Conformation of the umifenovir cation in the molecular and crystal structures of four carboxylic acid salts

Orola, Lia̅na; Sarceviča, Inese; Kons, Artis; Actiņš, Andris; Veidis, Mikelis V.

doi:10.1016/j.molstruc.2013.10.010

Cited by 10 publications

(18 citation statements)

References 19 publications

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“…As expected, arbidol and maleic acid form a salt, which crystallizes in the triclinic Pī space group with one arbidol cation and one maleate anion in the asymmetric unit. The structure is in good agreement with that reported by Orola et al, who, however, collected diffraction data at 293 K [22]. In this work, single-crystal X-ray experiment was carried out at low temperature (180 K), and the crystal structure of the [Arb + Mlc] salt was refined.…”

Section: Crystal Structuressupporting

confidence: 88%

“…Arbidol base was prepared according to the procedure described by Orola et al [22]. Maleic acid (C4H4O4, 99%), fumaric acid (C4H4O4, 99%), and succinic acid (C4H6O4, 99%) were purchased from Acros Organics.…”

Section: Compounds and Solventsmentioning

confidence: 99%

“…It is known that in order to maintain the concentration of active substance in the blood above the therapeutic threshold, arbidol should be taken by one dose every 3-4 h for several days, including night time, which makes effective treatment more difficult [19]. Therefore, researchers are still trying to find a new crystal form of Arb with improved solubility parameters [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…All the co-formers produced new crystal forms. The crystal structure of [Arb + Mlc] was previously solved by single crystal X-ray diffraction at 298 K [22]. We redetermined the salt form by single crystal X-ray diffraction at 180 K. Herein, we report the preparation of two salts and one cocrystal with three dicarboxylic acids: arbidol-maleate salt (1:1), arbidol-fumarate salt (2:1), and arbidol-succinic acid cocrystal (1:1) with arbidol in its zwitterionic form.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

et al. 2015

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Salts of the antiviral drug arbidol (umifenovir) (Arb) with maleate (Mlc) and fumarate (Fum) anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrystal in zwitterion form with succinic acid (Suc) has also been found and characterized. The arbidol zwitterion was not previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Analysis of the conformational preferences of the arbidol molecule in the crystal structures has shown that it adopts two types of conformations, namely "open" and "closed" ones. Thermal stability of the arbidol salts and cocrystal have been analyzed by means of differential scanning calorimetry, thermogravimetric, and mass-spectrometry analysis. The dissolution study of the arbidol salts and cocrystal performed in aqueous buffer solutions with pH 1.2 and 6.8 has shown that both the salts and the cocrystal dissolve incongruently to form an arbidol hydrochloride monohydrate at pH 1.2 and an OPEN ACCESSCrystals 2015, 5 651 arbidol base at pH 6.8, respectively. The cocrystal reaches the highest solubility level in both pH 1.2 and pH 6.8 solutions.

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Section: Crystal Structuressupporting

confidence: 88%

Section: Compounds and Solventsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

et al. 2015

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“…The purity with respect to polymorphic forms was evaluated using PXRD by comparing to the theoretical diffraction pattern simulated from crystal structure data [10].…”

Section: Methodsmentioning

confidence: 99%

Characterization and Physicochemical Evaluation of Molecular Complexes Formed Between Umifenovir and Dicarboxylic Acids

Kons¹,

Be̅rziņš²,

Krūkle-Bērziņa³

et al. 2014

Latvian Journal of Chemistry

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The paper reports the investigation of three umifenovir molecular complexes with dicarboxylic acids, prepared to improve the bioavailability of this drug. All three molecular complexes were investigated by powder X-ray diffraction, infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. The solubility and thermal properties were determined as well. Polymorph and solvate screening of umifenovir molecular complexes were performed by recrystallization from various solvents, as well as neat and solvent-drop grinding.

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Synthesis and Experimental Studies on Supramolecular Synthons of Aminoguanidinium Carboxylates: A Case Study of π‐HoleBonded Carbon Bonding via Theoretical Approaches

et al. 2018

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New supramolecular salts of aminoguanidinium with mono and di-carboxylic acids (formate and maleate respectively) have been prepared and their crystal structures were solved using single crystal X-ray diffraction analysis. A crystal packing of both the ion pair assemblies are organized via various weak intermolecular interactions including NÀ H…O, OÀ H…O, CÀ H… O and NÀ H…N etc., hydrogen bonds and form 2D and 3D assemblies. The supramolecular viewpoint of the titled ion-pair assemblies are discussed interms of strong hydrogen bonded ring motifs generated between the aminoguanidininium and carboxylates and the homo synthons of aminoguanidine retained in these solid state assemblies. Interestingly both the ion pair assemblies are supported by the π-hole utilized carbon bonding (C…O, C…N &C…C) interactions. As compared to aminoguanidinium formate assembly, in amminoguanidinium hydrogenmaleate, π-hole utilized carbon bonding interactions were sustained between the cation and anion pair which affords the spatial arrangement for stacking the cation and anion through electrostatic interaction. In this respect, πhole interactions are function as a structure directing self-assembled force and regulate the aminoguandinium hydrogen maleate assembly. Apart from the X-ray diffraction studies, the geometrical parameters, interaction energy, its energy component contribution (LMOEDA analysis) and also the properties of weak interactions including carbon bonding present in the synthesized aminoguanidinium carboxylates assembly were analyzed systematically through wave functional analysis with MP2/6-31 + + g(d,p) level of theory. The role of hydrogen bonding and carbon bonding confirmation and their strength in terms of crystal packing were summarized through various theoretical calculations such as Atoms In Molecules (AIM), Hirshfeld surface analysis, NCI plot and Natural Bonding Orbital analysis (NBO).

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Conformation of the umifenovir cation in the molecular and crystal structures of four carboxylic acid salts

Cited by 10 publications

References 19 publications

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

Characterization and Physicochemical Evaluation of Molecular Complexes Formed Between Umifenovir and Dicarboxylic Acids

Synthesis and Experimental Studies on Supramolecular Synthons of Aminoguanidinium Carboxylates: A Case Study of π‐HoleBonded Carbon Bonding via Theoretical Approaches

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