Polymorphic Ammonium Salts of the Antibiotic 4-Aminosalicylic Acid

Reaction of the antibiotic 4-aminosalicylic acid with ammonia yields three polymorphic forms of the ammonium 4-aminosalicylate salt [NH₄]­[C₆H₃NH₂OH­(COO)]. When the reaction is conducted in solution, the three polymorphs are obtained concomitantly, while liquid-assisted grinding and solid–gas reaction result in the formation of pure Form II. The three polymorphs are characterized by different patterns of hydrogen bonding interactions between the structurally rigid anions and the ammonium cations. Solid products were characterized by single-crystal and powder X-ray diffraction, variable temperature powder diffraction, calorimetric techniques (DSC and TGA), and hot-stage microscopy (HSM)

Polymorphic Ammonium Salts of the Antibiotic 4-Aminosalicylic Acid

Reaction of the antibiotic 4-aminosalicylic acid with ammonia yields three polymorphic forms of the ammonium 4-aminosalicylate salt [NH₄]­[C₆H₃NH₂OH­(COO)]. When the reaction is conducted in solution, the three polymorphs are obtained concomitantly, while liquid-assisted grinding and solid–gas reaction result in the formation of pure Form II. The three polymorphs are characterized by different patterns of hydrogen bonding interactions between the structurally rigid anions and the ammonium cations. Solid products were characterized by single-crystal and powder X-ray diffraction, variable temperature powder diffraction, calorimetric techniques (DSC and TGA), and hot-stage microscopy (HSM)

Dicarboxylate Recognition Properties of a Dinuclear Copper(II) Cryptate

A ditopic polyamine macrobicyclic compound with biphenylmethane spacers was prepared, and its dinuclear copper­(II) complex was studied as a receptor for the recognition of dicarboxylate anions of varying chain length in H₂O/MeOH (50:50 (v/v)) solution. The acid–base behavior of the compound, the stability constants of its complexes with Cu²⁺ ion, and the association constants of the copper­(II) cryptate with succinate (suc^2–), glutarate (glu^2–), adipate (adi^2–), and pimelate (pim^2–) were determined by potentiometry at 298.2 ± 0.1 K in H₂O/MeOH (50:50 (v/v)) and at ionic strength 0.10 ± 0.01 M in KNO₃. The association constants of the same cryptate as receptor for aromatic dicarboxylate substrates, such as phthalate (ph^2–), isophthalate (iph^2–), and terephthalate (tph^2–), were determined through competition experiments by spectrophotometry in the UV region. Remarkably high values of association constants in the range of 7.34–10.01 log units were found that are, to the best of our knowledge, the highest values of association constants reported for the binding of dicarboxylate anions in aqueous solution. A very well defined peak of selectivity was observed with the binding constant values increasing with the chain length and reaching the maximum for substrates with four carbon atoms between the carboxylate groups. Single-crystal X-ray diffraction determinations of the cascade complexes with adi^2– and tph^2– assisted in the understanding of the selectivity of the cryptate toward these substrates. The Hirshfeld surface analyses of both cascade complexes suggest that the establishment of several van der Waals interactions between the substrates and the walls of the receptor also contributes to the stability of the associations

Polymorphic Ammonium Salts of the Antibiotic 4-Aminosalicylic Acid

Reaction of the antibiotic 4-aminosalicylic acid with ammonia yields three polymorphic forms of the ammonium 4-aminosalicylate salt [NH₄]­[C₆H₃NH₂OH­(COO)]. When the reaction is conducted in solution, the three polymorphs are obtained concomitantly, while liquid-assisted grinding and solid–gas reaction result in the formation of pure Form II. The three polymorphs are characterized by different patterns of hydrogen bonding interactions between the structurally rigid anions and the ammonium cations. Solid products were characterized by single-crystal and powder X-ray diffraction, variable temperature powder diffraction, calorimetric techniques (DSC and TGA), and hot-stage microscopy (HSM)

Expanding the Pool of Multicomponent Crystal Forms of the Antibiotic 4‑Aminosalicylic Acid: The Influence of Crystallization Conditions

Finding new multicomponent crystal forms of commercially available pharmaceuticals is important, as they represent a straightforward way to drastically influence the solid-state properties of a drug. The antibiotic 4-aminosalicylic acid (ASA) is known to exist in several multicomponent crystal forms, and in this work we expand the world of ASA cocrystals and salts by reporting new crystalline forms comprising diazabicyclo[2.2.2]­octane (DABCO), and caffeine. All species were characterized by X-ray single crystal, powder diffraction, and thermal behavior. This study contributes to the rationalization of preferred functional groups for the synthesis of 4-aminosalicylic acid new multicomponent crystal forms and highlights the relevance of the reaction conditions in the achievement of those forms

Gabapentin Coordination Networks: Mechanochemical Synthesis and Behavior under Shelf Conditions

Active pharmaceutical ingredients (API) coordination complexes and networks present a promising pathway for developing new bioinspired materials. In the present study, we report several coordination networks of gabapentin with Y­(III), Mn­(II), and several lanthanides (LnCl₃), Ln = La³⁺, Ce³⁺, Nd³⁺, Er³⁺ obtained by mechanosynthesis. To the best of our knowledge, these are among the first coordination networks of pharmaceuticals involving lanthanides. These novel compounds proved to be unstable under shelf conditions, are thermally stable until water release at approximately 80 °C, and decompose above 200–250 °C. The coordination networks obtained present different structural architectures based on mono-, di-, tri-, and hexa-metallic centers (herein called monomers, dimers, trimers, and hexamers), and also a one-dimensional polymeric chain was obtained. Gabapentin chelation modes are the same in most of the networks, adopting three typical geometries: the bidentate coordination – chelation, mode I; the bridge coordination, mode II, and the “bidentate-bridge” coordination, mode III. NMR studies show that the compounds have different behavior in solution, where a single coordination mode seems to be present

