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Eight new amorphous organic salts of folic acid (FA) were prepared by mechanochemistry. FA can prevent cardiovascular and neurological diseases. Mechanochemistry overcomes serious FA solubility issues avoiding the use of toxic solvents. Due to low FA solubility, therapeutic effects in supplements and drugs are not achieved. Current strategies to improve FA solubility include its derivatization by using complex synthetic procedures. Herein, a simple and green procedure, avoiding structural modifications, was designed using mechanochemistry. Biocompatible amine‐derivative coformers were strategically combined with FA to obtain salts with good physicochemical properties. New 1 : 1 and 1 : 2 amorphous FA salts offer 10 to 10,000 times better aqueous solubility and 10 to 100 times better octanol‐water partition coefficient values (Koctanol/water) than FA alone. Koctanol/water is considered as a surrogate of cell permeability. No toxic effects in normal human primary dermal fibroblasts were detected for the prepared FA salts. Our findings suggest that 1 : 2 FA salts of choline hydroxide and derivatives could be good candidates for future pharmaceutical/nutraceutical applications. [ABSTRACT FROM AUTHOR]

Indazole is known as an important structural motif in medicinal chemistry and, recently, has also gained attention in other areas, such as materials chemistry, with many studies showing different potential applications for their regioisomers. Phosphonates are also a class of compounds with diverse applications, ranging from medicinal to material applications. Here we present the synthesis of 1H‐ and 2H‐indazolephosphonic acid derivatives substituted at C‐3, involving mono‐ or bisphosphonic acids, from their corresponding carboxylic acid and esters. These compounds were fully characterized, and their spectroscopic data were evaluated to identify and distinguish the structural scaffold of each phosphonic acid. Crystallization of [hydroxy(1‐methyl‐1H‐indazol‐3‐yl)methanediyl]bis(phosphonic acid) 7 afforded crystals suitable for single crystal X‐ray diffraction studies and its crystal structure details are also discussed. [ABSTRACT FROM AUTHOR]

Hydrogen bonds (HBs) play a key role in the supramolecular arrangement of crystalline solids and, although they have been extensively studied, the influence of their strength and geometry on crystal packing remains poorly understood. Here we describe the crystal structures of two novel protic gabapentin (GBP) pharmaceutical salts prepared with the coformers methanesulfonic acid (GBP:METHA) and ethanesulfonic acid (GBP:ETHA). This study encompasses experimental and computational electronic structure analyses of 1H NMR chemical shifts (CSs), upon in silico HB cleavage. GBP:METHA and GBP:ETHA crystal packing comprise two main structural domains: an ionic layer (characterized by the presence of charge‐assisted +NHGBP⋯O−METHA/ETHA HB interactions) and a neutral layer generated in a different way for each salt, mainly due to the presence of bifurcated HB interactions. A comprehensive study of HB networks is presented for GBP:METHA, by isolating molecular fragments involved in distinct HB types (NH⋯O, OH⋯O, and CH⋯O) obtained from in silico disassembling of an optimized three‐dimensional packing structure. Formation of HB leads to calculated 1H NMR CS changes from 0.4 to ~5.8 ppm. This study further attempts to assess how 1H NMR CS of protons engaged in certain HB are affected when other nearby HB, involving bifurcated or geminal/vicinal hydrogen atoms, are removed. [ABSTRACT FROM AUTHOR]

Abstract: The preparation and characterization of a whole family of hydrated ionic co‐crystals formed by both enantiopure l‐proline and racemic dl‐proline with LiX (X=Cl, Br, I) are reported. The chiral preference of the lithium cation for homochiral coordination, both in the formation of crystalline conglomerates (with Cl and Br) and racemates (with Cl and I), in which molecules of opposite chirality are confined to distinct crystal layers, is discussed. Dehydration processes for all hydrated crystals have also been investigated. [ABSTRACT FROM AUTHOR]

