Wide Rim Research Articles

Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions.

Proteins form native structures through folding processes, many of which proceed through intramolecular hydrophobic effect, hydrogen bond and disulfide-bond formation. In vivo, protein aggregation is prevented even in the highly condensed milieu of a cell through folding mediated by molecular chaperones and oxidative enzymes. Chemical approaches to date have not replicated such exquisite mediation. Oxidoreductases efficiently promote folding by the cooperative effects of oxidative reactivity for disulfide-bond formation in the client unfolded protein and chaperone activity to mitigate aggregation. Conventional synthetic folding promotors mimic the redox-reactivity of thiol/disulfide units but do not address client-recognition units for inhibiting aggregation. Herein, we report thiol/disulfide compounds containing client-recognition units, which act as synthetic oxidoreductase-mimics. For example, compound βCDWSH/SS bears a thiol/disulfide unit at the wide rim of β-cyclodextrin as a client recognition unit. βCDWSH/SS shows promiscuous binding to client proteins, mitigates protein aggregation, and accelerates disulfide-bond formation. In contrast, positioning a thiol/disulfide unit at the narrow rim of β-cyclodextrin promotes folding less effectively through preferential interactions at specific residues, resulting in aggregation. The combination of promiscuous client-binding and redox reactivity is effective for the design of synthetic folding promoters. βCDWSH/SS accelerates oxidative protein folding at highly condensed sub-millimolar protein concentrations.

Development of a Cone Homooxacalix[3]arene-Based Fluorescent Chemosensor for the Selective Detection of Biogenic Ammonium Ions in Protic Solvents.

We report here on the development of a fluorescent cone homooxacalix[3]arene-based receptor with a pyrene unit on the wide rim of the macrocycle (Ox3F) for the selective detection of primary ammonium ions, including those of biological importance. Ox3F was synthesized efficiently via an innovative strategy that enables the regio- and iteroselective wide rim functionalization of the readily available p-tBu-substituted homooxacalix[3]arene precursor. Nuclear magnetic resonance studies and in silico methods highlighted the endo-complexation of primary ammonium ions, including the protonated form of biogenic dopamine, tryptamine, serotonin, mexamine, and 3-iodothyronamine. The binding mode is similar for all guests with the ion deeply inserted into the polyaromatic cavity, enabling the NH3+ head to establish three hydrogen bonds with the ethereal oxygens of the macrocycle. Fluorescence quenching of the pyrene unit was observed following the π-π interaction between the pyrene moiety and the aromatic groups of serotonin, mexamine, and 3-iodothyronamine. No quenching was observed upon complexation of the smaller aromatic neurotransmitter dopamine as well as aliphatic amines and polyamines. This study presents a novel approach for biologically relevant ammonium ion chemosensing with ongoing efforts focused on translating these systems for aqueous environment applications.

Room-temperature stable Perillaldehyde—Natural cyclodextrin inclusion complexes: Preparation, characterization, thermal stability, water solubility, antioxidant activity and slow–release performance

The compound Perillaldehyde (PA) is a bioactive constituent found in natural Perilla oil, exhibiting remarkable antibacterial and antioxidant activity. However, the instability of this compound caused by the easy oxidation of its aldehyde and olefin groups imposes limitations on its extensive applications. Therefore, it is crucial to develop effective strategies for enhancing the stability of PA. This study focuses on utilizing a series of natural cyclodextrins (CDs) to synthesize inclusion complexes (ICs) with PA, aiming to improve water solubility and achieve exceptional stability at room temperature, which is essential for their potential applications in biomedicine or food industries. The hydrophobic cavity of CDs can accommodate the hexatomic ring and hydrophobic chains of PA based on the well-known size-matching effect and hydrophobic interaction, thereby forming stable ICs. Additionally, the hydrophilic outer wall of CDs imparts excellent water solubility to ICs. Phase solubility investigations demonstrate successful construction of α-CD-PA IC and β-CD-PA IC with an inclusion ratio of 1:1. Their respective stability constant (KC) are determined as 342 L/mol and 180 L/mol, indicating superior stability for α-CD-PA IC compared to β-CD-PA IC. Conversely, γ-CD with a larger cavity fails to form a stable inclusion complex with PA due to inadequate size matching. Nuclear Magnetic Resonance Hydrogen Spectroscopy (1H and 2D NMR) studies reveal that PA enters the CDs cavity (α-CD or β-CD) from its wide rim with almost the entire molecule being obliquely embedded within it. Thermogravimetry Analysis (TGA) confirm that after inclusion with CDs, PA exhibits expected stability at 25 ℃. Furthermore, CDs-PA ICs demonstrate significantly improved water solubility compared to pure PA along with enhanced antioxidant activity and slow-release performance, rendering them highly favorable for various applications.

