Experimental and Theoretical Investigation of Hydrogen-Bonding Interactions in Cocrystals of Sulfaguanidine

Huang, Shan; Cheemarla, Vinay K. R.; Tiana, Davide; Lawrence, Simon E.

doi:10.1021/acs.cgd.2c01337

Cited by 11 publications

(4 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Note that the nomenclature for the forms is not consistent, and one of the two hydrates was solved as two different tautomers (amino and imino). Furthermore, cocrystals of SGD with thiobarbituric acid (anhydrate and hydrate), 1,10-phenanthroline, antipyrine, 4-nitrobenzoic acid (anhydrate and acetonitrile solvate), 3-nitrobenzoic acid, phenazine, and 1,2-di(pyridyl)ethylene have been reported.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Widauer,

Petrick,

Braun

2024

Crystal Growth & Design

View full text Add to dashboard Cite

A thorough re-examination of sulfaguanidine’s (SGD) solid-state behavior was conducted, 65 years after the initial report on SGD polymorphism. This investigation focuses on the polymorphic nature of the compound, the formation of hydrates and solvates, and the pivotal role of experimental and computational methods in screening, assessing stability, and understanding transformation processes. The findings confirm the presence of five anhydrates (AH-I–V), two monohydrate polymorphs (Hy1-I and Hy1-II), and nine solvates (with tetrahydrofuran, methanol, ethanol, t-butanol, acetone, cyclohexanone, dimethyl sulfoxide, dimethyl formamide, and dimethyl acetamide). Notably, nine novel structures–two anhydrates and seven solvates–are reported, solved from powder X-ray diffraction data. Calorimetric measurements have revealed that AH-II is the thermodynamically stable polymorph at room and low temperatures. In contrast, AH-I emerges as the stable polymorph at higher temperatures, yet it exhibits remarkable kinetic stability at RT and demonstrates greater stability in terms of hydration. The anhydrate forms exhibit distinctive packing arrangements, while the two hydrates share a close structural resemblance. Among the seven structurally characterized solvates, only the tetrahydrofuran and dimethyl sulfoxide solvates are isostructural. Controlled desolvation experiments enabled the formation of AH-I, AH-II, and, notably, AH-V for the first time. The anhydrate and monohydrate crystal structure prediction studies reveal that the computed lowest-energy structures correspond to experimentally observed forms and propose models for the elusive AH-IV structure. Overall, the exploration of SGD’s solid-state landscape confirms a rich array of highly stable H-bonding motifs and packing arrangements, positioning this study as an ideal model for complex solid-state systems and shedding light on its intricate solid-state nature.

show abstract

Section: Introductionmentioning

confidence: 99%

Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Widauer,

Petrick,

Braun

2024

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…This energy can be determined through the equation E HB = ½ V BCP . Recognizing the limitations of the QTAIM analysis in identifying all anticipated weak non-covalent interactions, particularly intramolecular hydrogen bonds, the NCI approach was employed as an additional method 44 . This study facilitates the visualization of regions involved in either repulsive or attractive interactions.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, characterization, biological potency, and molecular docking of Co2+, Ni2+ and Cu2+ complexes of a benzoyl isothiocyanate based ligand

