Protonation Of Nitrogen Atom Research Articles

A 1,3,5-triazine μ3-bridged neutral Cu(I) framework with enhanced stability and CO2 capture selectivity

Compounds with 1,3,5-triazine ring such as melamine derivatives, known for their low cost and high stability, offer potential for affordable, stable metal organic framework (MOF) synthesis. However, reported such frameworks are facing issues like low stability and reduced porosity. To overcome such problems, we explored organic ligands with protonated nitrogen atoms on the 1,3,5-triazine ring, facilitated by introducing hydroxyl groups on carbon atoms of the triazine ring to construct MOFs. By using 5-azacytosine, we have successfully synthesized SXU-121, a neutral ultramicroporous MOF with eta-topology and high density of open Cu(I) sites. SXU-121 features robust structural stability and significant CO2 adsorption capacity with high selectivity over N2 under ambient conditions. We believe SXU-121's development opens new avenues for creating a class of stable and low cost metal-triazine frameworks with potential diverse functionalities.

Protonated covalent organic frameworks for green and effective recovery of Au(I) from thiosulfate solutions: Performance, DFT calculations, and mechanism insights

The recovery of Au(I) from thiosulfate leaching systems is important to ensure the sustainable use of strategic metal resources. In this study, two ionic covalent-organic frameworks (iCOFs), Tmp-Tpa COF-Cl and Tmp-Tpa COF-SO4, were synthesized through a post-modification strategy guided by theoretical calculations. Acid modification redistributed the surface charge of Tmp-Tpa COF due to the protonation of nitrogen atoms, which enabled the efficient and selective recovery of Au(I) from a thiosulfate solution. The Au(I) adsorption capacities of Tmp-Tpa COF-Cl and Tmp-Tpa COF-SO4 were 69.8 mg/g and 71.3 mg/g, respectively, which were significantly higher than those of previously reported materials. Adsorption equilibrium isotherms and kinetic studies revealed that the adsorption of Au(I) onto iCOFs conformed to the Langmuir and quasi-second-order kinetics model, showing that Au(I) underwent uniform monolayer chemisorption on the surface of the iCOFs. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared (FTIR) spectroscopy and density functional theory (DFT) calculations indicated that the adsorption of Au(I) onto Tmp-Tpa COF-Cl and Tmp-Tpa COF-SO4 was mainly because acid modification converted –C = N to –C = NH+-, which enhanced the strength of electrostatic attraction and coordination with Au(S2O3)23− complexes. Acidic thiourea rapidly eluted Au(I) adsorbed onto the iCOFs and simultaneously regenerated Tmp-Tpa COF-Cl. Even during the fifth adsorption/desorption cycle, the adsorption and desorption efficiencies of the iCOF still reached 86.6 % and 97.7 %, respectively. In addition, Tmp-Tpa COF prepared by Knoevenagel condensation was inexpensive (less than $50/kg) and did not require the use of organic solvents, enabling large-scale green production. This work provides an innovative method for the efficient, selective, and high-capacity recovery of gold from thiosulfate leachate.

Powder X-ray diffraction of nintedanib esylate hemihydrate, (C31H33N5O4)(C2H5O3S)(H2O)0.5

The crystal structure of nintedanib esylate hemihydrate was refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Nintedanib esylate hemihydrate crystallizes in space group P-1 (#2) with a = 11.5137(1), b = 16.3208(4), c = 19.1780(5) Å, α = 69.0259(12), β = 84.4955(8), γ = 89.8319(6)°, V = 3347.57(3) Å3, and Z = 4 at 295 K. Hydrogen bonds are prominent in the crystal structure. The water molecule forms two medium-strength O–H⋯O hydrogen bonds to one of the esylate anions. The protonated nitrogen atom in each cation forms a N–H⋯O hydrogen bond to an esylate anion. The ring N–H groups form strong intramolecular N–H⋯O hydrogen bonds to carbonyl groups. The ring N–H groups form intramolecular N–H⋯O hydrogen bonds to esylate anions. Many C–H⋅⋅⋅O hydrogen bonds (and one C–H⋯N hydrogen bond), with aromatic C–H, methylene groups and methyl groups as donors, are present. The hydrogen bonding patterns of the two cations differ considerably. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®)

An unexpected tautomer: synthesis and crystal structure of N-[6-amino-4-(methylsulfanyl)-1,2-dihydro-1,3,5-triazin-2-ylidene]benzenesulfonamide

The title compound, C10H11N5O2S2, consists of an unexpected tautomer with a protonated nitrogen atom in the triazine ring and a formal exocyclic double bond C=N to the sulfonamide moiety. The ring angles at the unsubstituted nitrogen atoms are narrow, at 115.57 (12) and 115.19 (12)°, respectively, whereas the angle at the carbon atom between these N atoms is very wide, 127.97 (13)°. The interplanar angle between the two rings is 79.56 (5)°. The molecules are linked by three classical hydrogen bonds, forming a ribbon structure. There are also unusual linkages involving three short contacts (< 3 Å) from a sulfonamide oxygen atom to the C—NH—C part of a triazine ring.