12,17-Cyclojatrophane and Jatrophane Constituents of <i>Euphorbia welwitschii</i>

Euphowelwitschines A (<b>1</b>) and B (<b>2</b>), isolated from a methanolic extract of <i>Euphorbia welwitschii</i>, exhibit a rare combination of structural features in having a 5/8/8 fused-ring system and a 12,15-ether bridge. Moreover, the isolation of the additional new compounds welwitschene (<b>3</b>) and epoxywelwitschene (<b>4</b>) has provided insights into the biogenetic pathway of 12,17-cyclojatrophanes. The structures of <b>1</b>–<b>4</b> were determined by spectroscopic methods inclusive of 1D and 2D NMR experiments and X-ray crystallography for compounds <b>1</b> and <b>2</b>. Preliminary information on the selective antiproliferative activity of compounds <b>1</b>–<b>4</b> is also described

New Tetracopper(II) Cubane Cores Driven by a Diamino Alcohol: Self-assembly Synthesis, Structural and Topological Features, and Magnetic and Catalytic Oxidation Properties

Two new coordination compounds with tetracopper­(II) cores, namely, a 1D coordination polymer, [Cu₄(μ₄-H₂edte)­(μ₅-H₂edte)­(sal)₂]_<i>n</i>·10<i>n</i>H₂O (<b>1</b>), and a discrete 0D tetramer, [Cu₄(μ₄-Hedte)₂(Hpmal)₂(H₂O)]·7.5H₂O (<b>2</b>), were easily self-assembled from aqueous solutions of copper­(II) nitrate, <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetrakis­(2-hydroxyethyl)­ethylenediamine (H₄edte), salicylic acid (H₂sal), or phenylmalonic acid (H₂pma). The obtained compounds were characterized by IR and electron paramagnetic resonance spectroscopy, thermogravimetric and elemental analysis, and single-crystal X-ray diffraction. In addition to different dimensionalities, their structures reveal distinct single-open [Cu₄(μ₂-O)­(μ₃-O)₃] (in <b>1</b>) or double-open [Cu₄(μ₂-O)₂(μ₃-O)₂] (in <b>2</b>) cubane cores with 3M4-1 topology. In crystal structures, numerous crystallization water molecules are arranged into the intricate infinite 1D {(H₂O)₁₈}_<i>n</i> water tapes (in <b>1</b>) or discrete (H₂O)₉ clusters (in <b>2</b>) that participate in multiple hydrogen-bonding interactions with the metal–organic hosts, thus extending the overall structures into very complex 3D supramolecular networks. After simplification, their topological analysis revealed the binodal 6,10- or 6,8-connected underlying 3D nets with unique or rare 6,8T2 topology in <b>1</b> and <b>2</b>, respectively. The magnetic properties of <b>1</b> and <b>2</b> were investigated in the 1.8–300 K temperature range, indicating overall antiferromagnetic interactions between the adjacent Cu^II ions within the [Cu₄O₄] cores. The obtained compounds also act as bioinspired precatalysts for mild homogeneous oxidation, by aqueous hydrogen peroxide at 50 °C in an acidic MeCN/H₂O medium, of various cyclic and linear C₅–C₈ alkanes to the corresponding alcohols and ketones. Overall product yields of up to 21% (based on alkane) were achieved, and the effects of various reaction parameters were studied

Molecular Salts of l‑Carnosine: Combining a Natural Antioxidant and Geroprotector with “Generally Regarded as Safe” (GRAS) Organic Acids

The potent natural hydrophilic antioxidant l-carnosine has been reacted with a number of organic acids belonging to the “generally regarded as safe” (GRAS) group, resulting in the preparation of 11 new crystalline salts, which were characterized by X-ray powder diffraction and thermal analysis; the structures of six of them were determined from powder data, and one was fully characterized via single crystal data. The reaction with folic acid resulted in an amorphous folate salt, which was characterized by a combination of thermal methods and Raman spectroscopy; the solubility of the folate salt was also measured and found to be comparable to that of the commercial sodium folate

Inhibition of the STAT3 Protein by a Dinuclear Macrocyclic Complex

A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing <i>m</i>-xylyl spacers, L, was prepared, and its dinuclear copper­(II) and zinc­(II) complexes were used as receptors for the recognition in aqueous solution of a phosphorylated peptide derived from a sequence of the STAT3 protein. A detailed study of the acid–base behavior of L and of its complexation properties as well as of the association of the phosphorylated peptide to the receptor was carried out by potentiometry in aqueous solution at 298.2 K and <i>I</i> = 0.10 M in KNO₃. The data revealed that the receptor forms stable associations with several protonated forms of the substrate, with constant values ranging from 3.32 to 4.25 log units. The affinity of the receptor for the phosphorylated substrate studied is higher at a pH value where the receptor is mainly in the [Cu₂L]⁴⁺ form and the pY residue of the substrate is in the dianionic form (pH 6.55). These results, also supported by ³¹P NMR studies, showed that the phosphopeptide is bound through the phosphoryl group in a bridging mode. Additionally, the receptor inhibited binding between active (phosphorylated) STAT3 and its target DNA sequence in a dose-dependent manner (IC₅₀ 63 ± 3.4 μM) in human nuclear extracts in vitro. Treatment of whole cells with the inhibitor revealed that it is bioactive in living cells and has oncostatic properties that could be interesting for the fight against cancer and other pathologies involving the STAT3 protein