Investigation of tyre rim protectors on the aerodynamics of a passenger vehicle

The wheels of a passenger vehicle contribute to a significant part of the vehicle’s aerodynamic drag. The previous research has shown that the flow is sensitive to small geometrical variations of the tyre, such as its shoulder profile and tread pattern. This work investigates the effect of altering the tyre profile in the transition region between the tyre and the rim by adding a so-called rim protector. Full-scale wind tunnel tests capturing forces, flow fields and surface pressures were conducted for three tyre variants in combination with two rim configurations on a crossover SUV. With a low rim protector, the forces and flow fields were similar to the reference tyre without a rim protector for both rims. With a wide, protruding, rim protector on the open rim, a larger and more outwashed front wheel wake was obtained with differences in the vortex structures, resulting in a drag penalty of 0.017CD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$0.017~C_D$$\\end{document}. The altered front wheel wake reduced the shielding of the rear wheel, resulting in differences in the rear wheel wake and base pressure. With a closed rim, the differences with the wide rim protector were much smaller with only a slight drag increase compared to the reference, demonstrating that there can be a strong interaction between the tyre and rim design.

One more step in solving the Chydorus puzzlea morphological comparison between Chydorus tilhoi Rey & Saint-Jeans, 1969 and Chydorus sphaericus (O.F. Mller, 1776) (Crustacea: Cladocera).

A number of species of Chydorus Leach, 1816 (Crustacea: Cladocera) need improvements in their taxonomy much more than any other genus within the family Chydoridae Dybowsky & Grochowski, 1894 emend. Frey, 1967, which makes the systematics of the genus still a puzzle that lacks several pieces. Here, we redescribe the African species Chydorus tilhoi Rey & Saint-Jeans, 1969 and compare its morphology with that of Chydorus sphaericus (O.F. Mller, 1776). The two taxa might be easily differentiated because C. tilhoi has a single and relatively large major head pore with a wide rim, labral keel elongated with a large spine, and postabdomen with postanal part elongated, narrowing distally and with denticles near its anal margin, organized in groups. These morphological traits are absent in C. sphaericus. Chydorus tilhoi and C. sphaericus also differ in the morphology of the first (Inner Distal Lobe setae), third (exopodite proportion), and fifth (exopodite shape) limbs. Based on the literature and our observations, the limb morphology of C. tilhoi has important similarities with that of C. breviceps, C. nitidulus and C. dentifer, and their translocation to a new genus seems to be a fundamental piece in the puzzle of Chydorus.

Thickness and design features of clinical cranial implants-what should automated methods strive to replicate?

