The effect of solution environment and the electrostatic factor on the crystallisation of desmotropes of irbesartan

Araya-Sibaja, Andrea Mariela; Urgellés, Mariola; Vásquez-Castro, Felipe; Vargas-Huertas, Felipe; Vega-Baudrit, José; Guillén-Girón, Teodolíto; Navarro-Hoyos, Mirtha; Cuffini, Silvia Lucía

doi:10.1039/c8ra10146a

Cited by 8 publications

(10 citation statements)

References 35 publications

(56 reference statements)

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“…In fact, regarding 1 H NMR, as shown in Table 5 , signals for all protons corresponding to compound 1 have moved downfield in relation to previously reported IBS signals. 18 Furthermore, when comparing with the signals for compound 2 , the most significant changes are observed for the protons near the protonated imidazolone ring ( Figure 16 ), supporting the structure assigned for this structure ( Figure 2 ). For instance, as shown in the 1 H NMR spectra ( Figure 16 ), H-1 and H-4 from the cyclopentane near the imidazolone ring show their multiplet downfield at δ 2.14–2.30 ppm, while H-8 in the aliphatic chain shows a multiplet at δ 2.94 ppm, representing a shift increase of 0.47 ppm, and H-12 singlet moved downfield at δ 5.02 ppm.…”

Section: Resultssupporting

confidence: 64%

“…16 Irbesartan (IBS), a poorly water-soluble drug used in the treatment of hypertension, 17 exhibits desmotropy, the property of tautomers to crystallize as two different crystal structures. Recently, the effect of solvent polarity on the selectively obtained form A and form B has been investigated, 18 as well as one cationic salt and one anionic salt of IBS were successfully obtained. 19 These characteristics indicate IBS as a potentially highly diverse and numerous solid forms system.…”

Section: ■ Introductionmentioning

confidence: 99%

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Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

Araya-Sibaja¹,

Fandaruff

Guevara-Camargo

et al. 2022

ACS Omega

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The design of new pharmaceutical solids with improved physical and chemical properties can be reached through in-detail knowledge of the noncovalent intermolecular interactions between the molecules in the context of crystal packing. Although crystallization from solutions is well-known for obtaining new solids, the effect of some variables on crystallization is not yet thoroughly understood. Among these variables, solvents are noteworthy. In this context, the present study aimed to investigate the effect of ethanol (EtOH), acetonitrile (MeCN), and acetone (ACTN) on obtaining irbesartan (IBS) crystal forms with 2,3-dibromosuccinic acid. Crystal structures were solved by single-crystal diffraction, and the intermolecular interactions were analyzed using the Hirshfeld surfaces analysis. The characterization of physicochemical properties was carried out by powder X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), thermal analysis, and solution-state NMR techniques. Two different IBS salts were obtained, one from MeCN and ACTN (compound 1 ) and a different one from EtOH (compound 2 ). The experimental results were in agreement with the findings obtained through quantum mechanics continuum solvation models. Compound 1 crystallized as a monoclinic system P 2 1 / c , whereas compound 2 in a triclinic system P 1̅. In both structures, a net of strong hydrogen bonds is present, and their existence was confirmed by the FT-IR results. In addition, the IBS cation acts as a H-bond donor through the N1 and N6 nitrogen atoms which interact with the bromide anion and the water molecule O1W in compound 1 . Meanwhile, N1 and N6 nitrogen atoms interact with the oxygen atoms provided by two symmetry-related 2,3-dibromo succinate anions in compound 2 . Solution-state NMR data agreed with the protonation of the imidazolone ring in the crystal structure of compound 1. Both salts presented a different thermal behavior not only in melting temperature but also in thermal stability.

