Solubility and solvation free energy of a cardiovascular drug, LASSBio-294, in ionic liquids: A computational study

Dasari, Sathish; Mallik, Bhabani S.

doi:10.1016/j.molliq.2020.112449

Cited by 39 publications

(22 citation statements)

References 78 publications

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“…The contributions of electrostatic and non-electrostatic interactions to the solvation free energy are comparable in two heterodimers; however, a slight predominance of non-electrostatic interactions was observed in the case of VAL/NIC2. It has been reported that non-electrostatic interactions, such as van der Waals interactions, play a major role in solubilizing the pharmaceuticals, which further confirms the assumption that the VAL/NIC2 heterodimer may have a greater solubility than the VAL/NIC1. Moreover, in the case of the VAL/NIC2 heterodimer, the difference in dipole moment values in the gas phase and ethanol has been observed.…”

Section: Resultssupporting

confidence: 70%

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential

et al. 2021

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Physicochemical properties, in particular solubility and the associated bioavailability, are key factors in determining efficacy of poorly water-soluble drugs, which constitute 40% of new drugs in the market, and improving them is an important challenge for modern pharmacy. A recent strategy to achieve this goal is formation of stable co-amorphous solid dispersions with co-formers of low molecular weight. Here, the amorphization strategy was applied for low-soluble anti-hypertensive valsartan (VAL), an angiotensin II receptor blocker, and nicotinamide, which exhibits lung- and cardio-protective effects. Through interactions with the renin–angiotensin–aldosteron system, VAL may be used to treat both hypertension and the current pandemic coronavirus SARS-CoV-2 infection. Using mechanochemical and liquid- and solid-state approaches, solvated co-amorphous solid dispersions of VAL with nicotinamide were obtained. They were characterized by spectroscopic, thermal, and X-ray analyses. The density functional theory, quantum theory of atoms in molecules, and non-covalent interaction index calculations revealed the presence of two types of hydrogen bonds between VAL and NIC (i.e., N–H···O and O–H···O). One of them had a partially covalent character, which caused conformational changes in the flexible VAL molecule, restricting contribution of the tetrazolyl N–H donor and thus limiting the possibility of co-crystal formation. The recognized VAL/NIC1- and VAL/NIC2-type heterodimeric interactions were responsible for the excellent durability of the solid compositions and up to 24-fold better solubility than VAL alone. The synthesized dispersions constitute a new class of dually acting drugs, containing an active pharmaceutical ingredient (VAL) and supporting nutraceutical (nicotinamide).

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Section: Resultssupporting

confidence: 70%

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential

et al. 2021

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“…Details of its definition and calculation approach were introduced in the existing literatures. 41,42,71,72 , implying that π-π stacking interaction is important contributions to the good solubility of etomidate in imidazolium-based ILs. 30,73,74 However, etomidate solubility in [Emim]…”

Section: π-π Stacking Interactionmentioning

confidence: 99%

“…However, our previous simulation results confirmed that H-bond interaction between ibuprofen and anions was the most dominant interaction for the superior solubility of ibuprofen in ILs, followed by favorable π-π stacking interaction of ibuprofen with imidazolium cations. 41 The recent MD study of Mallik et al 42 revealed that the excellent solubility of a cardiovascular drug in seven ILs was chiefly determined by van der Waals (vdW) interaction. Alternatively, the DFT calculations conducted by Ding et al 43 found that ILs with efficient separation of chiral amlodipine should possess strong H-bond interactions from both cations and anions.…”

Section: Introductionmentioning

confidence: 99%

The role of hydrogen‐bond in solubilizing drugs by ionic liquids: A molecular dynamics and density functional theory study

Huang

Ouyang

2022

AIChE Journal

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The solvation mechanisms of aspirin and etomidate in four combinations of [Emim]+ and [BuGun]+ paired with [OAc]− and [NTf2]− were systematically studied by molecular dynamics simulations and DFT calculations. It was shown that the favorable solvation of aspirin and etomidate correlated well with hydrogen‐bond (H‐bond) basicity of anions and the H‐bond acidity of cations, respectively. Wherein, the H‐bond between aspirin and [OAc]− anion with high H‐bond basicity possessed covalent feature, so ILs containing [OAc]− anion has the best effective in solubilizing aspirin. However, H‐bond interactions between etomidate and cations exhibited an electrostatic dominant, and moderate cation–anion interaction could weaken it. Accordingly, for etomidate, the best ILs solvent comprised a weakly interacting anion and a cation with strong H‐bond acidity, that is, [BuGun][NTf2]. This solvation difference was because aspirin with carboxyl group displayed strongly H‐bond donating characteristic, whereas etomidate with no active hydrogen protons mainly formed H‐bond with cations. Additionally, we found that π–π stacking interactions were of secondary importance for the solubilization of etomidate, but little for aspirin. These simulations will be helpful for experimental design new ILs to solubilize some drugs with aspirin‐like or etomidate‐like structures.

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“…Molecular dynamics simulations have been used to analyze the interaction between LASSBio‐294, a cardiovascular drug, and ILs, allowing for a higher throughput screen method than wet lab experiments can allow. [ 43 ] A summary of the publications covered in this section can be found in Table S2 , Supporting Information. Overall, a variety of ILs are being used to substantially increase the aqueous solubility of otherwise sparingly soluble pharmaceutical candidates, and this process is largely driven by the ILs interacting with the drug molecules.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Recent Advances in Ionic Liquids in Biomedicine

2021

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The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task-specific solvents.

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Solubility and solvation free energy of a cardiovascular drug, LASSBio-294, in ionic liquids: A computational study

Cited by 39 publications

References 78 publications

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential

Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential

The role of hydrogen‐bond in solubilizing drugs by ionic liquids: A molecular dynamics and density functional theory study

Recent Advances in Ionic Liquids in Biomedicine

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