Efficient removal of uranium under strong acid based on charge separation and protonation coupled covalent organic frameworks

Efficient removal of UO22+ from radioactive wastewater under strong acid conditions remains a significant challenge due to the competition of excess H+ for adsorption and reduction sites. Here, covalent organic framework with complete charge separation and protonation properties (DANT-BTT) was synthesized for efficient removal of UO22+ under strong acids. The DANT-BTT with strong electron-deficient naphthalimide significantly extended light absorption and enhanced intramolecular charge transfer, which significantly improve the separation efficiency of electrons and holes. Additionally, the auxiliary coordination of hydroxyl groups after protonation provides unparalleled selectivity for UO22+ in strong acids, effectively preventing the competition of H+ for adsorption sites. Protonation of nitrogen atoms and ketones also extends light absorption and store electrons, further enhancing the photocatalytic performance of DANT-BTT. Consequently, DANT-BTT can achieve 71 % photoreduction UO22+ efficiency (pH 1) after 60 min irradiation, where dark adsorption accounts for 43 %. This work provides a strategy for the efficient reduction of U(VI) under strong acids.

Effect of Protonation on the Spectral–Luminescent and Photochemical Properties of a Bis(styrylbenzoquinoline) Dyad with the Naphthylene Framework and of Corresponding Dibenzoquinolylcyclobutane

The photophysical and photochemical properties of the protonated forms of both covalently bound biphotochromic dyad D44N containing two styrylbenzo[f]quinoline (SBQ) photochromes and corresponding cyclobutane CB44N containing two benzo[f]quinoline (BQ) substituents have been studied. CB44N is formed from D44N as a result of a reversible [2+2] photocycloaddition (PCA) reaction. The dyad and cyclobutane contain the 3-hydroxy-2-naphthoic acid (NA) moiety as a bridging group. It has been shown that the protonation of nitrogen atoms in the SBQ and BQ groups leads to bathochromic shifts in the absorption spectra and bathofloral shifts in the fluorescence spectra of the dyad and cyclobutane. In the protonated dyad, the quantum yield of the PCA reaction decreases, presumably due to the Coulomb repulsion, which prevents the cations of the protonated SBQ photochromes from approaching each other. In protonated cyclobutane, the quantum yield of the reverse four-membered ring opening reaction (retro-PCA), on the contrary, increases due to the absence of a competitive process of energy transfer from BQ to NA, which was previously observed in neutral cyclobutane

ACID-BASE PROPERTIES OF ALKYLENE­DIAMINETETRA (METHYLENEPHOSPHONIC) ACIDS

The acid-base characteristics of ethylenediaminetetra(methylenephosphonic) (edtmp), tetramethylenediaminetetra(methylenephosphonic) (tetdtmp) and pentamethylenediaminetetra(methylenephosphonic) (pendtmp) acids were investigated by means of pH-potentiometry and 31P NMR spectroscopy. Calculated and estimated values of acid dissociation constants (pK) for edtmp (рК1<2, рК2<2, рК3=3.07, рК4=5.17, рК5=6.52, рК6=7.97, рК7=9.65, рК8=10.94), for tetdtmp (рК1<2, рК2=4.48, рК3=5.34, рК4=6.13, рК5=6.66, рК6=10.08, рК7~11.4, рК8~11.5) and for pendtmp (рК1<2, рК2=4.22, рК3=5.56, рК4=6.16, рК5=7.66, рК6=10.99, рК7~11.5, рК8~11.6) were obtained. The values of the acid dissociation constants indicate a decrease in the acidity of phosphonic groups and an increase in the basicity of amino groups with increasing hydrocarbon chain length between the two nitrogen atoms in the edtmp, tetdtmp, and pendtmpseries. Based on the values of the calculated constants for the formation of anions of tetra­phosphonic acids, diagrams of the distribution of their equilibrium concentrations depending on pH were constructed, which indicate the state of acid-base equilibrium, the charge and the ratio of concentrations between anions with different degrees of protonation at certain pH values.
 According to the data of 31P NMR spectro­scopy, the formation of intramolecular hydrogen bonds between the deprotonated oxygen atoms of one amino(methylphosphonic) group with protonated nitrogen atom of another amino(methylphosphonic) group was established in the case of edtmp. In the case of pendtmp and tetdtmp, the formation of intermolecular hydrogen bonds between distant amino(me­thyl­phosphonic) groups is impossible due to the presence of steric hindrances.

