Synthesis, crystal structure, hirshfeld surface analysis, spectral and quantum chemical studies of pharmaceutical cocrystals of a bronchodilator drug (Theophylline)

Novena, L. Mary; Athimoolam, S.; Anitha, R.; Bahadur, S. Asath

doi:10.1016/j.molstruc.2021.131585

Cited by 22 publications

(3 citation statements)

References 37 publications

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“…Therefore, compared with form I, water molecules are more likely to compete with FA molecules for THP molecules to form the optimal hydrogen bond structure in form II. The weaker hydrogen bond of form II is also one of the reasons for the higher solubility of form II . In form II, the disintegration of homologous hydrogen-bonding aggregates for FA (Figures a and) results in more hydrophilic functional groups (CO and N–H) populated on the (001) and (010) planes (Figure S8 right) .…”

Section: Resultsmentioning

confidence: 99%

“…The weaker hydrogen bond of form II is also one of the reasons for the higher solubility of form II. 61 In form II, the disintegration of homologous hydrogen-bonding aggregates for FA (Figures 2a and4) results in more hydrophilic functional groups (C�O and N−H) populated on the (001) and (010) planes (Figure S8 right). 7 The hydrophilic functional groups in form I are difficult to contact and interact with water molecules because of the hydrophobic methoxy group on the plane of form I (Figure S8 left).…”

Section: Solubility and Idr Resultsmentioning

confidence: 99%

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Two Polymorphic Cocrystals of Theophylline with Ferulic Acid

Liu

Chan²,

et al. 2023

Crystal Growth & Design

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In this study, the crystal structures of 1:1 theophylline–ferulic acid cocrystal polymorphs are reported for the first time. Interestingly, both forms crystallize in the same space group but with a different number of molecules in the asymmetric unit (form I = 2; form II = 4). The two polymorphs show distinct crystal morphology, demonstrating prism and rod single crystals, respectively. Theoretical calculations are performed to predict their morphology and thermodynamic stability (form I > form II). The prediction result agrees well with the measured pharmaceutical properties. Form I presents better hygroscopic stability (RH < 95%), slower dissolution, and lower solubility (1.06 ± 0.03, 1.63 ± 0.01, 1.30 ± 0.08 and 4.09 ± 0.05 mg/mL in water, pH = 1.2, pH = 4.5 and pH = 6.8 buffered solutions) over form II (8.45 ± 0.33, 2.41 ± 0.17, 3.46 ± 0.26 and 28.71 ± 0.87 mg/mL in water, pH = 1.2, pH = 4.5 and pH = 6.8 buffered solutions). In summary, this work elucidates the experimental findings with relevant predictions systematically and enriches our understanding of the structure–property relationship of the theophylline cocrystal system.

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Section: Resultsmentioning

confidence: 99%

Section: Solubility and Idr Resultsmentioning

confidence: 99%

Two Polymorphic Cocrystals of Theophylline with Ferulic Acid

Liu

Chan²,

et al. 2023

Crystal Growth & Design

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“…The XRD characterization of the theophylline molecule revealed strong interactions within crystal structures, such as, C-H⋯π, C=O⋯H and N⋯H⋯O (Fig. 3) [27].…”

Section: Structurementioning

confidence: 99%

Synthesis of Pincer type carbene and their Ag(I)-NHC complexes, and their Antimicrobial activities

