaryl ketones. For the molecules having conformers of similar energy content and different dipole moment, i.e. di(2-furyl) ketone (1), it was demonstrated, on the basis of the classical theory of the solvent effect, that the equilibrium mixture of conformers in the vapour phase is different from that in solution and changes in solvents of different polarity.