An alternative, efficient, and green synthetic strategy for the preparation of pharmaceutical ionic liquids using mechanochemistry (MechanoAPI-ILs) is reported. Six new API-ILs based on gabapentin and l-glutamic acid were successfully synthesized and characterized, demonstrating that mechanochemistry is a very promising synthetic strategy. Results compare both the new and the classical approach and clearly show the advantages of the new method. This new technique is faster, solvent free, reproducible, selective, and leads to higher yields. [ABSTRACT FROM AUTHOR]

ABSTRACT Novel tetraethyl ethylene-1,1-bisphosphonate esters derived from 1 H-indazole, 1 H-pyrazolo[3,4- b]pyridine, and 1 H-pyrazolo[3,4- b]quinoline were synthesized by a Michael addition reaction of tetraethyl ethylidene-1,1-bisphosphonate with the corresponding heterocycle, using conventional heating and microwave-assisted methods. The microwave-assisted method provides shorter reaction times and better yields. The hydrolysis of bisphosphonates afforded the corresponding bisphosphonic acids or salt, using concentrated hydrochloric acid or TMSBr/collidine, respectively. All new compounds were fully characterized, and their structures were assigned using 1H, 31P, and 13C NMR and IR spectroscopies and mass spectrometry. The molecular structure of compound 6 was confirmed by X-ray diffraction studies. [ABSTRACT FROM AUTHOR]

New bis- and tris(iminopyrrole)-functionalized linear (1,2-(HNC4H3-C(H)N)2-C6H4 ( 2), 1,3-(HNC4H3-C(H)N)2-C6H4 ( 3), 1,4-(HNC4H3-C(H)N)2-C6H4 ( 4), 4,4′-(HNC4H3-C(H)N)2-(C6H4-C6H4) ( 5), 1,5-(HNC4H3C-(H)N)2-C10H6 ( 6), 2,6-(HNC4H3C-(H)N)2-C10H6 ( 7), 2,6-(HNC4H3C-(H)N)2-C14H8 ( 8)) and star-shaped (1,3,5-(HNC4H3-C(H)N-1,4-C6H4)3-C6H3 ( 9)) π-conjugated molecules were synthesized by the condensation reactions of 2-formylpyrrole ( 1) with several aromatic di- and triamines. The corresponding linear diboron chelate complexes (Ph2B[1,3-bis(iminopyrrolyl)-phenyl]BPh2 ( 10), Ph2B[1,4-bis(iminopyrrolyl)-phenyl]BPh2 ( 11), Ph2B[4,4′-bis(iminopyrrolyl)-biphenyl]BPh2 ( 12), Ph2B[1,5-bis(iminopyrrolyl)-naphthyl]BPh2 ( 13), Ph2B[2,6-bis(iminopyrrolyl)-naphthyl]BPh2 ( 14), Ph2B[2,6-bis(iminopyrrolyl)-anthracenyl]BPh2 ( 15)) and the star-shaped triboron complex ([4′,4′′,4′′′-tris(iminopyrrolyl)-1,3,5-triphenylbenzene](BPh2)3 ( 16)) were obtained in moderate to good yields, by the treatment of 3- 9 with B(C6H5)3. The ligand precursors are non-emissive, whereas most of their boron complexes are highly fluorescent; their emission color depends on the π-conjugation length. The photophysical properties of the luminescent polyboron compounds were measured, showing good solution fluorescence quantum yields ranging from 0.15 to 0.69. DFT and time-dependent DFT calculations confirmed that molecules 10 and 16 are blue emitters, because only one of the iminopyrrolyl groups becomes planar in the singlet excited state, whereas the second (and third) keeps the same geometry. Compound 13, in which planarity is not achieved in any of the groups, is poorly emissive. In the other examples ( 11, 12, 14, and 15), the LUMO is stabilized, narrowing the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital (HOMO-LUMO), and the two iminopyrrolyl groups become planar, extending the size of the π-system, to afford green to yellow emissions. Organic light-emitting diodes (OLEDs) were fabricated by using the new polyboron complexes and their luminance was found to be in the order of 2400 cd m−2, for single layer devices, increasing to 4400 cd m−2 when a hole-transporting layer is used. [ABSTRACT FROM AUTHOR]