New deep learning and statistical shape modelling approaches aim to automate the design process for patient-specific cranial implants, as highlighted by the MICCAI AutoImplant Challenges. To ensure applicability, it is important to determine if the training data used in developing these algorithms represent the geometry of implants designed for clinical use. Calavera Surgical Design provided a dataset of 206 post-craniectomy skull geometries and their clinically used implants. The MUG500+ dataset includes 29 post-craniectomy skull geometries and implants designed for automating design. For both implant and skull shapes, the inner and outer cortical surfaces were segmented, and the thickness between them was measured. For the implants, a 'rim' was defined that transitions from the repaired defect to the surrounding skull. For unilateral defect cases, skull implants were mirrored to the contra-lateral side and thickness differences were quantified. The average thickness of the clinically used implants was 6.0 ± 0.5mm, which approximates the thickness on the contra-lateral side of the skull (relative difference of -0.3 ± 1.4mm). The average thickness of the MUG500+ implants was 2.9 ± 1.0mm, significantly thinner than the intact skull thickness (relative difference of 2.9 ± 1.2mm). Rim transitions in the clinical implants (average width of 8.3 ± 3.4mm) were used to cap and create a smooth boundary with the skull. For implant modelers or manufacturers, this shape analysis quantified differences of cranial implants (thickness, rim width, surface area, and volume) to help guide future automated design algorithms. After skull completion, a thicker implant can be more versatile for cases involving muscle hollowing or thin skulls, and wider rims can smooth over the defect margins to provide more stability. For clinicians, the differing measurements and implant designs can help inform the options available for their patient specific treatment.

Development of a water-soluble ouroboros-like calix[6]arene-trisimidazole-based ligand for enhanced binding of zinc.

Increasing the thermodynamic stability of metal complexes in water is a key challenge for various applications of coordination chemistry. In this study, a calix[6]arene macrocycle functionalized with three imidazole units on the narrow rim and three primary amino legs on the wide rim was synthesized and studied. This ligand coordinates a Zn2+ cation in water, within a pH window centered around 7, through the three imidazole units and one self-included amino leg occupying the coordination site within the macrocycle cavity. The coordination process benefits from a favourable entropic effect, conferring greater thermodynamic stability to the resulting ouroboros-like complex compared to the one stabilized by an exogenous amine. Additionally, the intramolecular coordination ensures a supramolecular protection, which can be exploited for the site-selective functionalization of two out of the three amino groups. These findings demonstrate that the use of macrocyclic ligands capable of forming ouroboros-like molecular complexes represents a valuable strategy for stabilizing metal ions in water.

Calixarene-based supramolecular assembly with fluorescent gold-nanoclusters for highly selective determination of perfluorooctane sulfonic acid

The present study developed an efficient fluorescent approach, based on a supramolecular assembly between gold nanoclusters and calix[4]arene derivatives (C4A-Ds), to detect sever pollutant of perfluorooctane sulfonic acid (PFOS). For that, a series of C4A-Ds with different chain lengths and positive charges at the wider rim were designed and synthesized. Cytidine-5′ phosphate protected gold nanoclusters (AuNCs@CMP) were then assembled with calix[4]arene (LC4AP) to form AuNCs/LC4AP assembly, leading to 8-fold luminescence enhancement via the AIEE effect. However, further binding with PFOS reconstituted the as-formed assembly hrough a competitive effect, generating a fluorescence quenching. Particularly, the linear fluorescence response of AuNCs/LC4AP to PFOS realized a highly sensitive determination of the pollutant PFOS in a wide range (2.0–100 μM). In addition, the developed method successfully detected PFOS in pool water near a fire drill field, being good enough for the practical PFOS determination. The calixarene mediated method, based on the fluorescence “on–off” strategy of metal nanoclusters, is sensitive, rapid-responsive, economical, particularly, suitable for the PFOS determination in practice. It takes full advantage of the molecular recognition and self-assembly of artificial macrocyclic host molecules as a promising strategy for the PFOS determination, and will be highlight to develop new detection methods for PFOS and other poisonous compounds in environments.

Water-Soluble Pd6L3 Molecular Bowl for Separation of Phenanthrene from a Mixture of Isomeric Aromatic Hydrocarbons.

