Carboxamide-pyridine N-oxide heterosynthon for crystal engineering and pharmaceutical cocrystals

The novel carboxamide-pyridine N-oxide synthon, sustained via N-H...O- hydrogen bonding and C-H...O interaction, is shown to assemble isonicotinamide N-oxide in a triple helix architecture and the same heterosynthon is exploited to synthesize cocrystals of barbiturate drugs with 4,4'-bipyridine N,N'-dioxide.     

Strain dependence of the vibrational modes of a diacetylene crystal

Resonance Raman spectroscopy has been used to measure the strain dependence of four high-frequency vibrational modes in a single crystal of toluene sulfonate diacetylene polymer. The 0.62-μm thick crystal was stretched elastically to 4% strain before fracture occurred. This was equivalent to an ultimate tensile strength of 2.0 × 10⁹ N m^?2. The strain dependence of the vibrational modes has been interpreted using a simple point mass and anharmonic spring constant model. A Fermi resonance was observed for two vibrational modes which are degenerate at 2.1% strain and a 1464 cm^?1 frequency.     

ODMR and triplet state kinetics of a carbazolyl substituted diacetylene crystal

Carbazolyl substituted diacetylene (DCH) monomer crystals showing phosphorescence from four traps have been investigated by optically detected magnetic resonance (ODMR) at 1.2 K. These localized triplet states are attributed to the carbazolyl side groups. Their population and depopulation rate constants and zero field splitting parameters (0.097 <|D|< 0.1002 cm^?1; 0.0068 <|E|<0.0105 cm^?1) have been determined. The results suggest that the traps are disturbed substituents. The proposed interaction of the trap states with an exciton band at 23926 cm^?1 is supported by temperature dependent lifetime measurements.     

Experimental observation of exciton surface polaritons on a polymerized diacetylene crystal

Exciton surface polaritons (ESP's) have been observed by the technique of attenuated total reflection (ATR) spectroscopy at 295 K on the (100) face of the polymerized diacetylene crystal poly-2,4-hexadiyne-1,6-diol bis (p-toluene sulfonate). The ATR experiments were performed by measuring the p-polarized reflectivity as a function of angle of incidence at constant wavelength. By changing the wavelength of the exciting light and repeating the angular scans, the experimental dispersion of the surface mode was determined for the wavelength range 632.8 to 596 nm. The intensity of the electromagnetic field in the three regions, prism, gap and sample, was calculated to demonstrate the localization of the ESP at the crystal surface.     

Supramolecular interactions in salts/cocrystals involving pyrimidine derivatives of sulfonate/carboxylic acid