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Section: Resultssupporting

confidence: 64%

Section: ■ Introductionmentioning

confidence: 99%

Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

Araya-Sibaja¹,

Fandaruff

Guevara-Camargo

et al. 2022

ACS Omega

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“…This is reasonable because of the reaction environment (such as pH and temperature) results in two interconvertible 1H‐ and 2H‐tautomers (Scheme S2, Supporting Information). [ 13 ]…”

Section: Resultsmentioning

confidence: 99%

“…This is reasonable because of the reaction environment (such as pH and temperature) results in two interconvertible 1H-and 2H-tautomers (Scheme S2, Supporting Information). [13] To further look into the structure, the uncoordinated N atoms of two adjacent tetrazole linkers adopt an edge-to-edge arrangement with the N-N distance of 3.56 Å (Figure 1c and 2b). The suitable geometry and N-N distance render MnBTT a unique platform to chelate exogenous metal ions through PSM.…”

Section: Introductionmentioning

confidence: 99%

Design of a Metal‐Organic Framework with Preset Binding Sites for Crystallographic Visualized Metalation

et al. 2022

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Post-synthetic modification (PSM) of metal-organic frameworks (MOFs) has emerged as a powerful method to introduce diverse functional species. However, it's still a challenge to design a robust enough parent matrix with preset binding sites and simultaneously accurate structure information after PSM. In this study, a stable and highly crystalline 3D Mn-based MOF (MnBTT) is designed where two uncoordinated N atoms on adjacent linkers show appropriate distance and direction for metalation, presenting a crystallographic visualization platform for PSM. It's striking to find that the metalations occur at different positions as MnBTT are post-modified with Cu and Pd salts, respectively, and this difference can be explained by Irving-Williams series. The different metalation results bring drastic influence on their structure stability, gas adsorption capacity, and metal valence. These factors further greatly impacted their CO catalytic performance, among which Cu-modified MnBTT outperforms the others. Therefore, we demonstrate a crystallographic visualization platform with preset binding sites for metalation, shedding light on exploring new functional MOFs for broad application potential.

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“…The modeling of tautomers can also be challenging . While tautomers have been observed in many mass spectrometric experiments, − the formation process is solvent- and pH-dependent and not fully understood yet. ,, However, tautomers can be easily enumerated with commercial and open cheminformatics tools such as ChemAxon, OpenEye, RDKit, MolTPC, CDK, or AMBIT. − A fully automatic generation of tautomers using solvation models and quantum chemistry approaches is possible with CREST and the XTB software. , …”

Section: Current Applications and Real Examplesmentioning

confidence: 99%

Quantum Chemistry Calculations for Metabolomics

et al. 2021

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A primary goal of metabolomics studies is to fully characterize the small-molecule composition of complex biological and environmental samples. However, despite advances in analytical technologies over the past two decades, the majority of small molecules in complex samples are not readily identifiable due to the immense structural and chemical diversity present within the metabolome. Current gold-standard identification methods rely on reference libraries built using authentic chemical materials (“standards”), which are not available for most molecules. Computational quantum chemistry methods, which can be used to calculate chemical properties that are then measured by analytical platforms, offer an alternative route for building reference libraries, i.e. , in silico libraries for “standards-free” identification. In this review, we cover the major roadblocks currently facing metabolomics and discuss applications where quantum chemistry calculations offer a solution. Several successful examples for nuclear magnetic resonance spectroscopy, ion mobility spectrometry, infrared spectroscopy, and mass spectrometry methods are reviewed. Finally, we consider current best practices, sources of error, and provide an outlook for quantum chemistry calculations in metabolomics studies. We expect this review will inspire researchers in the field of small-molecule identification to accelerate adoption of in silico methods for generation of reference libraries and to add quantum chemistry calculations as another tool at their disposal to characterize complex samples.

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The effect of solution environment and the electrostatic factor on the crystallisation of desmotropes of irbesartan

Abstract: The experimental conditions necessary for stabilising irbesartan (IBS) tautomers in solution and selectively obtaining the desmotropic crystal forms are presented herein.

Cited by 8 publications

References 35 publications

Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

Design of a Metal‐Organic Framework with Preset Binding Sites for Crystallographic Visualized Metalation

Quantum Chemistry Calculations for Metabolomics

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