Tibor Koritsanszky

Aspherical-atom scattering factors from molecular wave functions. 1. Transferability and conformation dependence of atomic electron densities of peptides within the multipole formalism

In this study, the feasibility of building a database of theoretical atomic deformation density parameters applicable to the construction of the densities of biomacromolecules and to the interpretation of their X-ray diffraction data is discussed. The procedure described involves generation of valence-only structure factors of tripeptides calculated from theoretical densities at the B3LYP level and the refinement of multipole parameters against these simulated data. Our results so far indicate that the backbone pseudoatoms extracted in such a way are highly transferable and fairly invariant with respect to rotations around single bonds in the peptide framework. The ultimate goal is to use the aspherical-atom database for improved macromolecular refinements that are based on high-resolution data and for prediction of electrostatic properties of larger molecules.

Invarioms for improved absolute structure determination of light-atom crystal structures

The determination of molecular absolute configuration from an X-ray analysis for structures that contain only light elements is challenging owing to the weak anomalous dispersion signal. The achievable precision of the Flack x parameter for such structures is therefore limited, especially when the independent-atom model is employed. Invariom modelling can improve this situation. Invarioms are theoretically predicted pseudoatoms within the Hansen & Coppens multipole formalism. They are transferable from one molecule to another and provide generalized aspherical atomic form factors. It is shown that, by application of the invariom approach, the precision and standard uncertainty of the Flack x parameter and therefore the reliability of deducing molecular chirality in an absolute structure determination can be improved.

On the basis-set dependence of local and integrated electron density properties: Application of a new computer program for quantum-chemical density analysis.

A new computer program for post‐processing analysis of quantum‐chemical electron densities is described. The code can work with Slater‐ and Gaussian‐type basis functions of arbitrary angular momentum. It has been applied to explore the basis‐set dependence of the electron density and its Laplacian in terms of local and integrated topological properties. Our analysis, including Gaussian/Slater basis sets up to sextuple/quadruple‐zeta order, shows that these properties considerably depend on the choice of type and number of primitives utilized in the wavefunction expansion. Basis sets with high angular momentum (l = 5 or l = 6) are necessary to achieve convergence for local properties of the density and the Laplacian. In agreement with previous studies, atomic charges defined within Baders Quantum Theory of Atoms in Molecules appear to be much more basis‐set dependent than the Hirshfelds stockholder charges. The former ones converge only at the quadruple‐zeta/higher level with Gaussian/Slater functions.

Fast Experiments for Charge‐Density Determination: Topological Analysis and Electrostatic Potential of the Amino Acids L‐Asn, dl‐Glu, dl‐Ser, and L‐Thr

Synchrotron radiation and CCD detection give the possibility for fast diffraction experiments, which were employed to deduce the exact charge-density distributions of some amino acids. Their topological analysis (the figure shows the negative Laplacian function of dl-serine in the plane of the carboxylate group) yields not only comparable information about intramolecular but also about weak intermolecular interactions.

Experimental charge density studies of disordered N-phenylpyrrole and N-(4-fluorophenyl)pyrrole.

The static electron densities of the title compounds were extracted from high-resolution X-ray diffraction data using the nucleus-centered finite multipole expansion technique. The interpretation of the data collected for the N-phenylpyrrole crystal revealed a static disorder that could be successfully resolved within the aspherical-atom formalism. The local and integrated topological properties of the density obtained via a constrained multipole refinement are in statistical agreement with those calculated at the B3LYP/cc-pVTZ level of theory for the isolated molecule and for those derived from the experimental density of the para-fluorinated derivative N-(4-fluorophenyl)pyrrole. The topological analysis of the densities indicates neither pyramidal character of the pyrrole N-atom nor a quinoidal structure of the phenyl rings in either molecule. The fluorine substitution appears to have only a minor effect on the density of the remaining constituents but it results in markedly different features of the electrostatic potential of the two compounds. The consistency of the multipole refinement is validated by residual density analysis.

Diaryldiacyloxyspirosulfuranes. Part 3. Sulfuranes with five-, six- and seven-membered spirorings: syntheses and molecular structures

Three novel diaryldiacyloxyspirosulfuranes (2–4) with five-, six- and seven-membered spirorings have been prepared, and their molecular structures determined by X-ray diffraction. The structure of spirosulfurane 1 with two identical five-membered spirorings has been reinvestigated. In all spirosulfuranes 1–4 the arrangement of the ligands about the central sulfur atom show a slightly distorted trigonal bipyramidal (TBP) geometry resulting in chiral molecular structure. The axial (hypervalent) S–O and equatorial (covalent) S–Car bond lengths range from 1.838(1) to 1.872(3) and from 1.771 (3) to 1.794(4)A, respectively. The axial O–S–O and equatorial Car–S–Car bond angles lie in the narrow intervals of 174.9(2)–177.4(4)° and 105.8(2)–106.9(2)°, respectively. The five-membered spirorings are practically planar in 1–3. The six-membered spirorings in 2 and 4 assume distorted sofa conformations. The seven-membered spiroring in 3, having four Car atoms with planar configuration, is irregular. The aromatic rings fused with the spirorings are perpendicular to the equatorial plane only if the spiroring is five-membered. In other cases the stable conformations with TBP geometry about sulfur involve a significant torsion of the aromatic ring about the S–Car axis. Thus, in diaryldiacyloxyspirosulfuranes having acyloxy-O ligands at axial positions the structural parameters about the sulfur are not considerably influenced by the shape and size of the spirorings. The O–S–O moiety with hypervalent bonds may be regarded as a structural unity. The sum of the individual S–O bond lengths, (3.684–3.744 A) which is characteristic of diaryldiacyloxyspirosulfuranes, differs markedly from the values found earlier for dialkoxy- and acyloxy-alkyloxy analogues (3.601 and 3.910 A, respectively). For spirosulfurane 3 a rearrangement into the isomeric ten-membered cyclic anhydride 13 is observed.