Reactions of 2-( N-arylimino)pyrroles (HNC4H3C(H)N-Ar) with triphenylboron (BPh3) in boiling toluene afford the respective highly emissive N, N′-boron chelate complexes, [BPh2{κ2 N, N′-NC4H3C(H)N-Ar}] (Ar=C6H5 ( 12), 2,6-Me2-C6H3 ( 13), 2,6- iPr2-C6H3 ( 14), 4-OMe-C6H4 ( 15), 3,4-Me2-C6H3 ( 16), 4-F-C6H4 ( 17), 4-NO2-C6H4 ( 18), 4-CN-C6H4 ( 19), 3,4,5-F3-C6H2 ( 20), and C6F5 ( 21)) in moderate to high yields. The photophysical properties of these new boron complexes largely depend on the substituents present on the aryl rings of their N-arylimino moieties. The complexes bearing electron-withdrawing aniline substituents 17- 20 show more intense (e.g., ϕf=0.71 for Ar=4-CN-C6H4 ( 19) in THF), higher-energy (blue) fluorescent emission compared to those bearing electron-donating substituents, for which the emission is redshifted at the expense of lower quantum yields ( ϕf=0.13 and 0.14 for Ar=4-OMe-C6H4 ( 15) and 3,4-Me2-C6H3 ( 16), respectively, in THF). The presence of substituents bulkier than a hydrogen atom at the 2,6-positions of the aryl groups strongly restricts rotation of this moiety towards coplanarity with the iminopyrrolyl ligand framework, inducing a shift in the emission to the violet region ( λmax=410-465 nm) and a significant decrease in quantum yield ( ϕf=0.005, 0.023, and 0.20 for Ar=2,6-Me2-C6H3 ( 13), 2,6- iPr2-C6H3 ( 14), and C6F5 ( 21), respectively, in THF), even when electron-withdrawing groups are also present. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have indicated that the excited singlet state has a planar aryliminopyrrolyl ligand, except when prevented by steric hindrance ( ortho substituents). Calculated absorption maxima reproduce the experimental values, but the error is higher for the emission wavelengths. Organic light-emitting diodes (OLEDs) have been fabricated with the new boron complexes, with luminances of the order of 3000 cd m−2 being achieved for a green-emitting device. [ABSTRACT FROM AUTHOR]

We present here the NHC-dirhodium(II)/DBU-catalyzed ring expansion reaction of isatins with ethyl diazoacetate. This new one-pot protocol yields the ethyl 3-hydroxy-2(1 H)-oxoquinoline-4-carboxylate core, regioselectively and in good to excellent yields. A DFT mechanistic study indicates metallocarbene formation between the 3-hydroxyindole-diazo intermediate and the dirhodium(II) complex to be the rate-limiting step of the reaction. The synthesized ethyl 3-hydroxy-2(1 H)-oxoquinoline-4-carboxylate core could be readily converted to viridicatin alkaloids, in yields up to 80 % by a microwave-assisted Suzuki-Miyaura cross coupling of the 3-hydroxy-4-bromoquinolin-2(1 H)-one with arylboronic acid. [ABSTRACT FROM AUTHOR]

