scholarly journals Supramolecular Complexes of β-Cyclodextrin with Clomipramine and Doxepin: Effect of the Ring Substituent and Component of Drugs on Their Inclusion Topologies and Structural Flexibilities

2020 ◽  
Vol 13 (10) ◽  
pp. 278
Author(s):  
Thammarat Aree
Keyword(s):  
Side Effects ◽  
Density Functional ◽  
Dft Calculation ◽  
Drug Stability ◽  
Inclusion Complexation ◽  
Drug Carriers ◽  
Supramolecular Complexes ◽  
Drug Bioavailability ◽  
X Ray ◽  
Global Threat

Depression is a global threat. Tricyclic antidepressants (TCAs) are still efficacious in treating depression, albeit with more side effects. Cyclodextrins (CDs) with a suitable nanocavity are potential drug carriers and can enhance the drug bioavailability. Aiming for an atomistic understanding of the CD encapsulation facilitating the improvement of drug stability and the reduction of side effects, a comprehensive study series of the β-CD–TCA inclusion complexes through single crystal X-ray diffraction and density functional theory (DFT) calculation was undertaken. This work reports the supramolecular complexes of β-CD with two pivotal TCAs, clomipramine (CPM; 1) and doxepin (DXP; 2). The different inclusion topologies of the β-CD–TCA complexes were notable. X-ray analysis revealed that, in 1, the CPM B-ring (without chloro group) was entrapped in the β-CD cavity, whereas, in 2, the E-DXP A-ring and the Z-DXP B-ring were disordered in the cavity, yielding energetically favorable complexes primarily maintained by intermolecular C–H⋯π interactions, as indicated by DFT calculation. Because both wings of TCAs were similar, an alternative inclusion scenario of the A-ring was evidenced crystallographically in four other TCA complexes. The enhanced TCA thermodynamic stabilities via CD inclusion complexation helped to reduce the side effects and to increase the bioavailability. Moreover, the scrutinization of six TCAs in different lattice circumstances revealed the greater TCA structural flexibilities for their optimum pharmacological activity while binding with proteins.

scholarly journals Targeted Drug Delivery Systems for the Treatment of Glaucoma: Most Advanced Systems Review

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1742 ◽  
Author(s):  
Olga Cegielska ◽  
Paweł Sajkiewicz
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Targets ◽  
Drug Delivery Systems ◽  
Release Kinetics ◽  
Controlled Drug Release ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Drug Bioavailability

Each year, new glaucoma drug delivery systems are developed. Due to the chronic nature of the disease, it requires the inconvenient daily administration of medications. As a result of their elution from the eye surface and penetration to the bloodstream through undesired permeation routes, the bioavailability of active compounds is low, and systemic side effects occur. Despite numerous publications on glaucoma drug carriers of controlled drug release kinetics, only part of them consider drug permeation routes and, thus, carriers’ location, as an important factor affecting drug delivery. In this paper, we try to demonstrate the importance of the delivery proximal to glaucoma drug targets. The targeted delivery can significantly improve drug bioavailability, reduce side effects, and increase patients’ compliance compared to both commercial and scientifically developed formulations that can spread over the eye surface or stay in contact with conjunctival sac. We present a selection of glaucoma drug carriers intended to be placed on cornea or injected into the aqueous humor and that have been made by advanced materials using hi-tech forming methods, allowing for effective and convenient sustained antiglaucoma drug delivery.

DFT Study on Two Plausible Mechanistic Routes to Pyrazolo[3,4-d]pyrimidine-4- Amines from Pyrazoloformimidate

2020 ◽  
Vol 24 (2) ◽  
pp. 216-229
Author(s):  
Amal Al-Azmi
Keyword(s):  
Density Functional ◽  
Room Temperature ◽  
Dft Calculation ◽  
Reaction Pathways ◽  
Nucleophilic Attack ◽  
X Ray Diffraction ◽  
Dimroth Rearrangement ◽  
Functional Theory ◽  
X Ray ◽  
Moderate Yield