Al-Farraj,

Younis,

El-Reash

2024

Sci Rep

View full text Add to dashboard Cite

The primary objective of the present study was to produce metal complexes of H4DAP ligand (N,N'-((pyridine-2,6-diylbis(azanediyl))bis(carbonothioyl))dibenzamide) derived from 2,6-diaminopyridine and benzoyl isothiocyanate with either ML or M2L stoichiometry. There are three distinct coordination complexes obtained with the formulas [Co(H2DAP)]·H2O, [Ni2(H2DAP)Cl2(H2O)2]·H2O, and [Cu(H4DAP)Cl2]·3H2O. The confirmation of the structures of all derivatives was achieved through the utilization of several analytical techniques, including FT-IR, UV–Vis, NMR, GC–MS, PXRD, SEM, TEM analysis, and QM calculations. Aiming to analyze various noncovalent interactions, topological methods such as QTAIM, NCI, ELF, and LOL were performed. Furthermore, the capacity of metal–ligand binding was examined by fluorescence emission spectroscopy. An in vitro investigation showed that the viability of MDA-MB-231 and HepG-2 cells was lower when exposed to the manufactured Cu2+ complex, in comparison to the normal cis-platin medication. The compounds were further evaluated for their in vitro antibacterial activity. The Ni2+ complex has shown promising activity against all tested pathogens, comparable to the reference drugs Gentamycin and Ketoconazole. Furthermore, a computational docking investigation was conducted to further examine the orientation, interaction, and conformation of the recently created compounds on the active site of the Bcl-2 protein.

show abstract

“…49 SG, also a sulfonamide, acts locally in the gastrointestinal tract against bacterial pathogens and is commonly employed in animal treatment. 50 Five polymorphic forms (I, 51 II, 52 III, 51 IV, 53 and V 51,53 ), two monohydrate forms, 54,55 nine solvates, 53 and cocrystals with antipyrine, 56 1,10-phenantholine, 57 thiobarbituric acid, 57 1,2-di(4-pyridyl)ethylene, 58 4-nitrobenzoic acid, 58 3-nitrobenzoic acid, 58 and phenazine 58 are reported.…”

Section: Introductionmentioning

confidence: 99%

Flavone Cocrystals: A Comprehensive Approach Integrating Experimental and Virtual Methods

Petrick,

Grünwald,

Braun

2024

Crystal Growth & Design

View full text Add to dashboard Cite

The dapsone/flavone cocrystal system served as a benchmark for both experimental and virtual screening methods. Expanding beyond this, two additional active pharmaceutical ingredients (APIs), sulfanilamide and sulfaguanidine, structurally related to dapsone were chosen to investigate the impact of substituents on cocrystal formation. The experimental screening involved mechanochemical methods, slurry experiments, hot-melt extrusion, and the contact preparation method. The virtual screening focused on crystal structure prediction (CSP), molecular complementarity, hydrogen-bond propensity, and molecular electrostatic potentials. The CSP studies not only indicated that each of the three APIs should form cocrystals with flavone but also reproduced the known single-and multicomponent phases. Experimentally, dapsone/flavone cocrystals A CC , B CC , C CC , and D CC were reproduced, C CC was identified as a nonstoichiometric hydrate, and a fifth cocrystal (E CC ), a t-butanol solvate, was discovered. The cocrystal polymorphs A CC and B CC are enantiotripically related, and D CC , exhibiting a different stoichiometric ratio, is enthalpically stabilized over the other cocrystals. For the sulfaguanidine/flavone system, two novel, enantiotripically related cocrystals were identified. The crystal structures of two cocrystals and a flavone polymorph were solved from powder X-ray diffraction data, and the stability of all cocrystals was assessed through differential scanning calorimetry and lattice energy calculations. Despite computational indications, a diverse array of cocrystallization techniques did not result in a sulfanilamide/flavone cocrystal. The driving force behind dapsone's tendency to cocrystallize with flavone can be attributed to the overall strength of flavone interactions in the cocrystals. For sulfaguanidine, the potential to form strong API•••API and API••• coformer interactions in the cocrystal is a contributing factor. Furthermore, flavone was found to be trimorphic.

show abstract

Experimental and Theoretical Investigation of Hydrogen-Bonding Interactions in Cocrystals of Sulfaguanidine

Cited by 11 publications

References 72 publications

Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Comprehensive Insights into Sulfaguanidine in the Solid State: An Experimental and Computational Study

Synthesis, characterization, biological potency, and molecular docking of Co2+, Ni2+ and Cu2+ complexes of a benzoyl isothiocyanate based ligand

Flavone Cocrystals: A Comprehensive Approach Integrating Experimental and Virtual Methods

Contact Info

Product

Resources

About