Revealing the structure and mechanisms of action of a synthetic opioid with model biological membranes at the air-water interface

Synthetic opioids such as piperazine derivative called MT-45 interact with opioid receptors in a manner similar to morphine leading to euphoria, a sense of relaxation and pain relief and are commonly used as substituents of natural opioids. In this study we show the changes in the surface properties of nasal mucosa and intestinal epithelial model cell membranes formed at the air – water interface using Langmuir technique upon the exposure to MT-45. Both membranes constitute the first barrier to absorb this substance into the human body. The presence of the piperazine derivative affects the organization of both DPPC and ternary DMPC:DMPE:DMPS monolayers treated as simple models of nasal mucosa and intestinal cell membranes, respectively. This novel psychoactive substance (NPS) leads to the fluidization of the model layers, which may indicate their increased permeability. MT-45 has a greater influence on the ternary monolayers characteristic of the intestinal epithelial cells than nasal mucosa. It might be attributed to the increased attractive interactions between the components of the ternary layer, which in turn increase the interactions with a synthetic opioid. Additionally, the crystal structures of MT-45 determined by single-crystal and powder X-ray diffraction methods allowed us to both provide useful data for facilitating the identification of synthetic opioids as well as to attribute the effect of MT-45 to the ionic interactions between protonated nitrogen atoms and negatively charged parts of the polar heads of the lipids.

A multifunctional fluorescence MOF material: Triple-channel pH detection for strong acid and strong base, recognition of moxifloxacin and tannic acid

A luminescent 1D metal–organic framework [Co(apba)2(H2O)2] (1) was solvothermal synthesized by using 4-(2-aminopyrimidine-5-yl)benzoic acid (Hapba) as ligand. 1 showed pronounced sensing properties with triple-channel specific recognition ability for strong acid-base and weak acid. From pH = 3.5 to 2.0, the fluorescence quenching percentage reached 1064 % per pH at 412 nm due to the protonation of –NH2. In the pH region of 3.5–4.5, 1 realizes wavelength-based pH detection depending on the wavelength shift of 30 nm from 412 nm to 382 nm originating from the protonation of nitrogen atom in pyrimidine. In the pH range of 11.5–13.4, the fluorescence quenching percentage reached 2099 % per pH relying on the interaction between OH– and uncoordinated oxygen atom on carboxylate group. This is the first example that a MOF-based pH sensor can detect strong acid-base and weak acid, and their sensitivity to pH is likewise the highest among all pH fluorescent sensors. 1 can also detect antibiotic moxifloxacin (MOX) and polyphenol compound tannic acid (TA) with the limit of detection (LOD) at the 10 ppb level. In the recognition of 1 for MOX, KSV is 2.05 × 105 M−1 (0–100 μM) and LOD reaches 43 nM, which is the first case of a MOF-based MOX sensor so far. The fluorescence response of 1 to TA is also apparent with the KSV value of 7.55 × 105 M−1 (0–0.05 μM) and LOD of 11 nM. This is as well the only instance of MOF material sensing TA to date. Moreover, 1 can continuously track MOX and TA for up to 90 days. The sensing mechanisms of pH, MOX, and TA are also discussed in detail.