The crystal structures of three compounds involving aminopyrimidine derivatives are reported, namely, 5-fluorocytosinium sulfanilate–5-fluorocytosine–4-azaniumylbenzene-1-sulfonate (1/1/1), C₄H₅FN₃O⁺·C₆H₆NO₃S⁻·C₄H₄FN₃O·C₆H₇NO₃S, I , 5-fluorocytosine–indole-3-propionic acid (1/1), C₄H₄FN₃O·C₁₁H₁₁NO₂, II , and 2,4,6-triaminopyrimidinium 3-nitrobenzoate, C₄H₈N₅⁺·C₇H₄NO₄⁻, III , which have been synthesized and characterized by single-crystal X-ray diffraction. In I , there are two 5-fluorocytosine (5FC) molecules (5FC-A and 5FC-B) in the asymmetric unit, with one of the protons disordered between them. 5FC-A and 5FC-B are linked by triple hydrogen bonds, generating two fused rings [two R₂²(8) ring motifs]. The 5FC-A molecules form a self-complementary base pair [R₂²(8) ring motif] via a pair of N—H…O hydrogen bonds and the 5FC-B molecules form a similar complementary base pair [R₂²(8) ring motif]. The combination of these two types of pairing generates a supramolecular ribbon. The 5FC molecules are further hydrogen bonded to the sulfanilate anions and sulfanilic acid molecules via N—H…O hydrogen bonds, generating R₄⁴(22) and R⁶₆(36) ring motifs. In cocrystal II , two types of base pairs (homosynthons) are observed via a pair of N—H…O/N—H…N hydrogen bonds, generating R₂²(8) ring motifs. The first type of base pair is formed by the interaction of an N—H group and the carbonyl O atom of 5FC molecules through a couple of N—H…O hydrogen bonds. Another type of base pair is formed via the amino group and a pyrimidine ring N atom of the 5FC molecules through a pair of N—H…N hydrogen bonds. The base pairs (via N—H…N hydrogen bonds) are further bridged by the carboxyl OH group of indole-3-propionic acid and the O atom of 5FC through O—H…O hydrogen bonds on either side of the R₂²(8) motif. This leads to a DDAA array. In salt III , one of the N atoms of the pyrimidine ring is protonated and interacts with the carboxylate group of the anion through N—H…O hydrogen bonds, leading to the primary ring motif R₂²(8). Furthermore, the 2,4,6-triaminopyrimidinium (TAP) cations form base pairs [R₂²(8) homosynthon] via N—H…N hydrogen bonds. A carboxylate O atom of the 3-nitrobenzoate anion bridges two of the amino groups on either side of the paired TAP cations to form another ring [R₃²(8)]. This leads to the generation of a quadruple DADA array. The crystal structures are further stabilized by π–π stacking ( I and III ), C—H…π ( I and II ), C—F…π ( I ) and C—O…π ( II ) interactions.     

Spectroscopy and crystal structure of anabasine salts

The anabasinium hydrochloride, hydriodide and perchlorate were characterized by IR and NMR spectroscopy as well as by X-ray diffraction. Anabasinium hydrochloride crystallizes with three independent ionic pairs in the asymmetric part of the orthorhombic unit cell, while anabasinium hydriodide and perchlorate crystals, being isostructural, are hexagonal and contain only one symmetry independent ionic pair. Despite these differences in the crystal data, both types of crystals display very similar helical solid-state patterns. The reported results combined with the CSD searches indicate an inherent tendency of anabasinium salts to crystallize with multiple asymmetric units, and to form folded arrangements in crystals. In the solid state the anabasinium cations predominantly adopt either synperiplanar or antiperiplanar conformations with respect to the mutual orientation of C^*–H and pyridine C–C(N) bonds, with deformations towards, respectively, (+) synclinal or (+) anticlinal rotamers.     

Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids

Cocrystals of the poorly soluble antifungal drug cis-itraconazole (1) with 1,4-dicarboxylic acids have been prepared. The crystal structure of the succinic acid cocrystal with 1 was determined to be a trimer by single-crystal X-ray. The trimer is comprised of two molecules of 1 oriented in antiparallel fashion to form a pocket with a triazole at either end. The extended succinic acid molecule fills the pocket, bridging the triazole groups through hydrogen-bonding interactions rather than interacting with the more basic piperazine nitrogens. The solubility and dissolution rate of some of the cocrystals are approximately the same as those of the amorphous drug in the commercial formulation and are much higher than those for the crystalline free base. The results suggest that cocrystals of drug molecules have the possibility of achieving the higher oral bioavailability common for amorphous forms of water-insoluble drugs while maintaining the long-term chemical and physical stability that crystal forms provide.     

