Experimental Insights into the Electronic Nature, Spectral Features, and Role of Entropy in Short CH3···CH3 Hydrophobic Interactions.

Hydrophobic interactions are often explored in solution-state aggregation of molecules. However, an experimental electron density description about these interactions is still lacking. Here, we report a systematic study on the electronic nature of methyl···methyl hydrophobic interactions in a series of multicomponent crystals of biologically active molecules. Charge density models based on high-resolution X-ray diffraction allow the visualization of subtle details of electron density features in the interaction region. Our study classifies these interactions as atypical group···group interactions in contrast to σ-hole interactions, which are stabilized by the minimized electrostatic repulsion and maximized dispersion forces. For the first time, we quantified the solid-state entropic contribution from the torsional mode of the methyl groups in stabilizing these interactions by thermal motion analysis based on neutron diffraction as well as variable-temperature crystallography. The carbon atoms in methyl···methyl interactions show a unique upfield chemical shift in the 13C solid-state NMR signal.

Non-Classical Synthons: Supramolecular Recognition by S⋠⋠⋠O Chalcogen Bonding in Molecular Complexes of Riluzole.

Classical examples of supramolecular recognition units or synthons are the ones formed by hydrogen bonds. Here, we report the ubiquity of a S⋅⋅⋅O chalcogen bonded synthon observed in a series of supramolecular complexes of the amyotrophic lateral sclerosis drug riluzole. Although the potential of higher chalcogens such as Se and Te to form robust and directional chalcogen bonded motifs is known, intermolecular sulfur chalcogen bonding is considered to be weak owing to the lower polarizability of S atoms. Here, the robustness and electronic nature of a S⋅⋅⋅O chalcogen bonding non-classical synthon, and the origin of its exceptional directionality have been explored. Bond orders of the drug-coformer chalcogen bonding are found to be as high as one third of a single bond, and they are largely ionic in nature. The contribution of the S⋅⋅⋅O chalcogen bonded motifs to the lattice energies of a series of crystals from the Cambridge Structural Database has been analyzed, showing they can be indeed significant, especially in molecules devoid of strong hydrogen bond donor groups.

S···O chalcogen bonding in sulfa drugs: insights from multipole charge density and X-ray wavefunction of acetazolamide.

Experimental charge density analysis combined with the quantum crystallographic technique of X-ray wavefunction refinement (XWR) provides quantitative insights into the intra- and intermolecular interactions formed by acetazolamide, a diuretic drug. Firstly, the analysis of charge density topology at the intermolecular level shows the presence of exceptionally strong interaction motifs such as a DDAA-AADD (D-donor, A-acceptor) type quadruple hydrogen bond motif and a sulfonamide dimer synthon. The nature and strength of intra-molecular S···O chalcogen bonding have been characterized using descriptors from the multipole model (MM) and XWR. Although pure geometrical criteria suggest the possibility of two intra-molecular S···O chalcogen bonded ring motifs, only one of them satisfies the "orbital geometry" so as to exhibit an interaction in terms of an electron density bond path and a bond critical point. The presence of 'σ-holes' on the sulfur atom leading to the S···O chalcogen bond has been visualized on the electrostatic potential surface and Laplacian isosurfaces close to the 'reactive surface'. The electron localizability indicator (ELI) and Roby bond orders derived from the 'experimental wave function' provide insights into the nature of S···O chalcogen bonding.

Organic alloys of room temperature liquids thiophenol and selenophenol.

The first examples of organic alloys of two room temperature liquids, obtained and characterized via in situ cryo-crystallography, are presented. Thiophenol and selenophenol, which exhibit isostructurality and similar modes of S⋯S and Se⋯Se homo-chalcogen interactions along with weak and rare S­H⋯S and Se­H⋯Se hydrogen bonds, are shown to form solid solutions exhibiting Veggard's law-like trends.

Unusually short chalcogen bonds involving organoselenium: insights into the Se-N bond cleavage mechanism of the antioxidant ebselen and analogues.