Octahedrons of 1,10-phenanthroline and 4′‑chloro-2,2′:6′,2″-terpyridine induced by protonation of nitrogen atoms: Synthesis and analysis

Two new octahedral compounds, [(phenH)(phen)]PF6 (phen = 1,10-phenanthroline) and [(ClterpyH2)(Clterpy)(H2O)](PF6)2 (Clterpy = 4′‑chloro-2,2′:6′,2″-terpyridine) were synthesized. Their light emission properties were investigated by experimental measurements and theoretical calculations, and the relationship between the emission and structure of the protonated compounds was studied. Time-dependent density functional theory calculations revealed that [(phenH)(phen)]PF6 and [(ClterpyH2)(Clterpy)(H2O)](PF6)2 exhibit hydrogen-bonded octahedrons, even in the excited states. In [(phenH)(phen)]PF6, an octahedron was formed by three hydrogen bonds and the dihedral angle between phenH+ and phen was 78° In [(ClterpyH2)(Clterpy)(H2O)](PF6)2, four hydrogen bonds were detected forming an octahedron with the angle between ClterpyH22+ and Clterpy being nearly 90° [(ClterpyH2)(Clterpy)(H2O)](PF6)2 also exhibited a unique configuration attributed to the attachment of a proton to the nitrogen, which causes an intense emission (Φ = 0.290). NMR analyses revealed that the presence of phenH+, phen, ClterpyH22+, and Clterpy did not present any additional peaks to the spectra, indicating that the H signals were averaged.

Interplay between the Enamine and Imine Forms of the Hydrolyzed Imipenem in the Active Sites of Metallo-β-lactamases and in Water Solution.

Deactivation of the β-lactam antibiotics in the active sites of the β-lactamases is among the main mechanisms of bacterial antibiotic resistance. As drugs of last resort, carbapenems are efficiently hydrolyzed by metallo-β-lactamases, presenting a serious threat to human health. Our study reveals mechanistic aspects of the imipenem hydrolysis by bizinc metallo-β-lactamases, NDM-1 and L1, belonging to the B1 and the B3 subclasses, respectively. The results of QM(PBE0-D3/6-31G**)/MM simulations show that the enamine product with the protonated nitrogen atom is formed as the major product in NDM-1 and as the only product in the L1 active site. In NDM-1, there is also another reaction pathway that leads to the formation of the (S)-enantiomer of the imine form of the hydrolyzed imipenem; this process occurs with the higher energy barriers. The absence of the second pathway in L1 is due to the different amino acid composition of the active site loop. In L1, the hydrophobic Pro226 residue is located above the pyrroline ring of imipenem that blocks protonation of the carbon atom. Electron density analysis is performed at the stationary points to compare reaction pathways in L1 and NDM-1. Tautomerization from the enamine to the imine form likely happens in solution after the dissociation of the hydrolyzed imipenem from the active site of the enzyme. Classical molecular dynamics simulations of the hydrolyzed imipenem in solution, both with the neutral enamine and the negatively charged N-C2-C3 fragment, demonstrate a huge diversity of conformations. The vast majority of conformations blocks the C3-atom from the side required for the (S)-imine formation upon tautomerization. Thus, according to our calculations, formation of the (R)-imine is more likely. QM(PBE0-D3/6-31G**)/MM molecular dynamics simulations of the hydrolyzed imipenem with the negatively charged N-C2-C3 fragment followed by the Laplacian bond order analysis demonstrate that the N═C2-C3- resonance structure is the most pronounced that facilitates formation of the imine form. The proposed mechanism of the enzymatic enamine formation and its subsequent tautomerization to the imine form in solution is in agreement with the recent spectroscopic and NMR studies.

New N-aryl-N′-aryl-/(thio)ureido-/sulfamoylamino-derivatives of alkyl/alkylcarbamoyl piperazines: Effect of structural modifications on selectivity over 5-HT1A receptor

The 5-HT1A receptors are an important biological target in the treatment of CNS diseases. Recently, their importance in the context of non-CNS disease entities has also been postulated. In the light of these reports, we designed a new group of urea derivatives of N-aryl-N′-aryl-/(thio)ureido-/sulfamoylamino-derivatives of alkyl/alkylcarbamoyl piperazines as 5-HT1AR ligands, focusing on increasing receptor selectivity. We made structural modifications in three areas of the molecule. In the course of our research, we obtained a ligand with reduced basicity (6f), which, despite the loss of the protonable nitrogen atom, did not lose its affinity for the 5-HT1AR (Ki = 35 nM) with a simultaneous increase in selectivity. In particular, a decrease in affinity for D2R (Ki = 1940 nM) was observed, which was analyzed using molecular modeling methods, including FMO and molecular dynamics. Basic ADME-Tox parameters were characterized for 6f, confirming its potential applicability in pharmacotherapy.

Epigenetic Modifications and Neurodegenerative Disorders: A Biochemical Perspective.