Pyrazolo[3,4-d]pyrimidine-4-amine was prepared at room temperature in a catalyst- free medium with moderate yield and characterized by spectroscopic and X-ray diffraction techniques. Two possible mechanistic routes were suggested for its formation. Route 1 entails attack by the N of the amine on the imidate carbon followed by Dimroth rearrangement after cyclization. Route 2 is the nucleophilic attack by the amine on the CN function followed by cyclization to pyrazolo[3,4-d]pyrimidine-4-amine. Density functional theory (DFT) calculation studies of the two proposed reaction pathways illustrated that the Route 2 reaction was more likely than that of Route 1.

scholarly journals Fluorine-Containing Dibenzoanthracene and Benzoperylene-Type Polycyclic Aromatic Hydrocarbons: Synthesis, Structure, and Basic Chemical Properties

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3337 ◽  
Author(s):  
Otohiro Gotsu ◽  
Tomomi Shiota ◽  
Hiroki Fukumoto ◽  
Tomoko Kawasaki-Takasuka ◽  
Takashi Yamazaki ◽  
...  
Keyword(s):  
Density Functional ◽  
Dft Calculation ◽  
Chemical Properties ◽  
Crystallographic Analysis ◽  
Functional Theory ◽  
X Ray ◽  
Td Dft ◽  
Polycyclic Aromatic ◽  
Stilbene Derivatives ◽  
Hydrocarbons Synthesis

Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π–π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation.

scholarly journals Synthesis, Characterization, Absorption Properties, and Electronic Structures of Paddlewheel-Type Dirhodium(II) Tetra-μ-(n-naphthoate) Complexes: An Experimental and Theoretical Study

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 447 ◽  
Author(s):  
Yusuke Kataoka ◽  
Raiki Fukumoto ◽  
Natsumi Yano ◽  
Daiki Atarashi ◽  
Hidekazu Tanaka ◽  
...  
Keyword(s):  
Electronic Structures ◽  
Density Functional ◽  
Dft Calculation ◽  
X Ray Diffraction ◽  
Absorption Properties ◽  
Thermal Stabilities ◽  
Functional Theory ◽  
X Ray ◽  
Light Region ◽  
Ligand Charge Transfer

The reactions of [Rh2(O2CCH3)4(OH2)2] with n-naphthalenecarboxylic acids (n = 1: 1-HNC, n = 2: 2-HNC) afford the dirhodium tetra-μ-(n-naphthoate) complexes [Rh2(1-NC)4] (1) and [Rh2(2-NC)4] (2), respectively. Single crystal X-ray diffraction analyses of [1(OCMe2)2] and [2(OCMe2)2], which were obtained by recrystallization from acetone (OCMe2) solutions of 1 and 2, reveal that the dirhodium cores are coordinated by four equatorially bridging naphthoate ligands and two axial OCMe2 ligands. Density functional theory (DFT) calculation confirmed that (i) the single Rh–Rh bond is formed between the two Rh ions and (ii) the electronic structures between two Rh ions in [1(OCMe2)2] and [2(OCMe2)2] are best described as π4δ2σ2δ*2π*4 and δ2π4σ2δ*2π*4, respectively. Time-dependent DFT (TDDFT) calculations clarify the absorption band characters of [1(OCMe2)2] and [2(OCMe2)2]; the former shows the bands due to d–d and metal–to–metal-ligand charge transfer (MMLCT) excitations in the visible light region, whereas the latter shows the bands due to only d–d excitations in the same region. The electrochemical properties and thermal stabilities of [1(OCMe2)2] and [2(OCMe2)2] were also investigated in this study.

scholarly journals Crystal structure of aqua(citric acid)(hydrogen citrato)calcium monohydrate, [Ca(HC6H5O7)(H3C6H5O7)(H2O)]·H2O, from synchrotron X-ray powder data, and DFT-optimized crystal structure of existing calcium hydrogen citrate trihydrate, [Ca(HC6H5O7)(H2O)3]

2020 ◽  
Vol 76 (10) ◽  
pp. 1689-1693
Author(s):  
James A. Kaduk
Keyword(s):  
Crystal Structure ◽  
Citric Acid ◽  
Density Functional ◽  
Dft Calculation ◽  
The Other ◽  
Powder Diffraction Data ◽  
Hydrogen Atoms ◽  
Acta Cryst ◽  
Coordination Polyhedra ◽  
X Ray