Structural studies on the polymorphs of the organoselenium antioxidant ebselen and its derivative show the potential of organic selenium to form unusually short Se⋅⋅⋅O chalcogen bonds that lead to conserved supramolecular recognition units. Se⋅⋅⋅O interactions observed in these polymorphs are the shortest such chalcogen bonds known for organoselenium compounds. The FTIR spectral evolution characteristics of this interaction from solution state to solid crystalline state further validates the robustness of this class of supramolecular recognition units. The strength and electronic nature of the Se⋅⋅⋅O chalcogen bonds were explored using high-resolution X-ray charge density analysis and atons-in-molecules (AIM) theoretical analysis. A charge density study unravels the strong electrostatic nature of Se⋅⋅⋅O chalcogen bonding and soft-metal-like behavior of organoselenium. An analysis of the charge density around Se-N and Se-C covalent bonds in conjunction with the Se⋅⋅⋅O chalcogen bonding modes in ebselen and its analogues provides insights into the mechanism of drug action in this class of organoselenium antioxidants. The potential role of the intermolecular Se⋅⋅⋅O chalcogen bonding in forming the intermediate supramolecular assembly that leads to the bond cleavage mechanism has been proposed in terms of electron density topological parameters in a series of molecular complexes of ebselen with reactive oxygen species (ROS).

Experimental validation of 'pnicogen bonding' in nitrogen by charge density analysis.

The participation of a nitrogen atom acting as an electrophile in pnicogen bonding, a hitherto unexplored interaction has been established by experimental charge density analysis. QTAIM and NBO analyses ratify this observation.

Exploring cyclopentadienone antiaromaticity: charge density studies of various tetracyclones.

A systematic study of six tetracyclones has been carried out using experimental and theoretical charge density analysis. A three pronged approach based on quantum theory of atoms in molecules (QTAIM), nucleus independent chemical shifts (NICS) criterion, and source function (SF) contributions has been performed to establish the degree of antiaromaticity of the central five-membered ring in all the derivatives. Electrostatic potentials mapped on the isodensity surface show that electron withdrawing substituents turn both C and O atoms of the carbonyl group more electropositive while retaining the direction of polarity.

Concomitant nitrene and carbene insertion accompanying ring expansion: spectroscopic, X-ray, and computational studies.

Reinvestigation of the thermolysis of azido-meta-hemipinate (I) yielded, in addition to known II, unusual products III and IV. These products are formed via a rare intramolecular nitrene insertion into an adjacent methoxy C-H bond followed by an intermolecular reaction during a ring-expansion and a ring-extrusion reaction followed by a carbene insertion. The structures of the new compounds were confirmed using a battery of techniques, including HRMS (ESI-QTOF) and 2D NMR as well as X-ray crystallography for compound IV. Density functional theory methods were used to support the proposed mechanism of formation of the products.

Experimental evidence for 'carbon bonding' in the solid state from charge density analysis.

The validity of the newly proposed 'carbon bonding', an interaction where a carbon atom acts as an electrophilic site towards a variety of nucleophiles, has been investigated in the solid state. X-ray charge density analysis provides experimental evidence for this hitherto unexplored interaction and unravels its nature and strength.

2,2,2-Trichloro-N-(3-nitro-phen-yl)acetamide.

In the title compound, C(8)H(5)Cl(3)N(2)O(3), the dihedral angle between the nitro-phenyl ring and the acetamide group is 5.47 (6)°. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into chains running parallel to the b axis.

(2E)-1-(5-Chloro-thio-phen-2-yl)-3-(2,3-dimeth-oxy-phen-yl)prop-2-en-1-one.

In the title compound, C(15)H(13)ClO(3)S, the chloro-thio-phene and dimeth-oxy-phenyl groups are linked by a prop-2-en-1-one group. The C=C double bond exhibits an E conformation. The mol-ecule is non-planar, with a dihedral angle of 31.12 (5)° between the chloro-thio-phene and dimeth-oxy-phenyl rings. The meth-oxy group at position 3 is coplanar with the benzene ring to which it is attached, with a C-O-C-C torsion angle of -3.8 (3)°. The meth-oxy group attached at position 2 of the benzene ring is in a (+)synclinal conformation, as indicated by the C-O-C-C torsion angle of -73.6 (2)°. In the crystal, two different C-H⋯O inter-molecular inter-actions generate chains of mol-ecules extending along the b axis.

