Inclusion complexation and liposomal encapsulation of an isoniazid hydrazone derivative in cyclodextrin for pH-dependent controlled release
- Authors: Safari, Justin B , Mona, Lamine B , Sekaleli, Bafokeng T , Avudi, Bénite K , Isamura, Bienfait K , Mukubwa, Grady K , Salami, Sodeeq A , Mbinze, Jérémie K , Lobb, Kevin A , Krause, Rui W M , Nkanga, Christian I
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452727 , vital:75166 , xlink:href="https://doi.org/10.1016/j.jddst.2023.104302"
- Description: Tuberculosis, a predominantly pulmonary pathology, is currently the deadliest infection worldwide. Its treatment is based on combination therapy involving selected antimicrobials including Isoniazid. However, physicochemical properties of isoniazid negatively affect the clinical performance of current tuberculosis regimens, causing drug resistance development and increasing mortality rates. Liposomal encapsulation improves antituberculosis drug delivery; however, nano-formulation of isoniazid remains challenging due to its small molecular size and high hydrophilicity. Therefore, this study aimed to derivatize isoniazid and formulate a controlled delivery system using the concept of drug-in-cyclodextrins-in-liposomes to enhance drug biopharmaceutical properties. A prodrug of isoniazid was synthesized and screened for its ability to form stable complexes with α, β, and γ cyclodextrins. A selected inclusion complex with β-cyclodextrin was encapsulated in liposomes and assessed for controlled release of isoniazid. Successful formation of a 1:1 complex was established and characterized, followed by molecular modeling studies to demonstrate strength of the interactions within the complex and predicted complex structure. The inclusion complex was successfully encapsulated in liposomes using the thin film hydration method and the ethanol injection ultrasonic dispersion, with the latter giving the best results. These findings demonstrate the potential.
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- Date Issued: 2023
Unveiling the reactivity of truxillic and truxinic acids (TXAs): deprotonation, anion center dot center dot center dot HO, cation center dot center dot center dot O and cation center dot center dot center dot pi interactions in TXA (0) center dot center dot center dot Y+ and TXA (0) center dot center dot center dot Z (-) complexes (Y= Li, Na, K; Z= F, Cl, Br)
- Authors: Isamura, Bienfait K , Patouossa, Issofa , Muya, Jules T , Lobb, Kevin A
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452827 , vital:75173 , xlink:href="https://link.springer.com/content/pdf/10.1007/s11224-022-01965-5.pdf"
- Description: Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA0 , and Y+ (Y=Li, Na, K) and Z− (Z=F, Cl, Br) ions using M06-2X, B3LYP and 휔 B97XD functionals in conjunction with the 6–31+ +G(d,p), aug-cc-pVDZ(-X2C) and 6–311+ +G (d, p) basis sets. Our computations suggest that Y+ cations can bind to TXA0 through several combinations of cation…O and cation-π interactions, while Z− anions generally establish anion… H–O contacts. Predicted binding energies at the M06-2X/6–311+ +G(d,p) level range between−26.6 and−70.2 kcal/mol for cationic complexes and−20.4 and−62.3 kcal/mol for anionic ones. As such, TXA0 appears as an amphoteric molecule with a slight preference for electrophilic (cation... O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA0 . Anions do not behave uniformly towards TXA0 : while the fuoride anion F− induces the deprotonation of TXA0 , Br− and Cl− do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA0 …Y+ and TXA0 …Z− complexes are mainly stabilized by electrostatic and inductive efects, whose combined contributions account for more than 60 percent of the total interaction energy.