Proton spin-relaxation study of the polymerization of diacetylene in a single crystal

Proton spin-lattice relaxation experiments on the bis-(p-toluenesulfonate) of 2,4-hexadiyne-1,6-diol (TSHD) as a function of temperature (25 to 353 K), of frequency (22 and 44 MHz), and of conversion to polymer were performed to determine the molecular motions in this crystal and to follow the conversion via the changes in the relaxation time T₁. It was found that T₁ is dominated below 125 K by weakly hindered (ΔE = 2.8 kJ/mole) tunneling (Λ = 220 MHz) CH₃ groups, at about 160 K by order-disorder fluctuations around the phase-transition temperature ?_c which depends strongly on the conversion, and above 200 K by the motion of the whole side group. T₁ can be used as sensitive probe for the conversion: The change in T₁ at about 44 K is directly proportional to the conversion, whereas the change at high temperatures (e.g., 353 K) occurs essentially at low conversions (?10%). This is explained by distorted (stressed) areas around the isolated polymer chains, which are estimated to be about 16 times the size of the chains. After an induction period the stresses are relieved by further polymerization.     

Supramolecular chemistry and crystal engineering

Supramolecular chemistry is the chemistry of molecular ensembles and intermolecular interactions. Currently it is a major, interdisciplinary branch of science dealing with chemical, physical, biological and technological aspects of the creation and study of complex chemical systems based upon non-valent interactions. Crystal engineering is a direction of supramolecular chemistry aimed at the design of periodic structures with a desired supramolecular organization. This paper shortly reviews the goals and research objects of supramolecular chemistry and crystal engineering and lists the most important historical facts and the literature.     

Synthesis and X-ray crystal structure of fluorous imidazolium salts

Synthesis of two salts involving CH₂O spacer between the imidazole nitrogen and hexafluoroisopropyl group in the fluorous imidazolium cations is reported. Such an insertion would result in the formation of ??-ammonium ether. The two fluorous imidazolium salts involve one or two -CH₂OCH(CF₃)₂ groups attached to the imidazole nitrogen atoms. These products were synthesized from the reaction between methyimidazole and imidazole as nucleophiles and sevochlorane, ClCH₂OCH(CF₃)₂, as electrophile, in different molar ratios. The resulting products have been characterized by ¹H, ¹³C, and ¹⁹F NMR and FTIR spectroscopy. Also, the single crystal X-ray diffraction analysis for the symmetrically substituted imidazolium product is presented. The preliminary animal tests indicated no anesthetic property but the two tested salts were found to behave as calmative.     

The charge-transfer motif in crystal engineering. Self-assembly of acentric (diamondoid) networks from halide salts and carbon tetrabromide as electron-donor/acceptor synthons

Unusual strength and directionality for the charge-transfer motif (established in solution) are shown to carry over into the solid state by the facile synthesis of a series of robust crystals of the [1:1] donor/acceptor complexes of carbon tetrabromide with the electron-rich halide anions (chloride, bromide, and iodide). X-ray crystallographic analyses identify the consistent formation of diamondoid networks, the dimensionality of which is dictated by the size of the tetraalkylammonium counterion. For the tetraethylammonium bromide/carbon tetrabromide dyad, the three-dimensional (diamondoid) network consists of donor (bromide) and acceptor (CBr(4)) nodes alternately populated to result in the effective annihilation of centers of symmetry in agreement with the sphaleroid structural subclass. Such inherently acentric networks exhibit intensive nonlinear optical properties in which the second harmonics generation in the extended charge-transfer system is augmented by the effective electronic (HOMO-LUMO) coupling between contiguous CBr(4)/halide centers.     

α-Haloacetylene and diacetylene alcohols

Results of investigations of α-haloacetylene and diacetylene alcohols in reactions with various reagents are discussed. Frequently the reactions do not stop at monoadduct formation but are followed by intramolecular cyclization or by rearrangement providing polyfunctional compounds.     

Developments in inorganic crystal engineering

The design and synthesis of crystalline materials through the self-assembly of molecular building blocks and the pursuit of functional materials based upon this approach are usually classified under the banner Crystal Engineering. The field is interdisciplinary in nature involving synthetic, materials, structural and theoretical chemists. There are strong ties to modern crystallography which can offer rapid and accurate structure determination and, in particular, insight into molecular and intermolecular geometries. Illustrative examples that chart the development field and provide an assessment of the current state of the art will be reviewed with an emphasis on inorganic chemistry. Broadly speaking, two classes of compounds will be discussed: those based upon molecules or ions linked into networks via noncovalent interactions and those (coordination polymers) in which metal centres are linked using coordination bonds through bridging ligands into extended networks.     