N-H...F hydrogen bonds in fluorinated benzanilides: NMR and DFT study.

Using (19)F and (1)H-NMR (with (14)N decoupling) spectroscopic techniques together with density functional theoretical (DFT) calculations, we have investigated weak molecular interactions in isomeric fluorinated benzanilides. Simultaneous presence of through space nuclear spin-spin couplings ((1h)J(N-HF)) of diverse strengths and feeble structural fluctuations are detected as a function of site specific substitution of fluorine atoms within the basic identical molecular framework. The transfer of hydrogen bonding interaction energies through space is established by perturbing their strengths and monitoring the effect on NMR parameters. Multiple quantum (MQ) excitation, up to the highest possible MQ orders of coupled protons, is utilized as a tool for accurate (1)H assignments. Results of NMR studies and DFT calculations are compared with the relevant structural parameters taken from single crystal X-ray diffraction studies.

Crystal chemistry of the noncentrosymmetric eulytites: A(3)Bi(XO(4))(3) (X = V, A = Pb; X = P, A = Ca, Cd, Sr, Pb).

Eulytite compounds, A(3)Bi(XO(4))(3) (X = P, A = Ca, Cd, Sr, Pb), belong to the noncentrosymmetric space group I4̅3d (No. 220) as determined by single-crystal X-ray diffraction studies. The crystals were grown from the melt-cool technique with considerable difficulty as the compounds melt incongruently at their melting temperature, except for the compound Pb(3)Bi(PO(4))(3). The unit cell parameter a is 9.984(5), 9.8611(3), 10.2035(3), and 10.3722(2) Šfor Ca(3)Bi(PO(4))(3), Cd(3)Bi(PO(4))(3), Sr(3)Bi(PO(4))(3), and Pb(3)Bi(PO(4))(3) respectively, and there are four formula units in the unit cell. The structure of Pb(3)Bi(VO(4))(3), a unique eulytite with vanadium substitution, is compared with all these phosphorus substituted eulytites. The A(2+) and Bi(3+) cations occupy the special position (16c) while the O anions occupy the general Wyckoff position (48e) in the crystal structure. Only one O position has been identified for Pb(3)Bi(PO(4))(3) and Pb(3)Bi(VO(4))(3), whereas two O atom sites were identified for Ca(3)Bi(PO(4))(3), Cd(3)Bi(PO(4))(3), and Sr(3)Bi(PO(4))(3). The UV-vis diffuse reflectance spectra indicate large band gaps for all the phosphate eulytites while a lower band gap is observed for the vanadate eulytite. The feasibility of the use of these compounds in optoelectronic devices has been tested by measuring the second-harmonic generation (SHG) values which have been found to be of a magnitude equivalent to the commercially used KDP (KH(2)PO(4)).

4-Azido-methyl-7-methyl-2-oxo-2H-chromene-6-sulfonyl azide.

In the title compound, C(11)H(8)N(6)O(4)S, the plane of the coumarin aromatic ring is twisted by 17.2 (2)° with respect to the plane of the azide group bound to the methyl-ene substituent, whereas it is twisted by 83.2 (2)° to the plane of the azide attached to the sulfonyl group. The crystal structure is stabilized by weak C-H⋯O inter-actions, leading to the formation of dimers with R(2) (2)(12) graph-set motifs. These dimers are further linked by weak S-O⋯π and π-π contacts [centroid-centroid distance = 3.765 (2) Å], leading to the formation of a layered structure.

Proton NMR studies of dihalogenated phenyl benzamides: two-dimensional higher quantum methodologies.

The scalar coupled proton NMR spectra of many organic molecules possessing more than one phenyl ring are generally complex due to degeneracy of transitions arising from the closely resonating protons, in addition to several short- and long-range couplings experienced by each proton. Analogous situations are generally encountered in derivatives of halogenated benzanilides. Extraction of information from such spectra is challenging and demands the differentiation of spectrum pertaining to each phenyl ring and the simplification of their spectral complexity. The present study employs the blend of independent spin system filtering and the spin-state selective detection of single quantum (SQ) transitions by the two-dimensional multiple quantum (MQ) methodology in achieving this goal. The precise values of the scalar couplings of very small magnitudes have been derived by double quantum resolved experiments. The experiments also provide the relative signs of heteronuclear couplings. Studies on four isomers of dihalogenated benzanilides are reported in this work.