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- Date Issued: 2023
A multiscale ONIOM study of the buckminsterfullerene (C60) Diels–Alder reaction: from model design to reaction path analysis
- Authors: Isamura, Bienfait K , Lobb, Kevin A
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452517 , vital:75140 , xlink:href=" https://link.springer.com/article/10.1007/s00894-022-05319-0"
- Description: The hybrid ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) formalism is employed to investigate the Diels–Alder reaction of the buckminsterfullerene C60. Our computa-tions suggest that the ONIOM2(M06-2X/6-31G(d): SVWN/STO3G) mod-el, enclosing both the diene and the pyracyclene fragment of C60 in the higher-layer, provides a reasonable trade-of between accuracy and computational cost as it comes to predicting reaction energetics. Moreover, the frontier molecular orbital (FMO) theory and activation strain model (ASM) are jointly relied on to rationalize the efect of –OH and –CN substituents on the activation barrier of this reaction. Finally, reaction paths are scrutinized to get insight into the various forces un-derpinning the process of cycloadduct formation.
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- Date Issued: 2022
AMADAR: a python-based package for large scale prediction of Diels–Alder transition state geometries and IRC path analysis
- Authors: Isamura, Bienfait K , Lobb, Kevin A
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/453143 , vital:75226 , xlink:href="https://link.springer.com/article/10.1186/s13321-022-00618-3"
- Description: Predicting transition state geometries is one of the most challenging tasks in computational chemistry, which often requires expert-based knowledge and permanent human intervention. This short communication reports technical details and preliminary results of a python-based tool (AMADAR) designed to generate any Diels–Alder (DA) transition state geometry (TS) and analyze determined IRC paths in a (quasi-)automated fashion, given the product SMILES. Two modules of the package are devoted to performing, from IRC paths, reaction force analyses (RFA) and atomic (fragment) decompositions of the reaction force F and reaction force constant κ. The performance of the protocol has been assessed using a dataset of 2000 DA cycloadducts retrieved from the ZINC database. The sequential location of the corresponding TSs was achieved with a success rate of 95%. RFA plots confrmed the reaction force constant κ to be a good indicator of the (non)synchronicity of the associated DA reactions. Moreover, the atomic decomposition of κ allows for the rationalization of the (a)synchronicity of each DA reaction in terms of contributions stemming from pairs of interacting atoms. The source code of the AMADAR tool is available on GitHub [CMCDD/AMADAR(github. com)] and can be used directly with minor customizations, mostly regarding the local working environment of the user.
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- Date Issued: 2022
Regioselectivity, chemical bonding and physical nature of the interaction between imidazole and XAHs (X= H, F, Cl, Br, CH3, and A= S, Se, Te)
- Authors: Isamura, Bienfait K , Lobb, Kevin A , Muya, Jules T
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/453183 , vital:75229 , xlink:href="https://doi.org/10.1080/00268976.2022.2026511"
- Description: Theambidentreactivityofsmall-sizedXAHs(X=H,F,Cl,Br,CH3,andA=S,Se,Te)moleculestowardsthe imidazole molecule (IMZ) has been investigated using wave function (MP2) and Density Func-tional Theory (B3LYP, B3LYP-D3). Molecular electrostatic potentials (MEPs) and frontier molecularorbitals of monomers are computed to rationalise the regioselectivity of IMZ towards XAHs. Thechemical bonding of each complex is described in the framework of the quantum theory of atomsin molecules (QTAIM) and natural bond orbital (NBO) paradigms. The symmetry-adapted pertur-bation theory (SAPT) is employed to assess the physical nature of the interactions. Our findingssuggest that XAHs mainly bind to IMZ through H-bonding and chalcogen-bonding interactionsof weak to moderate strength, with binding energies ranging from−3.1 to−17.6 kcal/mol at theMP2/aug-cc-pVDZ(-PP) level. Topological QTAIM descriptors reveal all H-bonds between IMZ andXAHs to be purely noncovalent contacts, while chalcogen bonds of halogenated XAHs (X=F, Cl, Br) show a partial covalent character. SAPT2 calculations indicate that both H-bonded and chalcogen-bonded complexes are mainly stabilised by electrostatic interactions. Insights drawn from this studyare expected to constitute the bedrock for further investigations about noncovalent interactionbetween middle to big-sized chalcogen-containing molecules and imidazole derivatives.
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- Date Issued: 2022