The crystal structure of `aquabis(dihydrogen citrato)calcium hydrate', better formulated as aqua(citric acid)(hydrogen citrato)calcium monohydrate, (I), has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. The CaO8 coordination polyhedra are isolated, but occur in layers parallel to the ab plane. Both the Rietveld-refined and DFT-optimized structures indicate that one citrate is doubly ionized and that the other is citric acid. All of the active hydrogen atoms participate in strong (11–16 kcal mol−1) hydrogen bonds. Hydrogen atoms were added to the existing calcium hydrogen citrate trihydrate structure [Sheldrick (1974). Acta Cryst. B30, 2056–2057; CSD refcode: CAHCIT], (II), and a DFT calculation was carried out to assess the hydrogen bonding and compare it to this optimized structure.

scholarly journals Inclusion Scenarios and Conformational Flexibility of the SSRI Paroxetine as Perceived from Polymorphism of β-Cyclodextrin–Paroxetine Complex

2022 ◽  
Vol 15 (1) ◽  
pp. 98
Author(s):  
Thammarat Aree
Keyword(s):  
Inclusion Complexes ◽  
Potential Energy Surfaces ◽  
Density Functional ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Global Mental Health ◽  
Inclusion Complexation ◽  
Crystal Form ◽  
Conformational Flexibility ◽  
Dispersion Interactions ◽  
Drug Bioavailability

Depression, a global mental health problem, is prevalent during the coronavirus disease 2019 (COVID-19) pandemic and can be efficiently treated by selective serotonin reuptake inhibitors (SSRIs). Our study series aims at forwarding insights on the β-cyclodextrin (β-CD)–SSRI inclusion complexes by X-ray crystallography combined with density functional theory (DFT) calculation. Here, we report a new crystal form (II) of the 1:1 β-CD–paroxetine (PXT) complex, which is inspired by the reported 2:1 β-CD–PXT complex (crystal form I), reflecting an elusive phenomenon of the polymorphism in CD inclusion complexes. The β-CD–PXT polymorphism stems from the PXT conformational flexibility, which is defined by torsion angles κ, ε around the -CH2–O- group bridging the A- and C–D-rings, of which those of PXT in I and II are totally different. While PXT (II) in an open V-shaped conformation that has the B-ring shallowly inserted in the β-CD cavity, PXT (I) in a closed U-shaped structure is mostly entirely embedded in the β-CD dimeric cavity, of which the A-ring is deeply inserted in the main β-CD cavity. However, PXT molecules in both crystal forms are similarly maintained in the CD cavity via host–guest N–H···O5/O6 H-bonds and C/O–H···π(B/C) interactions and β-CDs have similar 3D arrangements, channel (II) vs. screw-channel (I). Further theoretical explorations on the β-CD–PXT thermodynamic stabilities and the PXT conformational stabilities based on their potential energy surfaces (PESs) have been completed by DFT calculations. The 2:1 β-CD–PXT complex with the greater presence of dispersion interactions is more energetically favorable than the unimolar complex. Conversely, whereas free PXT, PXT (II) and PXT in complex with serotonin transporter are more energetically stable, PXT (I) is least stable and stabilized in the β-CD cavity. As SSRIs could lessen the COVID-19 severity, the CD inclusion complexation not only helps to improve the drug bioavailability, but also promotes the use of antidepressants and COVID-19 medicines concurrently.

Cu Doped TiO2: Visible Light Assisted Photocatalytic Antimicrobial Activity and High Temperature Anatase Stability

2018 ◽  
Author(s):  
Snehamol Mathew ◽  
Priyanka Ganguly ◽  
Stephen Rhatigan ◽  
Vignesh Kumaravel ◽  
Ciara Byrne ◽  
...  
Keyword(s):  
Visible Light ◽  
Visible Light Irradiation ◽  
Density Functional ◽  
Anatase Phase ◽  
Sol Gel ◽  
Chemical Properties ◽  
Light Irradiation ◽  
Health Concern ◽  
Bacterial Inactivation ◽  
X Ray

