Effect of protonation state and N-acetylation of chitosan on its interaction with xanthan gum: a molecular dynamics simulation study

Hydrophilic matrices composed of chitosan (CS) and xanthan gum (XG) complexes are of pharmaceutical interest in relation to drug delivery due to their ability to control the release of active ingredients. Molecular dynamics simulations (MDs) have been performed in order to obtain information pertaining to the effect of the state of protonation and degree of N-acetylation (DA) on the molecular conformation of chitosan and its ability to interact with xanthan gum in aqueous solutions. The conformational flexibility of CS was found to be highly dependent on its state of protonation. Upon complexation with XG, a substantial restriction in free rotation around the glycosidic bond was noticed in protonated CS dimers regardless of their DA, whereas deprotonated molecules preserved their free mobility. Calculated values for the free energy of binding between CS and XG revealed the dominant contribution of electrostatic forces on the formation of complexes and that the most stable complexes were formed when CS was at least half-protonated and the DA was ≤50%. The results obtained provide an insight into the main factors governing the interaction between CS and XG, such that they can be manipulated accordingly to produce complexes with the desired controlled-release effect

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Molecular recognition of tripeptides containing tryptophan by cucurbit[8]uril: A computational study

In this work, molecular dynamics (MD) simulations and time-dependent density functional theory (TD-DFT) calculations were applied to study the formation of binary and ternary complexes between cucurbit[8]uril (CB8) and three tryptophan-containing tripeptides (WGG, GWG, and GGW), as well as heteroternary complexes of the tripeptides in the presence of methyl viologen (MV) as an auxiliary ligand. All complexes were stable in water, and exhibited encapsulation of the indole moiety of W. Analysis of the MD trajectories of the homoternary complexes revealed π-π stacking within the CB8 cavity between the indole rings. MM-PBSA analysis indicated higher binding energy for tripeptides containing W residue at the N-terminus. The heteroternary complexes showed two binding modes, one with MV fully included (and π-π stacked with the indole ring) and the other with MV mostly excluded. The computed UV–Visible spectra of the free guests and their heteroternary complexes exhibited new bands emerged in the spectra of the complexes, which resulted from the transitions from HOMO and HOMO–1 to LUMO related to W–MV charge transfer (CT) complexes

Synthesis, biological evaluation, and computational studies of N-benzyl pyridinium–curcumin derivatives as potent AChE inhibitors with antioxidant activity

AbstractA library of N-benzylpyridinium-based compounds, 7a-j and 8a-j, was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An in vitro assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl (8a) and fluoro (8b) derivatives were the most active, with IC50 values ≤56 nM. Compound 7f, which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC50 value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC50 = 30 ± 0.2 nM) and donepezil (IC50 = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives (7f, 7 g, 8f, and 8 g) exhibited superior AChE inhibitory activity, with Ki values of 6–16 nM, which were potent in the same range as the approved drug, donepezil. These compounds showed moderate antioxidant activities, as indicated by the results of the ABTS assay

Synthesis and characterization of ruthenium(II) azoimine-diphosphine mixed-ligand complexes

A novel family of the general type cis-[RuII(dppe)LCl2] {L = C6H5N{double bond, long}NC(COCH3){double bond, long}NAr, Ar = 2,4,6-trimethylphenyl (L1), 2,5-dimethylphenyl (L2), 4-tolyl (L3), phenyl (L4), 4-methoxyphenyl (L5), 4-chlorophenyl (L6), 4-nitrophenyl (L7), 2,5-dichlorophenyl (L8); dppe = Ph2P(CH2)2PPh2} has been synthesized. These complexes have been characterized through analytical, spectroscopic (IR, UV-Vis, and NMR) and electrochemical (cyclic voltammetry) techniques. In addition, complex 4 (where L = L4) has been further characterized by X-ray diffraction analysis. Crystallographic, electrochemical and electronic spectral data are all consistent with the azomethine ligands possessing strong π-acceptor properties. These π-acceptor properties can be "tuned" by a judicious choice of substituent on the azomethine ligand

Solvent Bar Microextraction Method Based on a Natural Deep Eutectic Solvent and Multivariate Optimization for Determination of Steroid Hormones in Urine and Water

Steroid hormones may pose potential risks to both human health and wildlife, primarily through the consumption of medication or polluted food and water; efforts are being made to monitor their levels in the human body and regulate and minimize their releases to the environment. In this study, a simple and environmentally friendly sample preparation method was developed to simultaneously determine three steroid hormones in urine and water samples. A monoterpene (menthol) and a fatty acid (lauric acid) were combined in various ratios to form a hydrophobic deep eutectic (HDE) solvent as an extraction solvent in solvent bar microextraction (SBME). Using a univariate strategy, a menthol-to-lauric acid HDE ratio of 4:1 and a pH 7 of the sample solution resulted in the highest extraction efficiency (EE%) of the selected steroids. The computational methods have been employed to predict a 4:1 HDE interaction with chosen steroids. Additionally, chemometric approaches suggested that the optimal extraction conditions involved HDEs as extract solvent confined within three SBME devices directly immersed into a 20 mL sample solution with a 30 min extraction time, followed by ultrasonication within 200 μL of elution solvent for a 5 min elution time. Under optimized conditions, the method calibration graph for the spiked selected steroids in the water and urine samples showed good linearity with R2 ≥ 0.994 with limits of detection/quantification lower than 0.40/1.35 μg L−1 and repeatability/reproducibility (RSD%, n = 5) lower than 5.09/7.11. The developed method allows a safe, rapid, and reliable analysis of three steroid hormones in human urine and water samples without using toxic volatile organic solvents

Molecular dynamics simulation study of the structural features and inclusion capacities of cucurbit[6]uril derivatives in aqueous solutions

<div><p>Molecular dynamics (MD) simulations were performed for cucurbit[6]uril (CB6) methyl and cyclohexyl derivatives in aqueous solutions. Furthermore, MD simulations have been conducted to study the inclusion complexes between each CB6 derivative with α,ω-pentane diammonium ion (NH₃⁺(CH₂)₅NH₃⁺) to estimate the binding free energies, the complex geometries and the intermolecular forces responsible for complex formation. Results show a complete inclusion of the guest molecule in the cavity of the host for all complexes. Results also indicate that the guest dynamics inside the cavity of the substituted host is similar to that for the unsubstituted host. This demonstrates that the molecular recognition of the host is not affected by the alkyl substitution at the equator. Also, there is an insignificant conformational change of the macrocyclic structure upon inclusion of the guest. Molecular mechanics/Poisson Boltzmann surface area method was used to estimate the binding free energy of each complex. Results indicate that host–guest electrostatic interactions make the largest contribution to the complex binding free energy. Moreover, van der Waals interactions add significantly to the complex stability. The guest molecules show more or less similar binding free energies with the substituted CB6 that exhibits slightly more negative values than unsubstituted CB6 which is proved also by umbrella sampling.</p></div