Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.     

Quantitative UPLC‐MS/MS analysis of chlorogenic acid derivatives in antioxidant fractionates from dandelion (Taraxacum officinale) root

While qualitative studies have identified chlorogenic acids in antioxidant extracts, particularly ethyl acetate‐derived extracts, of Taraxacum officinale, quantitative analysis of these phenolic compounds remains largely unreported for this species. In this study, bioactivity‐guided fractionation of an antioxidant crude ethyl acetate extract (DPPH = 295.481 ± 0.955 mg TE g^?1 extract) from T. officinale root resulted in a number of reverse‐phase fractions that demonstrated high antioxidant activity (DPPH = 1058.733–1312.136 mg TE g^?1 extract), stronger than that of the synthetic antioxidant Trolox^®. UPLC‐MS/MS screening of these fractions for the presence of selected mono‐ and di‐caffeoylquinic acids revealed large quantities of 1,5‐dicaffeoylquinic acid present in several fractions (853.052–907.324 μg mg^?1), respectively. Due to the antioxidant potency and high levels of 1,5‐dicaffeoylquinic acid observed in these fractions, it was concluded that specifically this chlorogenic acid derivative is a major contributor to the antioxidant efficacy of dandelion root.     

A Stimulation Method to Assess the Contractile Status of the Lumbar Extensors in a Seated Posture

The purpose of present study was to develop and evaluate methods to assess stimulation responses of the lumbar extensors, as part of a longer‐term goal of detecting fatigue during prolonged sitting. Three stimulation frequencies (2, 5, and 8 Hz) were tested in separate stages, which include 3 stimulation trains and 4 sampling blocks. Repeated measures analyses of variance were used to determine whether any significant differences in mean stimulation responses occurred with respect to stimulation frequency, sampling block, and stimulation train. Reliability of measured stimulation responses was assessed within and between sampling blocks using intraclass correlation coefficients. Stimulation frequencies significantly affected the stimulation responses and time‐to‐potentiation differed between the 3 stimulation frequencies; it was highest for 2 Hz stimulation. All 3 stimulation frequencies resulted in excellent reliability within and between sampling blocks. Use of the current protocol at 2 Hz is recommended as appropriate to measure the lumbar extensors status during prolonged sitting.     

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization

Context and objective: The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery.

Materials and methods: Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings.

Results and discussion: There was a big deviation between the T_g of the polymeric caplet from the T_g's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012–0.332?mg/mL and 0.009–0.256?mg/mL for AZT and PSS over 1–28 d.

Conclusion: The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.     

Ga-doped IZO films obtained by magnetron sputtering as transparent conductors for visible and solar applications

C-axis textured thin films of gallium-doped indium zinc oxide (GIZO) with a 2% ratio of Ga/Zn, were obtained via RF-magnetron sputtering with high transparency and electrical conductivity. A Box-Behnken response surface design was used to evaluate the effects of the deposition parameters (In₂O₃ target power, deposition time, and substrate temperature) on the chemical composition, optical, electrical, and structural properties of the GIZO films. The optical constants and the electrical properties were obtained using optical models. The GIZO stoichiometry, and therefore the In/Zn atomic ratio, affected the crystallinity, crystalline parameters, band gap, and charge carrier mobility of the GIZO films. The charge carrier density was related to the change in the crystalline parameters of the hexagonal structure and the In/Zn atomic ratio. The best electrical conductivity values (1.75?×?10³ Ω^?1 cm^?1) were obtained for GIZO films with In/Zn ratio ≥?1. Several figures of merit (FOM) defined for the visible and solar regions were comparatively used to select the optimal In/Zn atomic ratio that provided the best balance between the conductivity and the transparency. The optimal In/Zn ratio was in a range of 0.85–0.90 for the GIZO films.     

Design guidelines for titania-silica-alumina ceramics with tuned anatase to rutile transformation

Titania-based ceramics with adjustable anatase-rutile fractions were obtained by milling of anatase, quartz and corundum precursors, uniaxial pressing and firing at 1100?°C. The influence of silica and alumina, combined with milling time and compaction pressure, was studied by design of experiments. The L9 orthogonal array with a three-level noise factor was employed. Firing of pure titania at 1100?°C yielded complete anatase to rutile transformation (ART), whereas stabilized samples show that an optimum amount of 9% silica and 33% alumina reduces phase transformation to only about 5?wt% rutile. An extended correlation matrix combined with analysis of variance (ANOVA) was applied to assess the combined effects of quartz, alumina, milling time and uniaxial compressing pressure on relative density, and anatase to rutile transformation. Results show absence of ART after milling, and controlled partial conversion of anatase to rutile after firing. Very good fitting was obtained by multivariate analysis on considering first and second order terms for dependence on silica contents and interactions between silica and each of the remaining factors, including milling time. This empirical dependence could be interpreted on a sound physicochemical basis, allowing the prediction of suitable compositions and processing conditions to obtain rutile-free samples by conventional ceramic processing, and to design ceramic samples with controlled fractions of anatase and rutile.     

Investigation on external stimuli engendered magnetic ordering in polycrystalline CaCu3Ti4O12 quadruple perovskite

The consequences of high energy mechanical milling, microwave-assisted heating and rapid thermal cooling on magnetic ordering in polycrystalline CaCu₃Ti₄O₁₂ cubic perovskite have been investigated by means of X-ray powder diffractometry (300?K), dc magnetization in field – cooled and zero – field cooled modes (H = 100?Oe and 1000?Oe, T?=?5–300?K) (M – T curves) and M – H loop characteristics (T?=?5?K and 300?K, H_max = 70?kOe). The M – T curves of unmilled and 16?h milled samples show pure antiferromagnetic and weak ferromagnetic ordering, respectively, 1?h and 6?h milled samples demonstrate the coexistence of both the phases while microwave-assisted and quenched samples exhibit classic antiferromagnetic transition and a low temperature paramagnetic–like contribution with different weights, well supported by the M – H loop characteristics. The observed transformations in the magnetic ordering are attributed to the ball-milling induced stress which curtails hybridization of empty Ti-3d orbitals with Cu-3d and O-2p orbitals and secondary phase formation. Oxygen vacancies associated with bound magnetic polarons originate ferromagnetism in the milled samples while unpaired electrons inhabited at the empty sites are the cause of paramagnetic centers. The low-temperature Curie – tail in M – T curve for quenched and microwave assisted samples is attributed to Ti³⁺ cations.