Türkyılmaz

Ateş

2022

Journal of Sustainable Construction Materials and Technologies

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In this study, theophylline (1) compounds were synthesized with addition of 2-bromoetha-nol, 2-bromoacetamide and methyl-2-bromoacetate to attain symmetric connections to NHCs (2a–c). New complexes containing the symmetric N-heterocyclic carbene (NHC) ligands were synthesized using azolium salts in dimethyl formamide (DMF). After the NHC predecessor compounds reacted with Ag2O, Ag(I)-NHC complexes were synthesized in the following: 7,9-di-(2-hydroxyethyl)-8,9-dihydro-1,3-dimethyl-1H-purine-2,6(3H,7H)-dionedium silver(I)bromide (3a), 7,9-di(acetamide)-8,9-dihydro-1,3-dimethyl-1H-purine-2,6(3H,7H)-di-ondium silver(I)bromide (3b) and 7,9-di(methylacetate)-8,9-dihydro-1,3-dimethyl-1H-pu-rine-2,6(3H,7H)-diondiumsilver(I)bromide (3c). Both synthesized NHC predecessors (2a-c) and Ag(I)-NHC complexes (3a-c) were described by FTIR, 1H-NMR, 13C-NMR, liquid and solid-state conductivity values, TGA analysis, melting point analysis and XRD spectroscopy. In-vitro antibacterial activities of NHC-predecessors and Ag(I)-NHC complexes were tested against gram-positive bacteria (Staphylococcus Aureus and Bacillus Cereus), gram-negative bacteria (Escherichia Coli and Listeria Monocytogenes), and fungus (Candida Albicans) in Tryptic Soy Broth method. Ag(I)-NHC complexes showed higher antibacterial activity than pure NHC predecessors. The lowest microbial inhibition concentration (MIC) value of compound 3a was obtained as 11.56 μg/ml for Escherichia Coli and 11.52 μg/ml for Staphylococcus Aureus. All tested complexes displayed antimicrobial activity with different results.

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Combinatory Effect of Gemcitabine and 5‐Fluorouracil Investigated Through Chemoinformatics and Molecular Dynamics Simulation Against Breast Cancer

Sukumaran,

Zochedh,

Chandran

et al. 2024

Int J of Quantum Chemistry

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Co‐delivering FDA‐approved drugs can be less harmful and boost biological activity by targeting different protein mechanism at same time. Gemcitabine and 5‐Fluorouracil (GE5F) adduct work together to destroy cancer cells and increase the efficacy in the fight against breast cancer. The basis set B3LYP/6‐311 G was utilized in this investigation to improve the structure of GE5F adduct. The natural bond analysis exhibited the intermolecular interactions of the GE5F adduct. Electronic transitions were seen to be π → π*, and theoretical calculations were performed for the ultraviolet to visible spectrum. The energy gap between HOMO and LUMO was used to study the GE5F adduct's structural stability and reactivity; the computed energy gap (ΔE) was 3.912 eV. The Mulliken charge population was assessed and the complex structure's electrostatic potential was established. Weak interactions of the GE5F were assessed using RDG analysis, and topological aspects were investigated using LOL and ELF analysis. Investigating the GE5F adduct's adsorption, distribution, metabolism, excretion, and toxicity properties, the results confirmed that GE5F adduct comes under the safety parameters being a drug‐likeness molecule. Molecular docking experiments were conducted using target proteins for breast cancer. The complex molecule had a higher binding affinity as indicated by the docking scores, which validated the better combinatorial interaction between gemcitabine and 5‐Fluorouracil. With − 9.4 kcal/mol, the complex molecule's strongest binding capacity was against PARP protein, and stable confirmation was observed through molecular dynamic simulation for 100 ns with four hydrogen bond interactions. These in silico finding will pave a way for in vitro and in vivo experiments with better enhancement of FDA approved drugs.

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Synthesis, crystal structure, hirshfeld surface analysis, spectral and quantum chemical studies of pharmaceutical cocrystals of a bronchodilator drug (Theophylline)

Cited by 22 publications

References 37 publications

Two Polymorphic Cocrystals of Theophylline with Ferulic Acid

Two Polymorphic Cocrystals of Theophylline with Ferulic Acid

Synthesis of Pincer type carbene and their Ag(I)-NHC complexes, and their Antimicrobial activities

Combinatory Effect of Gemcitabine and 5‐Fluorouracil Investigated Through Chemoinformatics and Molecular Dynamics Simulation Against Breast Cancer

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