A series of new cationic and neutral (Ar-BIAN)copper(I) complexes [in which Ar-BIAN = bis(aryl)acenaphthenequinonediimine] was synthesised and characterised by elemental analysis, 1D and 2D NMR spectroscopy and single-crystal X-ray diffraction. The cationic complexes of the general formula [Cu(Ar-BIAN) L2]BF4 [ L2 = (PPh3)2 ( 1), dppe ( 2), dppf ( 3), (AsPh3)2 ( 4); Ar = 4- iPrC6H4 ( a), 4-MeOC6H4 ( b), 4-NO2C6H4 ( c), 2- iPrC6H4 ( d), Ph2PCH2CH2PPh2 (dppe), (Ph2PC5H4)2Fe (dppf)] were synthesised by reaction of [Cu(EPh3)4]BF4 (E = P or As) and equimolar amounts of Ar-BIAN ligands, or by reaction of equimolar amounts of [Cu(NCMe)4]BF4, 4- iPrC6H4-BIAN ( a) and diphosphanes dppe or dppf, in dichloromethane, whereas the neutral complexes of the types [CuX(Ar-BIAN)(EPh3)] [X = Cl, E = P ( 5); X = I, E = P ( 6); X = Cl, E = As ( 9)] and [{CuX(Ar-BIAN)}2] [X = Cl ( 7), I ( 8); Ar = a, b, c, d, 2,4,6-Me3C6H2 ( e), 2,6- iPr2C6H3 ( f)] were prepared by reaction of CuCl or CuI with equimolar amounts of Ar-BIAN and EPh3 (E = P, As or Sb) in acetonitrile under reflux conditions. The type of ancillary ligand EPh3 and the aryl substituents on Ar-BIAN play crucial roles in determining the formation of cationic or neutral copper(I) complexes. No copper(I) complexes containing coordinated SbPh3 were isolated; all the corresponding attempts led to dimeric complexes 7 or 8. Most of the complexes crystallised easily. Their study by X-ray diffraction revealed distorted-tetrahedral geometries around the copper(I) centres, which are quite influenced by the various aryl substituents on Ar-BIAN and the ancillary ligands EPh3. All complexes 1- 9 except cationic dppf derivative 3a are active catalysts for cycloaddition reactions of alkynes and azides, and also show good tolerance towards functionalised substituents of alkynes and azides. Among them, the PPh3-coordinated complexes 1, 5 and 6 afforded the highest catalytic activities [turnover frequency = 26.9-45.7 h-1]. [ABSTRACT FROM AUTHOR]

The asymmetric dirhodium(II)-catalyzed intramolecular CH insertion of α-diazo acetamides in water is described for the first time. The use of natural α-amino acids as chiral ligands allowed the preparation of novel dirhodium(II) homochiral complexes by a simple procedure consisting of the in situ ligand exchange starting from dirhodium tetraacetate. The catalytic system was further reused up to 7 cycles and β-lactams were obtained in good yields and enantiomeric excess. [ABSTRACT FROM AUTHOR]

The article focuses on the crystal structures of 2-[(4-flourophenyl)iminomethyl]-pyrrole and 2-[(1H-pyrrol-2-ylmethylidene)-amino]benzonitrile. Pyrrole and its substituted derivatives are five-membered heterocyclic compounds that are used in the applications of anion-binding systems, bioactive molecules and pharmaceuticals. The structures consist of two independent molecules in a asymmetric unit that form dimers through N-H···N hydrogen bonds.

The article presents a paper about trans-Chlorido(phenyl)bis(triphenyl-phosphine)nickel(II) and its 1:1 cocrystal with chloridobis(triphenyl-phosphine)nickel(I). It mentions the interest attracted by a new class of neutral nickel catalysts based on salicylaldimine or anilinotropone ligands. A view of the crystal packing of cocrystal (3) along c, showing the alternating layers along a is provided.

The article discusses a study which compares and discusses the crystal structures and supramolecular arrangements of the metal-organic compound, tetra-μ-acetato-bis{[1,3-bis(2,6-diiso-propylphenyl)imidazol-2-ylidene]-rhodium(II)}(Rh-Rh) tetrahydro-furan tetrasolvate and toluene trisolvate. It cites that the molecular structures of the two complex molecules show a similar conformation, but due to the presence of various solvent molecules, the two solvates crystallize in different space groups and display quite diverse supramolecular assemblies.