Methylations in living cells are methyl groups attached to amino acids, DNA, RNA, and so on. However, their biochemical roles have not been fully defined. A theory has been postulated that methylation leads to hyperconjugation, and the electron-donating feature weakens a nearby chemical bond, which increases the bond length of C4-N4 of 5-methylcytosine, therefore weakening the C4-N4 bond and resulting in stronger protonation or hydrogen bonding of the N4 nitrogen atom. Protonation can give rise to the generation of mutagenic and carcinogenic strong acids such as HCl, which are also capable of solubilizing stressful, insoluble, and stiff salts. Insoluble and rigid salts such as calcium oxalate and/or calcium phosphate were recently proposed as a primary cause of some neurodegenerative disorders. Protonation of nitrogen atoms in 5-methylcytosine enhances the interaction with negatively charged phosphate groups and contributes to the formation of compact heterochromatin. The electronegativity of the oxygen atoms in the modifications of 5-hydroxymethylcytosine or 5-formylcytosine can shorten the lengths of adjacent bonds with no increase of cation affinity in N4. The carboxyl group in 5-carboxylcytosine is a weak acid capable of antagonizing mutagenic HCl and modestly helping solubilize insoluble salts. Electron delocalization of the methyl group in N4-methylcytosine results in a lower affinity of N4 to cations. The positive charge at N3 in the resonance structure of 3-methylcytosine is lessened by the electron-donating attribute of the methyl group attached to the N3 atom, consequently reducing acid formation. The electron delocalization of three methyl groups decreases the positive charge in the amino nitrogen in the side group of lysine 4 in histone H3, weakening interactions with phosphate groups and consequently activating gene expression. The carbonyl oxygen in 8-oxo-7,8-dihydroguanine draws protons and accumulates HCl, accounting for its moderate mutation propensity and potential capacity to solubilize stiff salts. The biochemical insight will further our understanding on the crosstalk of genetics and epigenetics in the etiology of neurodegenerative diseases.

Dual-Functional Metal-Organic Framework for Luminescent Detection of Carcinoid Biomarkers and High Proton Conduction.

It remains a challenge to exploit dual-functional metal-organic frameworks (MOFs) for applications, including luminescence detection and proton conduction. With the deliberate selection of the bifunctional organic ligand 5-sulfoisophthalic acid monosodium salt (NaH2bts), and the phosphonic acid ligand N,N'-piperazine (bismethylenephosphonic acid; H4L), a robust three-dimensional (3D) noninterpenetrating dual-functional MOF, [Tb(H2L)(H2bts)(H2O)]·H2O (1), has been synthesized hydrothermally. On the basis of the excellent thermal and chemical as well as superior luminescence stabilities in water and solutions with different pHs, 1 can serve as the simple, rapid, and highly selective and sensitive luminescence detection of the carcinoid biomarkers 5-hydroxytryptamine (HT) and its metabolite 5-hydroxyindole-3-acetic acid (HIAA) with detection limits of nanomolar magnitude in water and in simulated blood plasma and urine systems. Due to the change in the signals that could be readily differentiated by the naked eye under a UV lamp, a portable test paper has been developed. The probable quenching mechanisms are discussed in detail. In addition, a great number of hydrogen-bonding networks are formed among the uncoordinated carboxylic oxygen atoms, sulfonate oxygen atoms, protonated nitrogen atoms, and water molecules, which provide potential proton-hopping sites for proton conduction, leading to a maximum proton conductivity of 2.3 × 10-4 S cm-1 at 368 K and 95% relative humidity. The above results suggest that rationally designed dual-functional MOFs can open an avenue for the development of occupational diagnostic tools and alternative energy technology.

Crystal structure of palbociclib isethionate Form B, (C24H30N7O2)(C2H5O4S)

The crystal structure of palbociclib isethionate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Palbociclib isethionate crystallizes in space group P-1 (#2) with a = 8.71334(4), b = 9.32119(6), c = 17.73725(18) Å, α = 80.0260(5), β = 82.3579(3), γ = 76.1561(1)°, V = 1371.282(4) Å3, and Z = 2. The crystal structure is dominated by cation⋯anion and cation⋯cation hydrogen bonds, which result in layers roughly parallel to the (104) plane. Both hydrogen atoms on the protonated nitrogen atom of the pyrimidine ring participate in strong hydrogen bonds to the anions. One proton binds to the sulfonate group, while the other bonds to the hydroxyl group of the isethionate anion. The hydroxyl group of the anion acts as a donor to a ketone oxygen atom in the cation. There are also strong N–H⋯N hydrogen bonds, which occur in pairs linking the cations into dimers with rings having a graph set R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.