Phenanthrene is a high-value raw material in chemical industries. Separation of phenanthrene from isomeric anthracene continues to be a big challenge in the industry due to their very similar physical properties. Herein, we report the self-assembly of a water-soluble molecular bowl (TB) from a phenothiazine-based unsymmetrical terapyridyl ligand (L) and a cis-blocked 90° Pd(II) acceptor. TB featured an unusual bowl-like topology, with a wide rim diameter and a hydrophobic inner cavity fenced by the aromatic rings of the ligand. The above-mentioned features of TB allow it to bind polyaromatic hydrocarbons in its confined cavity. TB shows a higher affinity for phenanthrene over its isomer anthracene in water, which enables it to separate phenanthrene with ∼93% purity from an equimolar mixture of phenanthrene and anthracene. TB is also able to extract pyrene with around ∼90% purity from an equimolar mixture of coronene, perylene, and pyrene. Moreover, TB can be reused for several cycles without significant degradation in its performance as an extracting agent. This clean strategy of separation of phenanthrene and pyrene from a mixture of hydrophobic hydrocarbons by aqueous extraction is noteworthy.

Multiple-ion Management of Perovskites by Regulating Spatial Distribution of Hydroxyls in Oligosaccharides.

Suppressing migrations of intrinsic and extrinsic ions (e.g., Pb2+ , I- , FA+ /MA+ , and Li+ ) in organic-inorganic hybrid perovskites is critical for alleviating the hysteresis and degradation of perovskite solar cells (PSCs). However, various additives reported for that purpose usually interact with one or two types of those ions, not inhibiting multiple-ion migrations simultaneously. Two oligosaccharides (β-cyclodextrin (β-CD) and maltotetraose (G4)), containing 14 hydroxyls (-OH) with different spatial distributions, for the suppression of multiple-ion migrations in PSCs is herein employed. Compared to linear arrangement of -OH in G4, annular distribution of -OH around wide and narrow rims of β-CD can form supramolecular multi-site interactions in a focal manner with various ions, more effectively capturing and immobilizing these migrated ions. With this multiple-ion management strategy, β-CD-based PSCs exhibit an impressive efficiency of 24.22% with negligible hysteresis and excellent device stability. This work highlights the significances of multi-site interactions and molecular configuration of the additive for inhibiting multi-ion migrations in PSCs.

Inclusion complexation of surfactant with β-cyclodextrin and its effect on the mixed micellization of cationic/anionic surfactants

Inclusion complexation of surfactant with β-cyclodextrin (β-CD) is an active research topic in supramolecular chemistry. For the mixed system of β-CD and cationic/anionic surfactants, the thermodynamic and molecular dynamics (MD) simulation studies can provide valuable information about synergism between cationic and anionic surfactants and competition between inclusion complexation and mixed micellization. Experimental results indicated a synergistic effect between CTAB and SL in surface tension reduction efficiency and effectiveness, and in mixed micelle formation. The surface tension experiments indicated that for single surfactant CTAB or SL, the binding stoichiometry was β-CD:surfactant = 1:1. For the 1:1 β-CD/surfactant inclusion complexes, umbrella sampling simulation results indicated that SL bound preferentially to the wide rim of β-CD, while, CTAB had a similar probability of binding to either rim of β-CD. Both experimental and simulation results indicated that the inclusion affinity of β-CD with CTAB was significantly stronger than that of β-CD with SL. Due to the electrostatic attraction between the oppositely charged headgroups, the distance between adjacent CTA+ and L− ions was significantly shorter than that between two adjacent CTA+ (or L−) ions. It encouraged us to explore whether the 1:1:1 β-CD/CTAB/SL inclusion complex could form. The MD simulation results indicated that all four possible initial 1:1:1 conformations were unstable. The final stable inclusion complexes were in 1:1 β-CD/CTAB and 1:1 β-CD/SL forms consistent with the umbrella sampling simulation results of the single surfactant. The results suggested that the inclusion interaction becomes less competitive with mixed micellization as the composition approaches the equimolar ratio of CTAB and SL.

Modified Antia-Buch Flap Incorporating an Extended Temporal Scalp Incision.

