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.

Supramolecular interactions in carboxylate and sulfonate salts of 2,6-diamino-4-chloropyrimidinium.

Two new salts, namely 2,6-diamino-4-chloropyrimidinium 2-carboxy-3-nitrobenzoate, C4H6ClN4+·C8H4NO6-, (I), and 2,6-diamino-4-chloropyrimidinium p-toluenesulfonate monohydrate, C4H6ClN4+·C7H7O3S-·H2O, (II), have been synthesized and characterized by single-crystal X-ray diffraction. In both crystal structures, the N atom in the 1-position of the pyrimidine ring is protonated. In salt (I), the protonated N atom and the amino group of the pyrimidinium cation interact with the carboxylate group of the anion through N-H...O hydrogen bonds to form a heterosynthon with an R22(8) ring motif. In hydrated salt (II), the presence of the water molecule prevents the formation of the familiar R22(8) ring motif. Instead, an expanded ring [i.e. R32(8)] is formed involving the sulfonate group, the pyrimidinium cation and the water molecule. Both salts form a supramolecular homosynthon [R22(8) ring motif] through N-H...N hydrogen bonds. The molecular structures are further stabilized by π-π stacking, and C=O...π, C-H...O and C-H...Cl interactions.

Supramolecular architectures in two 1:1 cocrystals of 5-fluorouracil with 5-bromothiophene-2-carboxylic acid and thiophene-2-carboxylic acid.

In solid-state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5-fluorouracil (5FU; systematic name: 5-fluoro-1,3-dihydropyrimidine-2,4-dione), namely 5-fluorouracil-5-bromothiophene-2-carboxylic acid (1/1), C5H3BrO2S·C4H3FN2O2, (I), and 5-fluorouracil-thiophene-2-carboxylic acid (1/1), C4H3FN2O2·C5H4O2S, (II), have been synthesized and characterized by single-crystal X-ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid-acid R22(8) homosynthon (O-H...O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R22(8) motif] via a pair of N-H...O hydrogen bonds. The crystal structures are further stabilized by C-H...O interactions in (II) and C-Br...O interactions in (I). In both crystal structures, π-π stacking and C-F...π interactions are also observed.

Supramolecular hydrogen-bonding patterns in 1:1 cocrystals of 5-fluorouracil with 4-methylbenzoic acid and 3-nitrobenzoic acid.

The design of a pharmaceutical cocrystal is based on the identification of specific hydrogen-bond donor and acceptor groups in active pharmaceutical ingredients (APIs) in order to choose a `complementary interacting' molecule that can act as an efficient coformer. 5-Fluorouracil (5FU) is a pyrimidine derivative with two N-H donors and C=O acceptors and shows a diversity of hydrogen-bonding motifs. Two 1:1 cocrystals of 5-fluorouracil (5FU), namely 5-fluorouracil-4-methylbenzoic acid (5FU-MBA), C4H3FN2O2·C8H8O2, (I), and 5-fluorouracil-3-nitrobenzoic acid (5FU-NBA), C4H3FN2O2·C7H5NO4, (II), have been prepared and characterized by single-crystal X-ray diffraction. In (I), the MBA molecules form carboxylic acid dimers [R22(8) homosynthon]. Similarly, the 5FU molecules form two types of base pair via a pair of N-H...O hydrogen bonds [R22(8) homosynthon]. In (II), 5FU interacts with the carboxylic acid group of NBA via N-H...O and O-H...O hydrogen bonds, generating an R22(8) ring motif (heterosynthon). Furthermore, the 5FU molecules form base pairs [R22(8) homosynthon] via N-H...O hydrogen bonds. Both of the crystal structures are stabilized by C-H...F interactions.

Crystal structure and hydrogen-bonding patterns in 5-fluoro-cytosinium picrate.

In the crystal structure of the title compound, 5-fluoro-cytosinium picrate, C4H5FN3O+·C6H2N3O7-, one N heteroatom of the 5-fluoro-cytosine (5FC) ring is protonated. The 5FC ring forms a dihedral angle of 19.97 (11)° with the ring of the picrate (PA-) anion. In the crystal, the 5FC+ cation inter-acts with the PA- anion through three-centre N-H⋯O hydrogen bonds, forming two conjoined rings having R21(6) and R12(6) motifs, and is extended by N-H⋯O hydrogen bonds and C-H⋯O inter-actions into a two-dimensional sheet structure lying parallel to (001). Also present in the crystal structure are weak C-F⋯π inter-actions.

Hydrogen-bonding patterns in 5-fluoro-cytosine-melamine co-crystal (4/1).

The asymmetric unit of the title compound, 4C4H4FN3O·C3H6N6, comprises of two independent 5-fluoro-cytosine (5FC) mol-ecules (A and B) and one half-mol-ecule of melamine (M). The other half of the melamine mol-ecule is generated by a twofold axis. 5FC mol-ecules A and B are linked through two different homosynthons [R 2 (2)(8) ring motif]; one is formed via a pair of N-H⋯O hydrogen bonds and the second via a pair of N-H⋯N hydrogen bonds. In addition to this pairing, the O atoms of 5FC mol-ecules A and B inter-act with the N2 amino group on both sides of the melamine mol-ecule, forming a DDAA array of quadruple hydrogen bonds and generating a supra-molecular pattern. The 5FC (mol-ecules A and B) and two melamine mol-ecules inter-act via N-H⋯O, N-H⋯N and N-H⋯O, N-H⋯N, C-H⋯F hydrogen bonds forming R 6 (6)(24) and R 4 (4)(15) ring motifs. The crystal structure is further strengthened by C-H⋯F, C-F⋯π and π-π stacking inter-actions.

Nanocomposite coatings on biomedical grade stainless steel for improved corrosion resistance and biocompatibility.

The 316 L stainless steel is one of the most commonly available commercial implant materials with a few limitations in its ease of biocompatibility and long-standing performance. Hence, porous TiO(2)/ZrO(2) nanocomposite coated over 316 L stainless steels was studied for their enhanced performance in terms of its biocompatibility and corrosion resistance, following a sol-gel process via dip-coating technique. The surface composition and porosity texture was studied to be uniform on the substrate. Biocompatibility studies on the TiO(2)/ZrO(2) nanocomposite coatings were investigated by placing the coated substrate in a simulated body fluid (SBF). The immersion procedure resulted in the complete coverage of the TiO(2)/ZrO(2) nanocomposite (coated on the surface of 316 L stainless steel) with the growth of a one-dimensional (1D) rod-like carbonate-containing apatite. The TiO(2)/ZrO(2) nanocomposite coated specimens showed a higher corrosion resistance in the SBF solution with an enhanced biocompatibility, surpassing the performance of the pure oxide coatings. The cell viability of TiO(2)/ZrO(2) nanocomposite coated implant surface was examined under human dermal fibroblasts culture, and it was observed that the composite coating enhances the proliferation through effective cellular attachment compared to pristine 316 L SS surface.