Physicochemical properties and plastic crystal structures of phosphonium fluorohydrogenate salts

Fluorohydrogenate salts of quaternary phosphonium cations with alkyl and methoxy groups (tetraethylphosphonium (P(2222)(+)), triethyl-n-pentylphosphonium (P(2225)(+)), triethyl-n-octylphosphonium (P(2228)(+)), and triethylmethoxymethylphosphonium (P(222(101))(+))) have been synthesized by the metatheses of anhydrous hydrogen fluoride and the corresponding phosphonium bromide or chloride precursors. The three salts with asymmetric cations, P(222m)(FH)(2.1)F (m = 5, 8, and 101), are room temperature ionic liquids (ILs) and are characterized by differential scanning calorimetry, density, viscosity, and conductivity measurements. Linear sweep voltammetry using a glassy carbon working electrode shows these phosphonium fluorohydrogenate ILs have wide electrochemical windows (>4.9 V) with the lowest viscosity and highest conductivity in the known phosphonium-based ILs. Thermogravimetry shows their thermal stabilities are also improved compared to previously reported alkylammonium cation-based fluorohydrogenate salts. Differential scanning calorimetry and X-ray diffraction revealed that tetraethylphosphonium fluorohydrogenate salt, P(2222)(FH)(2)F, exhibits two plastic crystal phases. The high temperature phase has a hexagonal lattice, which is the first example of a plastic crystal phase with an inverse nickel arsenide-type structure, and the low-temperature phase has an orthorhombic lattice. The high-temperature plastic crystal phase exhibits a conductivity of 5 mS cm(-1) at 50 °C, which is the highest value for the neat plastic crystals.     

Donor-acceptor interactions in crystal engineering

The molecular complex formed between 4-methyltolane and bis(4-N-methylpyridinium)ethyne ditriflate is reported. The X-ray crystal structure indicates that the crystalline superstructure consists of infinite zigzag ribbons of interlocked donor-acceptor complexes separated by triflate counterions.     

Thermotropic liquid crystal behaviour of alkaline-earth-metal dihexadecyl phosphate salts

Alkaline-earth-metal dihexadecyl phosphate salts were synthesized, and their thermal stability was evaluated by thermogravimetry. Their thermotropic liquid crystal behaviour was investigated by differential scanning calorimetry, polarizing optical microscopy, dilatometry, and X-ray diffraction. On heating, the calcium, strontium, and barium salts exhibit columnar liquid crystal phases, whereas the less ionic beryllium and magnesium salts melt directly into isotropic liquids.     

Thermotropic liquid crystal behaviour of alkaline-earth-metal dihexadecyl phosphate salts

Alkaline-earth-metal dihexadecyl phosphate salts were synthesized, and their thermal stability was evaluated by thermogravimetry. Their thermotropic liquid crystal behaviour was investigated by differential scanning calorimetry, polarizing optical microscopy, dilatometry, and X-ray diffraction. On heating, the calcium, strontium, and barium salts exhibit columnar liquid crystal phases, whereas the less ionic beryllium and magnesium salts melt directly into isotropic liquids.     

Preparation, crystal structure, and thermolysis of phenylenediammonium diperchlorate salts

Three salts of phenylenediammonium diperchlorate have been prepared and characterized by X-ray crystallography. Their thermal decomposition has been studied by thermogravimetry (TG), differential thermal analysis (DTA), and explosion delay (DE) measurements. The kinetics of thermal decomposition was evaluated by model fitting and isoconversional methods using TG data. The oxidation-reduction reactions near the surface of thermolysing perchlorates may be responsible for the decomposition followed by explosion. The possible pathways of thermolysis have also been proposed.