Apparent shortening of the Csp(3)-Csp(3)bond analysed via a variable-temperature X-ray diffraction study in racemic 1,1'-binaphthalene-2,2'-diyl diethyl bis(carbonate).

Crystal structure determination at room temperature [292 (2) K] of racemic 1,1'-binaphthalene-2,2'-diyl diethyl bis(carbonate), C(26)H(22)O(6), showed that one of the terminal carbon-carbon bond lengths is very short [Csp(3)-Csp(3) = 1.327 (6) A]. The reason for such a short bond length has been analysed by collecting data sets on the same crystal at 393, 150 and 90 K. The values of the corrected bond lengths clearly suggest that the shortening is mainly due to positional disorder at two sites, with minor perturbations arising as a result of thermal vibrations. The positional disorder has been resolved in the analysis of the 90 K data following the changes in the unit-cell parameters for the data sets at 150 and 90 K, which appear to be an artifact of a near centre of symmetry relationship between the two independent molecules in the space group P1 at these temperatures. Indeed, the unit cell at low temperature (150 and 90 K) is a supercell of the room-temperature unit cell.

Discerning the degenerate transitions of scalar coupled 1H NMR spectra: correlation and resolved techniques at higher quantum.

The blend of spin topological filtering and the spin state selective detection of single quantum transitions by the two dimensional multiple quantum-single quantum correlation and higher quantum resolved techniques have been employed for simplifying the complexity of scalar coupled (1)H NMR spectra. The conventional two dimensional COSY and TOCSY experiments, though identify the coupled spin networks, fail to differentiate them due to severe overlap of transitions. Non-selective excitation of homonuclear higher quantum of protons results in filtering of spin systems irrespective of their spin topologies. The spin state selection by passive (19)F spins provides fewer transitions in each cross section of the single quantum dimension simplifying the analyses of the complex spectra. The degenerate single quantum transitions are further discerned by spin selective double and/or triple quantum resolved experiments that mimic simultaneous heteronuclear and selective homonuclear decoupling in the higher quantum dimension. The techniques aided the determination of precise values of spectral parameters and relative signs of the couplings.

4-Chloro-N-(3-chloro-phen-yl)benzamide.

The title compound, C(13)H(9)Cl(2)N, has an intra-molecular C-H⋯O close contact, and presents the NH group syn to the meta-chloro group in the aniline ring and trans to the C=O group. The crystal packing is formed by infinite chains of N-H⋯O hydrogen bonds along the c axis. Cl⋯Cl [3.474 (1) Å] contacts link chains. The crystal used for data collection was a twin, the domains related by the twin law 0.948 (1)/0.052 (1).

Ethyl 4-(4-hydroxy-phen-yl)-6-methyl-2-oxo-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate monohydrate.

In the title compound, C(14)H(16)N(2)O(4)·H(2)O, the dihedral angles between the planes of the 4-hydroxy-phenyl and ester groups with the plane of the six-membered tetra-hydro-pyrimidine ring are 87.3 (1) and 75.9 (1)°, respectively. The crystal structure is stabilized by O-H⋯O and N-H⋯O hydrogen bonding between the water mol-ecule and the organic functionalities.

Ethyl 4-(4-chloro-phen-yl)-6-methyl-2-thioxo-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

In the title compound, C(14)H(15)ClN(2)O(2)S, the tetra-hydro-pyrimidine ring adopts a twisted boat conformation with the carbonyl group in an s-trans conformation with respect to the C=C double bond of the six-membered tetra-hydro-pyrimidine ring. The mol-ecular conformation is determined by an intra-molecular C-H⋯π inter-action. The crystal structure is further stabilized by inter-molecular N-H⋯O mol-ecular chains and centrosymmetric N-H⋯S dimers.