The modified technique differs from the original Antia-Buch flap by completely detaching the root of the helix and adding a vertical incision to the temporal scalp to increase mobility of the flap. No scaphal resection is necessary. After complete elevation of the flaps, the flaps are advanced and inset toward each other followed by closure. In our practice, 10 patients have been treated with Noel et al's modification to the Antia-Buch flap. In each of these patients, acceptable reconstruction of the helical rim was able to be achieved. All the patients were pleased with their reconstructive outcome and ear anatomy was able to be successfully maintained. The modified Antia-Buch flap has shown to be an excellent method for large, helical rim defects, creating versatility by adding the temporal scalp incision. Our outcomes with Noel et al's modification to the original Antia-Buch flap support this method as a versatile technique for wide full-thickness helical rim defects.

Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations.

The complexation of β-cyclodextrin (β-CD) with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) was investigated using molecular docking and M062X/6-31G(d,p) calculations. The calculations suggested two possible complex formations of 1:1 and 2:1 host-guest molecular ratio of β-CD with CBD and THC. The preferred orientation of all complexes in this study exhibited the hydrogen bonding between hydroxy-substituted benzene ring of CBD and THC with the β-CD's secondary hydroxy groups at the wide rim. The calculated complexation energies indicate that formation of the 2:1 complexes (-83.53 to -135.36 kcal/mol) was more energetically favorable and chemically stable than the 1:1 complexes (-30.00 to -34.92 kcal/mol). However, the deformation energies of the host and the guest components in the 2:1 complexes (37.47-96.91 kcal/mol) are much higher than those in the 1:1 complexes (3.49-8.69 kcal/mol), which means the formation processes of the 2:1 complexes are more difficult due to the rigidity of the dimeric β-CDs. Therefore, the inclusion complexes of β-CD with CBD and THC are more likely to be in 1:1 host-guest ratio than in 2:1 molecular ratio. The results of this study supported the experimental results that the complexation constant of 1:1 β-CD/CBD (Ks = 300 M-1) is greater than that of 2:1 β-CDs/CBD (Kss = 0.833 M-1). Altogether, this study introduced the fitting parameters that could indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio, which are important for the assessment of the inclusion mechanisms as well as the relationships of reactants and products in chemical reactions.

Unveiling the Use of Wide Horizontal Rim Vessels (Bronze Age Northwest Iberian Peninsula)

This paper addresses a “wide horizontal rim vessel” belonging to the collection of Fundação Sousa d’Oliveira (Azores). Although its provenance and the circumstances of its discovery are currently unknown, the authors contend that this vessel should be attributed to the Iberian Northwest and, more specifically, to the Portuguese territory, in line with the highly homogenous distribution of this type of pottery. A morphological and stylistic study has been carried out establishing its singularity with regards to the decorative composition of the rim, which is without parallel amongst dozens of vessels of the same “family”. During the study of this piece, it has been possible to observe traces of soot and organic residues deposited both on its interior and exterior surfaces, which is recurrent in these vessels. The nature of these substances has never been determined in previous studies. In this article, we present and discuss the results obtained from the chromatographic analyses of the organic residue traces found on the vessel.

A computational study of the inclusion of β-cyclodextrin and nicotinic acid: DFT, DFT-D, NPA, NBO, QTAIM, and NCI-RDG studies.

Forming complexes with cyclodextrins can protect nicotinic acid (vitamin B3) from premature metabolism and enhance the solubility and stability of this drug. In this work, the formation of the inclusion complex of the neutral form of nicotinic acid and β-cyclodextrin was achieved. The complex is modeled using PM3, PM6-D4H3, and PM7, by considering two orientations of the guest: A and B, one is from wide to narrow rim, and the second is from narrow to the wide rim, respectively. The global minima positions were re-optimized using three density function methods: MN-15, B3LYP, and PW6B95-D3 with polarized Pople basis set 6-31G(d) in gas and aqueous phase. Orientation A showed the minimum complexation energy where the carboxylic functional group of nicotinic acid is located on the primary hydroxyl rim of β-cyclodextrin and the pyridine ring is totally embedded in the cavity. To further our study on the nature of complexation and the interactions of this host-guest system, different calculations were done. The reactivity indices showed that orientation A is harder than B and more electrophilic; the charge transfer occurred from the host to the guest and was confirmed by the natural population analysis (NPA). The natural bond orbitals (NBO) reveal the delocalization of orbitals between the host and the guest, quantum theory of atoms in molecules (QTAIM) analysis, and non-covalent interaction (NCI) analysis based on a reduced density gradient (RDG) give a detailed description of the nature of interactions between the host and the guest such as the hydrogen bonding and van der Waals interaction, and confirmed the stability of the complex given by the orientation A.