Crystal structure of levocetirizine dihydrochloride Form I, C21H27ClN2O3Cl2

The crystal structure of levocetirizine dihydrochloride Form I has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Levocetirizine dihydrochloride Form I apparently crystallizes in space group P21/n (#14) with a = 24.1318(21), b = 7.07606(9), c = 13.5205(7) Å, β = 97.9803(4)°, V = 2286.38(12) Å3, and Z = 4. The crystal structure consists of interleaved double columns of cations and anions along the short b-axis. The hydrogen bonds link the cations and anions along this axis. Each protonated nitrogen atom forms a strong N–H⋯Cl hydrogen bond to one of the chloride anions. The carboxylic acid group also forms an H-bond to Cl56, resulting in a ring with a graph set R1,2(10). The centrosymmetric P21/n model for the crystal structure of levocetirizine dihydrochloride is better than the non-centrosymmetric P21 model, even though levocetirizine is a chiral molecule; the sample exhibits weak second-harmonic generation, and three weak peaks which violate the glide plane are observed. The centrosymmetric model is better by statistical, graphical, and energetic measures, as well as by chemical reasonableness. To accommodate the chiral molecule in a centrosymmetric space group, the chiral central carbon atom was disordered over two half-occupied positions, so that each cation site could be occupied by a cation of the correct chirality. A powder pattern from a Le Bail extraction of this synchrotron data set is included in the Powder Diffraction File™ as entry 00-066-1627.

Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O)(H2C6H5O7)

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P212121 (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) Å, V = 2326.411(6) Å3, and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation⋯anion and anion⋯anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Crystal structure of tamsulosin hydrochloride, C20H29N2O5SCl

The crystal structure of tamsulosin hydrochloride has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Tamsulosin hydrochloride crystallizes in space groupP21(#4) witha= 7.62988(2),b= 9.27652(2),c= 31.84996(12) Å,β= 93.2221(2)°,V= 2250.734(7) Å3, andZ= 4. In the crystal structure, two arene rings are connected by a carbon chain oriented roughly parallel to thec-axis. The crystal structure is characterized by two slabs of tamsulosin hydrochloride molecules perpendicular to thec-axis. As expected, each of the hydrogens on the protonated nitrogen atoms makes a strong hydrogen bond to one of the chloride anions. The result is to link the cations and anions into columns along theb-axis. One hydrogen atom of each sulfonamide group also makes a hydrogen bond to a chloride anion. The other hydrogen atom of each sulfonamide group forms bifurcated hydrogen bonds to two ether oxygen atoms. The powder pattern is included in the Powder Diffraction File™ as entry 00-065-1415.

Crystal structure of edoxaban tosylate monohydrate Form I, (C24H31ClN7O4S)(C7H7O3S)(H2O)

The crystal structure of edoxaban tosylate monohydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Edoxaban tosylate monohydrate crystallizes in space group P21 (#4) with a = 7.55097(2), b = 7.09010(2), c = 32.80420(21) Å, β = 96.6720(3)°, V = 1744.348(6) Å3, and Z = 2. The crystal structure consists of alternating layers of edoxaban cations and tosylate anions along the c-axis. The water molecules lie near the sulfonate end of the tosylate anions. The solid-state conformation of the edoxaban cation is determined by intermolecular interactions. The protonated nitrogen atom forms a strong N–H⋯O hydrogen bond to one of the tosylate oxygens. Only one of the water molecule hydrogens acts as a donor in an O–H⋯O hydrogen bond. The tosylate oxygens act as acceptors in a number of C–H⋯O hydrogen bonds. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™.

Crystal structure of (E)-doxepin hydrochloride, C19H22NOCl

The crystal structure of (E)-doxepin hydrochloride has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. (E)-doxepin hydrochloride crystallizes in space group P21/a (#14) with a = 13.78488(7), b = 8.96141(7), c = 14.30886(9) Å, β = 96.5409(5)°, V = 1756.097(12) Å3, and Z = 4. There is a strong discrete hydrogen bond between the protonated nitrogen atom and the chloride anion. There are six C–H⋯Cl hydrogen bonds between the methyl groups and the chloride, as well as additional hydrogen bonds from methylene groups and the vinyl proton. The hydrogen bonds are important in determining the solid-state conformation of the cation. The compound is essentially isostructural to amitriptyline hydrochloride. The powder pattern is included in the Powder Diffraction File™ as entry 00-066-1613.