Surface Design for Immobilization of an Antimicrobial Peptide Mimic for Efficient Anti-Biofouling

Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N-substituted glycine) „peptoids“ are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP-mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne–azide „click“ coupling on amino-functionalized surfaces. Our results verified that the N- and C-terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a „volumetric“ spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti-biofouling.     

Bifunctionalized allenes. Part XXIV. Competitive electrophilic cyclization of 5-(dimethoxyphosphoryl)-alka-3,4-dienoates leading to 2,5-dihydro-1, 2-oxaphospholes and 5,6-dihydro-2H-pyranes

Abstract

We report herein a study on the competitive electrophilic cyclization of 5-(dimethoxyphosphoryl)-alka-3,4-dienoates involving 5-endo-trig and 6-endo-trig mode cyclizations. Reaction with electrophiles produces mixtures of the 2-(2-oxo-2,5-dihydro-1,2-oxaphosphol-5-yl)-alkanoates and (6-oxo-5,6-dihydro-2H-pyran-2-yl)-phosphonates by competitive electrophilic cyclization due to the participation of the neighboring phosphonate and carboxylate groups.     

Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B

A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC_50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC₅₀ 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders.     

Effect of Bulky Functional Groups on Donor and Acceptor Interactions and their Photoluminescence Properties

Material designs that use donor and acceptor units are often found in organic optoelectronic devices. Molecular level insight into the interactions between donors and acceptors are crucial for understanding how such interactions can modify the optical properties of the organic optoelectronic materials. In this paper, tris(4-(tert-butyl)phenyl)amine (pTPA) was synthesized as a donor in order to compare with unmodified triphenylamine (TPA) in a donor–acceptor system by having 2,4,6-triphenyl-1,3,5-triazine (TRZ) as an acceptor. Dimerization of donors and acceptors occurred in solvent when the concentration of solute is high. At 0 K, using a polarizable continuum model, the nitrogen atom of TPA is found to stack on top of the center of triazine of TRZ, whereas such alignment is offset in pTPA and TRZ. We attributed such alignment in TPA-TRZ as the result of attractive interactions between partial localization of 2p_z electrons at the nitrogen atom of TPA and the π deficiency of triazine in TPA-TRZ. By taking into account random motions of the solvent effect at 300 K in quantum molecular dynamics and classical molecular dynamics simulations to interpret the marked difference in emission spectra between TPA-TRZ and pTPA-TRZ, it was revealed that the attractive interaction between pTPA and TRZ in toluene is weaker than TPA and TRZ. Because of the weaker attractive interaction between pTPA and TRZ in toluene, the dimers adopted numerous ground state conformations resulting in broad emission bands superimposed with multiple small Gaussian peaks. This is in contrast to TPA-TRZ which has only one dominant dimer conformation. This study demonstrates that the strength of intermolecular interactions between donors and acceptors should be taken into consideration in designing supramolecular structures.     

Wavelet transforms in separation science for denoising and peak overlap detection

Wavelet transform is a versatile time‐frequency analysis technique, which allows localization of useful signals in time or space and separates them from noise. The detector output from any analytical instrument is mathematically equivalent to a digital image. Signals obtained in chemical separations that vary in time (e.g., high‐performance liquid chromatography) or space (e.g., planar chromatography) are amenable to wavelet analysis. This article gives an overview of wavelet analysis, and graphically explains all the relevant concepts. Continuous wavelet transform and discrete wavelet transform concepts are pictorially explained along with their chromatographic applications. An example is shown for qualitative peak overlap detection in a noisy chromatogram using continuous wavelet transform. The concept of signal decomposition, denoising, and then signal reconstruction is graphically discussed for discrete wavelet transform. All the digital filters in chromatographic instruments used today potentially broaden and distort narrow peaks. Finally, a low signal‐to‐noise ratio chromatogram is denoised using the procedure. Significant gains (>tenfold) in signal‐to‐noise ratio are shown with wavelet analysis. Peaks that were not initially visible were recovered with good accuracy. Since discrete wavelet transform denoising analysis applies to any detector used in separation science, researchers should strongly consider using wavelets for their research.     