The title compound, [1,2-bis(diphenylphosphino)ethane](η5-cyclo­penta­dienyl)(4-nitro­benzonitrile)iron(II) iodide, [Fe(η5-C5H5)(C7H4N2O2)(C26H4P2)]I, crystallizes in the non-centrosymmetric space group Cc, which is a promising result for obtaining quadratic non-linear optical properties. However, the packing shows that the iodide counter-ion promotes the cancellation of almost all the dipoles, resulting in a supra­molecular motif of cationic chains aligned in opposite directions making an angle of 35.2°. The use of PF6− as counter-ion induces the crystallization of the complex in a centrosymmetric space group. These results show that the introduction of different counter-ions, of different size and geometry, allows specific and directional inter­molecular inter­actions that can determine the formation of a particular type of crystal packing. [ABSTRACT FROM AUTHOR]

The structure of the title compound, [Ti(C2H6N)2(C6H8N)Cl], displays a η5 -coordination mode for the pyrrolyl ring, confirmed by the values of the slip parameter [0.073 (9) Å and the fold angle [4.6 (6)°]. This coordination is confirmed by NMR data, which point to the involvement of the complex in a fluxional process in solution above 285 K, passing through an intermediate involving simultaneously a metal-azaallyl and a metal-olefin bond. [ABSTRACT FROM AUTHOR]

In the title complex, trans-{2,2′-[cyclo­hexane-1,2-diyl­bis­(ni­t­rilo­methyl­idyne)]­di­phenol­ato-κ4 O, N, N′, O′}­nickel(II)-chloro­form (1/1), [Ni(C20H20N2O2)]·CHCl3, the Ni atom has a square-planar geometry, slightly tetrahedrally distorted. The Ni-N and Ni-O bonding distances are within the expected ranges for Ni-Schiff base derivatives. The di­imine bridge has a gauche conformation with the cyclo­hexyl ring almost coplanar with the NiN2O2 plane. The complex mol­ecules pack in dimers with an Ni⃛Ni distance of 3.59 (1) Å and form a three-dimensional structure displaying a herring-bone configuration. Channels are occupied by solvent mol­ecules, which are involved in C-H⃛O hydrogen bonds with the ligand O atoms. [ABSTRACT FROM AUTHOR]

A second polymorphic form (form II) of the previously reported 1,4,7-tris( p-tolylsulfonyl)-1,4,7-triazacyclononane (form I), C27H33N3O6S3, is presented. The molecular structures of the two forms display very different conformations, thus prompting the two forms to crystallize in two different space groups and exhibit quite diverse crystal structure assemblies. Form I crystallizes in the triclinic space group P , while form II crystallizes in the monoclinic space group P21/ n. The main differences between the two molecular structures are the conformations of the p-tosyl groups relative to each other and to the macrocyclic ring. The resulting crystal packing displays no classical hydrogen bonds, but different supramolecular synthons give rise to different packing motifs. [ABSTRACT FROM AUTHOR]

The title compound, (η5-cyclo­penta­dienyl)(4-nitro­benzo­nitrile-κ N)(trimethyl­phosphine-κ P)(triphenyl­phosphite-κ P)iron(II) hexa­fluoro­phosphate, [Fe(C5H5)(C7H4N2O2)(C18H15O3P)(C3H9P)]PF6, has been characterized by spectroscopic and X-ray diffraction in order to evaluate the tuning of the electron density at the metal centre and the extension of the π delocalization on the mol­ecule due to the presence of phosphite and phosphine co-ligands. The compound crystallizes in the centrosymmetric space group P21/ c, which destroys the possibility of exhibiting any quadratic non-linear optical properties. The packing shows a supramolecular zigzag chain of antiparallel cations connected via the PF6− anions through C—H⋯Fδ− inter­actions, with H⋯F distances ranging from 2.39 to 2.67 Å. Each zigzag chain is composed of isomeric organometallic fragments containing either R or S mol­ecules. These chains are connected through weak inter­molecular C—H⋯C inter­actions, forming a two-dimensional plane parallel to (101). [ABSTRACT FROM AUTHOR]