New Directions in Pseudoatom-Based X-Ray Charge Density Analysis

This chapter revisits critical aspects of pseudoatom interpretation of X-ray Bragg diffraction data to derive the crystalline electron density experimentally. The main focus is on the radial basis functions in the nucleus-centered multipole expansion of the model density. Based on the direct-space projection of the stockholder-partitioned quantum-chemical molecular density onto nucleus-centered spherical harmonics, “bonded-atom” radial functions are derived, in terms of which the original density can be reconstructed. The method allows for a quantitative access of errors introduced by restrictions on the pseudoatom radial functions and for designing more adequate basis sets than those routinely used in the standard model. The applicability of the upgraded multipole formalism to X-ray charge density analysis is demonstrated through pseudoatom fitting of simulated and experimental data. The chemical transferability of stockholder pseudoatoms is analyzed through small-molecule model studies. A protocol to build a stockholder-atom library and the feasibility of simple data-refinement strategies using the databank radial functions is also discussed.

Conformational analysis of thiane-1 imides: an x-ray study of thiane-1-tosylimide and diastereoisomeric 2-alkyl- and 4-phenylthiane-1-tosylimides

Abstract The molecular structures of thiane-1-tosylimide and its cis / trans -2-Me, cis -2-Pr i , trans -2-Bu t and cis / trans -4-Ph derivatives have been investigated by X-ray diffraction. The results confirm our earlier 13 C NMR assignments of configurations, giving direct evidence for ring geometry and conformational preference of ring substituents. They show that the electron-withdrawing tosylimino group is axial in both thiane-1-tosylimide and cis disubstituted analogues, whilst it is equatorial in trans compounds. The C -substituents are always equatorial. Distortions of chair-shaped thiane rings of sulphilimines are compared with those of cyclic sulphoxides and sulphonium salts, and explained by steric effects. Conformations of 1,2-disubstituted thiane-1-imides are controlled by both syn -axial interaction and steric repulsion between 1-tosylimino and 2-alkyl groups, with the latter being the more significant. The conformation of the exocyclic S -tosylimide part is also compared with that of known acyclic N -arylsulphonyl sulphilimines. Rotations about S IV —N, NS VI and S VI C ar bonds are discussed and deviations from S -symmetric conformations and “Koch- Moffitts cases IIa of conjugation” are interpreted in terms of steric effects conjugation, n —σ* type stereoelectronic effects and sulphur(IV)—oxygen interaction; S IV C. S VI N and S VI O bond lengths are discussed on the same basis. The SON sp 2 group may substitute SO 2 in the case “case-IIa of conjugation” with the aryl group. In antiperiplanar position there exists a maximum interaction between the nitrogen lone pair and the S VI O bond, resulting in a significant shortening of the S VI N bond.

Electronic Insight into an Antithrombotic Agent by High‐Resolution X‐Ray Crystallography

Five instead of 200 days measurement time are sufficient (thanks to area detection rather than conventional scintillation detection) to obtain the accurate charge density distribution of an antithrombotic agent with more than 50 atoms by a high-resolution X-ray diffraction experiment. The preferred sites of intermolecular interactions were identified from various topological properties, such as the reactive surface (zero Laplacian function, see picture) and the electrostatic potential.

Molecular structures of cyclic sulfilimines without and with intramolecular sulfur-oxygen interaction: an X-ray study

Abstract 3-Phenylbenzo[1.3.2]dithiazolium ylide 1.1 dioxide (1) and its o-methoxycarbonyl derivative (2) have been prepared and their structures established by X-ray crystallography from diffractometer data. Compound 1 (C12H9NO2S2) crystallizes in the triclinic space group P 1 with a = 6.664(1), b = 7.881(1), c = 12.437(2) A , α = 98.81(1), β = 97.44(1), γ = 113.05(1)°, V = 580.9(4) A 3 , Z = 2, Dc = 1.51 g.cm−3 and μ(CuKα) = 4.00 mm−1. Compound 2 (C14H11NO4S2) crystallizes in the orthorhombic space group P212121, with a = 7.620(1), b = 8.887(1), c = 20.022(2) A , V = 1355.9(5) A 3 , Z = 4, Dc = 1.57 g.cm−3 and μ(CuKα) = 3.65 mm−1. The crystal structures were solved by direct methods and refined to R = 0.062 for 1 and R = 0.028 for 2, using 1663 and 1424 observed reflections, respectively. In the cyclic N-sulfonyl sulfilimines 1 and 2 the characteristic bond distances and bond angles involving S(IV) and S(VI) atoms do not differ significantly from those found earlier for acyclic sulfilimines. Owing to S(IV)…O(carbonyl) close contact the sulfur(IV) atom in 2 exhibits a sulfuran-like configuration with t almost linear (171°) N = S(IV)…O array ( 1.61 + 2.68 = 4.29 A ). The conformations of 1 and 2 have similar features. In both cases the five-membered dithiazolium ring is practically planar and the two aryl rings about sulfur(IV) atom are nearly perpendicular to the CarS(IV)Car plane (“butterfly conformation”). In contrast with acyclic sulfilimines, the benzene ring connected to S9VI) atom is constrained to be coplanar with the S(VI)NS(IV) plane (Koch and Moffitts case I of conjugation).