Zircon evolution from migmatite to crustally-derived granite: A case study of late Neoarchean migmatite in the Yishan area, western Shandong, North China Craton

Sequential changes in the texture, composition and U-Pb age of zircon from the late Neoarchean migmatites and related rocks in the Yishan area of western Shandong, eastern North China Craton, record the evolution of melt and magma from paleosome to crustally-derived granite. Zircon grains from the paleosome and metatexite have features of recrystallization, with narrow rims; those from leucosome have inherited cores and wide homogenous rims; those from diatexite preserve evidence of a complex evolution involving dissolution and growth, with the euhedral morphology of the rims, and the cross-cutting relationship between cores and rims, consistent with a magmatic origin. With the increase in melt content toward granite, the newly-grown zircon has clearer magmatic zoning and higher Th/U ratios. The low whole-rock Zr saturation temperatures (684–728 ℃) indicate that the diatexites, with abundant residual zircon, might be the product of low-temperature melting. The contemporaneous, crustally-derived granites, however, contain no or much less xenocrystic zircon and have high zircon saturation temperatures (740–868 ℃). Only at the higher temperature was sufficient partial melt produced to start the migration of magma out of the source region to form the granites. Anatectic (magmatic) zircons in diatexite commonly contain xenocrystic (residual) zircons, no matter how the magmatic system evolves further, the xenocrystic zircons in the anatectic (magmatic) zircons will still be retained. On the other hand, the crustlly-derived granites widely distributed in the area contain few residual zircons. Therefore, the crustally-derived granites widely distributed in western Shandong cannot form by further evolution of the diatexites, but require a higher degree of partial melting under higher temperature conditions. SHRIMP U-Pb zircon dating, combined with CL imaging, reveals that zircon crystals from the diatexites mostly are characterized by inherited cores with thick magmatic overgrowths, recording a regional anatectic event at ∼2.51 Ga. Residual source rock enclaves and xenocrystic zircons in the diatexites mostly have ages of ∼2.70 Ga and ∼2.53 Ga, suggesting that the diatexites were derived from Neoarchean continental crust.

The antiseptic activity of the drug, based on sodium hypochlorite in experimental and spontaneously infected wounds in animals

Sodium hypochlorite is the active ingredient in the antiseptic “Vitosept”. The pharmacological activity of the newly created drug is due to Oxygen, which is released in the active state by the decomposition of unstable hydrochloric acid into hydrochloric acid. A study of the antiseptic effect of the drug Vitosept, conducted on a model of stencil wounds in laboratory rats, found that the speed of healing and reducing the area of skin damage in animals was not inferior to the effectiveness of the comparison drug “Dioxisol-Darnytsia”. According to the obtained results, the latter's use is more appropriate in the first phase of the wound process. In contrast, the use of “Vitosept” in the second and third phases provided acceleration of the formation of mature granulation tissue. In the experimental wounds, proliferative processes were accelerated, and connective tissue was formed with the appearance of a soft scar. The efficacy of Vitosept in the treatment of spontaneously infected wounds has been studied in dogs. For three days from the beginning of treatment in dogs, the general condition improved, body temperature decreased to 38.6 ± 0.3 °C, heart rate was 74 ± 0.6 beats/min, respiratory movements 16 ± 0.4. Positive changes were also observed in the study of wounds. Significant changes in the condition of the injuries were found on the 5th day from the start of treatment. During this period, the general condition of the animals returned to normal, body temperature, heart rate, and respiration was within physiological values. In the dogs of the experimental group, Vitosept showed a slowing of the inflammatory reaction, which was manifested by a decrease in swelling and a reduction in local temperature. The pain was still partially preserved. The amount of purulent exudate decreased significantly. The surfaces of the torn and torn wounds were covered with a small amount of exudate of liquid consistency with detritus impurities, the pH of the wound medium was 6.8 ± 0.1. The surface of the cut wounds was unevenly covered with bright red granulation tissue. At the final stage of healing, both concentric scarring and planar epithelialization were observed. In most cases, in animals of the experimental group, there was concentric scarring, which ended in the formation of a relatively small scar. And only large wounds are healed by planar epithelialization, i.e., the appearance of a wide epithelial rim. In the case of infected wounds in dogs, the drug “Vitosept” compared to animals in the control group normalized morphological and biochemical parameters of blood – erythrocyte count, hemoglobin, blood protein, and its fractions aminotransferase activity in serum. There was a normalization of the values of the leukogram, which indicated the rehabilitation processes in the whole body. As a result of studying the therapeutic efficacy of Vitosept, it was found that its topical application, on average, by 3–4 days accelerated the healing process with the formation of mature granulation tissues and epithelialization in dogs with infected wounds and provided asepsis and normalization of the studied indicators in the recovery process.