Indoor surface contamination by microbes is a major public health concern. A damp environment is one potential sources for microbe proliferation. Smart photocatalytic coatings on building surfaces using semiconductors like titania (TiO<sub>2</sub>) can effectively curb this growing threat.<b> </b>Metal-doped titania in anatase phase has been proved as a promising candidate for energy and environmental applications. In this present work, the antimicrobial efficacy of copper (Cu) doped TiO<sub>2 </sub>(Cu-TiO<sub>2</sub>) was evaluated against <i>Escherichia coli</i> (Gram-negative) and <i>Staphylococcus aureus</i> (Gram-positive) under visible light irradiation. Doping of a minute fraction of Cu (0.5 mol %) in TiO<sub>2 </sub>was carried out <i>via</i> sol-gel technique. Cu-TiO<sub>2</sub> further calcined at various temperatures (in the range of 500 °C – 700 °C) to evaluate the thermal stability of TiO<sub>2</sub> anatase phase. The physico-chemical properties of the samples were characterised through X-ray diffraction (XRD), Raman spectroscopy, X-ray photo-electron spectroscopy (XPS) and UV-visible spectroscopy techniques. XRD results revealed that the anatase phase of TiO<sub>2</sub> was maintained well, up to 650 °C, by the Cu dopant. UV-DRS results suggested that the visible light absorption property of Cu-TiO<sub>2 </sub>was enhanced and the band gap is reduced to 2.8 eV. Density functional theory (DFT) studies emphasises the introduction of Cu<sup>+</sup> and Cu<sup>2+</sup> ions by replacing Ti<sup>4+</sup> ions in the TiO<sub>2</sub> lattice, creating oxygen vacancies. These further promoted the photocatalytic efficiency. A significantly high bacterial inactivation (99.9%) was attained in 30 mins of visible light irradiation by Cu-TiO<sub>2</sub>.

Highly Electron-Deficient Pyridinium-Nitrones for Rapid and Tunable Inverse-Electron-Demand Strain-Promoted Alkyne-Nitrone Cycloaddition to Bicyclo[6.1.0]nonyne

2019 ◽  
Author(s):  
Praveen Gunawardene ◽  
Wilson Luo ◽  
Alexander M. Polgar ◽  
John F. Corrigan ◽  
Mark Workentin
Keyword(s):  
Density Functional Theory ◽  
Reaction Kinetics ◽  
Density Functional ◽  
Functional Theory ◽  
X Ray ◽  
Inverse Electron Demand ◽  
X Ray Crystallography ◽  
Electron Demand

<div> <div> <p>Highly accelerated inverse-electron-demand strain-promoted alkyne-nitrone cycloaddition (IED SPANC) between a sta- ble cyclooctyne (bicyclo[6.1.0]nonyne (BCN)) and nitrones delocalized into a Cα-pyridinium functionality is reported, with the most electron-deficient “pyridinium-nitrone” displaying among the most rapid cycloadditions to BCN that is currently reported. Density functional theory (DFT) and X-ray crystallography are explored to rationalize the effects of N- and Cα-substituent modifications at the nitrone on IED SPANC reaction kinetics and the overall rapid reactivity of pyridinium-delocalized nitrones.</p> </div> </div>

Small Molecular Gemcitabine Prodrugs for Cancer Therapy

2020 ◽  
Vol 27 (33) ◽  
pp. 5562-5582 ◽  
Author(s):  
He Miao ◽  
Xuehong Chen ◽  
Yepeng Luan
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drug ◽  
Drug Stability ◽  
Effective Means ◽  
Active Form ◽  
Deoxycytidine Kinase ◽  
High Efficacy ◽  
Pyrimidine Nucleoside ◽  
Design And Synthesis

Gemcitabine as a pyrimidine nucleoside analog anticancer drug has high efficacy for a broad spectrum of solid tumors. Gemcitabine is activated within tumor cells by sequential phosphorylation carried out by deoxycytidine kinase to mono-, di-, and triphosphate nucleotides with the last one as the active form. But the instability, drug resistance and toxicity severely limited its utilization in clinics. In the field of medicinal chemistry, prodrugs have proven to be a very effective means for elevating drug stability and decrease undesirable side effects including the nucleoside anticancer drug such as gemcitabine. Many works have been accomplished in design and synthesis of gemcitabine prodrugs, majority of which were summarized in this review.

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