In‐situ preparation of porous monolithic polymer inside hollow fiber as a micro‐solid phase extraction device for glucocorticoids in cosmetics

Glucocorticoids have a certain whitening effect on the skin. However, frequent and long‐term use of cosmetics including glucocorticoids is harmful to health. Herein, we proposed a novel micro‐solid phase extraction method for the detection of prednisolone acetate, prednisone, and prednisolone in cosmetics coupled with high‐performance liquid chromatography. In this method, porous monolithic polymer micro‐extraction bars were prepared by “one‐step, one‐pot” in situ photopolymerization combined with sacrificial support in hollow fiber under water atmosphere. The crucial factors such as pH of sample solution, extraction, and elution times that influence micro‐extraction were optimized and found to be 9.0, 2 h, and 32 min, respectively. Under the optimum experimental conditions, the linear range of the calibration curves were from 5.0 to 2000 µg/L with correlation coefficients (R²) between 0.9922 and 0.9996. The limit of detection and limit of quantification were 1.5 µg/L and 5.0 µg/L, respectively, and the recoveries were found to be in range of 69.0–113.3%. The analysis of precision for intraday and interday were less than 10.40 and 10.59%. The device has been successfully achieved photopolymerization under water atmosphere. The results indicated that this method is simple, accurate, and satisfactory for the pretreatment and determination of glucocorticoids in complex cosmetics samples.     

Stealth Liposomes (PEGylated) Containing an Anticancer Drug Camptothecin: In Vitro Characterization and In Vivo Pharmacokinetic and Tissue Distribution Study

Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG₅₀₀₀ were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG₂₀₀₀ (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG₅₀₀₀ were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG₂₀₀₀ and PEG₅₀₀₀ compared with conventional liposomes. The stealth liposomes prepared with PEG₅₀₀₀ showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG₂₀₀₀, with altered tissue distribution and pharmacokinetic parameters.     

Characterisation of Flavour Attributes in Egg White Protein Using HS-GC-IMS Combined with E-Nose and E-Tongue: Effect of High-Voltage Cold Plasma Treatment Time

Egg white protein (EWP) is susceptible to denaturation and coagulation when exposed to high temperatures, adversely affecting its flavour, thereby influencing consumers’ decisions. Here, we employ high-voltage cold plasma (HVCP) as a novel nonthermal technique to investigate its influence on the EWP’s flavour attributes using E-nose, E-tongue, and headspace gas-chromatography-ion-mobilisation spectrometry (HS-GC-IMS) due to their rapidness and high sensitivity in identifying flavour fingerprints in foods. The EWP was investigated at 0, 60, 120, 180, 240, and 300 s of HVCP treatment time. The results revealed that HVCP significantly influences the odour and taste attributes of the EWP across all treatments, with a more significant influence at 60 and 120 s of HVCP treatment. Principal component analyses of the E-nose and E-tongue clearly distinguish the odour and taste sensors’ responses. The HS-GC-IMS analysis identified 65 volatile compounds across the treatments. The volatile compounds’ concentrations increased as the HVCP treatment time was increased from 0 to 300 s. The significant compounds contributing to EWP characterisation include heptanal, ethylbenzene, ethanol, acetic acid, nonanal, heptacosane, 5-octadecanal, decanal, p-xylene, and octanal. Thus, this study shows that HVCP could be utilised to modify and improve the EWP flavour attributes.     

Isolation,Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Peşmen & Erik

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3′-disinapoyl-sucrose (1), 6-O-sinapoyl,3′-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3′-O-(O-methyl-feruloyl)-sucrose (3), 3′-O-(sinapoyl)-sucrose (4), 3′-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3′-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4′-di-O-methylquercetin-3-O-β-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (¹H NMR, ¹³C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.