Amphiphilic cyclodextrins: Dimerization and diazepam binding explored by molecular dynamics simulations

Amphiphilic cyclodextrins spontaneously aggregate to form different supramolecular assemblies with potential applications in drug release. Herein, we employ extended molecular dynamics simulations in order to characterize the structure and dynamics in explicit solvent of several amphiphilic derivatives of the β-cyclodextrin (β-CD) molecule, with aliphatic chains ester-bound to the wide rim of the hydrophobic cavity. We also study the binding properties considering a typical guest (diazepam) and the dimerization of these macrocyclic systems, assessing the relative stability of the complexes by means of end-point free energy methods. Different lengths (C4, C10, and C14 atoms) are considered for the alkyl side chains included in the amphiphilic β-CD-Cn molecules. According to the simulations, the length of these Cn moieties determines the complexing and aggregation capabilities of the β-CD-Cn systems. Compared to the native β-CD, the alkyl side chains in the β-CD-Cn molecules destabilize the inclusion complexes with diazepam and hinder the access of guest molecules to the hydrophobic cavity. In turn, dimerization is favored in the largest amphiphilic derivatives associated to the hydrophobic interaction between the Cn fragments.

Hydrolysis and Enantiodiscrimination of (R)- and (S)-Oxazepam Hemisuccinate by Methylated β-Cyclodextrins: An NMR Investigation.

Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di-O-methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri-O-methyl)-β-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative (R)- or (S)-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized β-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.

Molecular insights into complex formation between scandenin and various types of β-cyclodextrin

Atomistic molecular dynamics (MD) simulation of the inclusion complexes formation between scandenin, a phytochemical compound found in D. scandens, and five different types of cyclodextrin (CD); β-cyclodextrin (βCD), 2-hydroxypropyl βCD (2-HPβCD), 6-hydroxypropyl βCD (6-HPβCD), 2,6-dimethyl βCD (2,6-DMβCD), and 2,6-dihydroxypropyl βCD (2,6-DHPβCD) were carried out via two possible orientations of the guest molecule. The simulated results revealed that scandenin preferentially located within all the studied βCDs nanocavities by inserting its hydroxyphenyl ring and pyran terminal close to the narrow and wider rims (conf-A), respectively. In another feasible orientation (conf-B), the guest substance was deeply included into the lipophilic cavity of only 6-HPβCD and 2,6-DMβCD, but not in the other cyclodextrins. The favored inclusion formation of scandenin/2,6-DHPβCD occurred when the guest interpolated its hydroxyphenyl terminal into CD hydrophobic interior. Binding free energy calculation based on the MM-PBSA approach indicated that the modified βCDs (except for 2,6-DHPβCD) showed the stronger binding affinity to scandenin than did the parent host molecule. The results could help in selecting suitable βCD derivatives to enhance the stability of such guest molecules prior to in vitro testing.