Two conformational polymorphs of trans-chlorido(phenyl)bis(triphenylphosphine)nickel(II), [Ni(C(6)H(5))Cl(C(18)H(15)P)(2)], (1), viz. orange needle-shaped crystals (form I) and brown prism-shaped crystals (form II), were obtained under different crystallization conditions from a mixture of toluene and n-hexane, and characterized by single-crystal X-ray diffraction at low temperature. These two forms were compared with that published previously [Zeller, Herdtweck & Strassner (2003). Eur. J. Inorg. Chem. pp. 1802-1806], characterized at room temperature. Additionally, blue-green prisms of a 1:1 cocrystal of complex (1) with chloridobis(triphenylphosphine)nickel(I), (2), viz. trans-chlorido(phenyl)bis(triphenylphosphine)nickel(II)-chloridobis(triphenylphosphine)nickel(I) (1/1), [Ni(C(6)H(5))Cl(C(18)H(15)P)(2)].[NiCl(C(18)H(15)P)(2)], (3), were obtained concomitantly with form I. In forms I and II, as well as in the cocrystal, the overall crystal packings are determined by an energetic interplay between intramolecular torsions and weak intermolecular C-H...pi and C-H...Cl interactions.

In the title compound, C10H11N, the molecules assemble as pseudo-dimers through pi-pi interactions, each dimer being rotated by about 90 degrees with respect to its neighbours. The relative positioning of the dimers and C-H...pi interactions give, when seen along a, a supramolecular zigzag arrangement. The compound contains a planar pyrroline ring and, as a whole, its molecular conformation is also planar, which represents the first example of a totally planar 2-substituted 1-pyrroline and the simplest ever reported by X-ray diffraction.

A second polymorphic form (form II) of the previously reported 1,4,7-tris(p-tolylsulfonyl)-1,4,7-triazacyclononane (form I), C(27)H(33)N(3)O(6)S(3), is presented. The molecular structures of the two forms display very different conformations, thus prompting the two forms to crystallize in two different space groups and exhibit quite diverse crystal structure assemblies. Form I crystallizes in the triclinic space group P\overline{1}, while form II crystallizes in the monoclinic space group P2(1)/n. The main differences between the two molecular structures are the conformations of the p-tosyl groups relative to each other and to the macrocyclic ring. The resulting crystal packing displays no classical hydrogen bonds, but different supramolecular synthons give rise to different packing motifs.

The title compound, [1,2-bis(diphenylphosphino)ethane](eta5-cyclopentadienyl)(4-nitrobenzonitrile)iron(II) iodide, [Fe(eta5-C5H5)(C7H4N2O2)(C26H4P2)]I, crystallizes in the non-centrosymmetric space group Cc, which is a promising result for obtaining quadratic non-linear optical properties. However, the packing shows that the iodide counter-ion promotes the cancellation of almost all the dipoles, resulting in a supramolecular motif of cationic chains aligned in opposite directions making an angle of 35.2 degrees. The use of PF6- as counter-ion induces the crystallization of the complex in a centrosymmetric space group. These results show that the introduction of different counter-ions, of different size and geometry, allows specific and directional intermolecular interactions that can determine the formation of a particular type of crystal packing.

The structure of the title compound, [Ti(C2H6N)2(C6H8N)Cl], displays a eta5-coordination mode for the pyrrolyl ring, confirmed by the values of the slip parameter [0.073 (9) A] and the fold angle [4.6 (6) degrees ]. This coordination is confirmed by NMR data, which point to the involvement of the complex in a fluxional process in solution above 285 K, passing through an intermediate involving simultaneously a metal-azaallyl and a metal-olefin bond.