Novel bexarotene esters - synthesis and spectroscopic characterization

A rapid attenuated total reflectance Fourier transform infrared (ATR‐FTIR) method was developed to simultaneously measure for vegetable oils both their oxirane oxygen content (OOC) and the change in their iodine values (IV) that occur during their epoxidation. The method uses the peak area of the epoxy functional group absorption (1497.3–1432.0 cm−1) to measure OOC and the HCabsorption associated with a carbon–carbon double bond (3017.5–3004.2 cm−1) to determine the relative changes in iodine value (ΔIV). Calibrations were developed by gravimetrically blending epoxidized canola oil (ECO) with unreacted canola oil (CO) to vary both OOC and IV. Oils including canola, camelina, and flaxseed were epoxidized, during which the OOC and ΔIV were tracked as a function of time using both the new ATR‐FTIR procedures and the standard ASTM methods. Both the OOC and ΔIV values measured by the ATR‐FTIR method correlate well to values from standard methods (R2 ≥ 0.992 and mean relative error of <3%). The FTIR procedure is simple and fast to perform and facilitates the determination of selectivity (conversion of double bonds into oxirane group) and the end‐point for the epoxidation reaction, which requires measurement of both OOC and IV.Practical applications: The ATR‐FTIR method described provides a simple, rapid, and accurate means for the measurement of OOC as well as changes in iodine value during the epoxidation of vegetable oils. This allows for the determination of the degree of conversion of lipid unsaturation into epoxides. This method can be employed by manufacturers and research laboratories to study, control, and optimize epoxidation processes.The ATR‐FTIR methods described in this paper provide a simple and rapid means of monitoring OOC and IV changes during the epoxidation of vegetable oils. These methods are calibrated against standard titrimetric procedures and have been shown to produce similar results. It is especially useful that OOC and ΔIV, the two measures that are most relevant for monitoring the progress of a triacylglycerol oil epoxidation reaction, can be obtained from a single analysis. This facilitates monitoring and optimizing epoxidation processes. If the initial IV of oil is known, the method can also be used to calculate the yield, conversion, and selectivity of the reaction, as well as a study the reaction kinetics.

Aim: This study aimed to isolate, characterize, and encapsulate a lupeol-rich fraction obtained from the hexanic extract of Coccoloba uvifera L. leaves to evaluate its potential use in nutraceutical or pharmaceutical applications. Methods: The C. uvifera leaf extract was fractionated by column chromatography and the presence of lupeol was assessed by thin layer chromatography, attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry (LC-MS). Additionally, the lupeol-rich fraction was characterized according to its antioxidant capacity and cytotoxicity. Finally, this fraction was encapsulated into electrospun nanofibers made of high degree of polymerization agave fructans (HDPAF) combined with polyethylene oxide (PEO). The obtained nanofibers were characterized in terms of morphology, chemical composition, and in vitro permeability using the Caco-2 cell line. Results: Fraction 6 showed a 77% of lupeol, quantified by chromatography, and presented a 7.3% inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH). 100 µg/mL of fraction 6 showed a decrease in Caco-2 cell viability. Finally, fraction 6 was encapsulated into electrospun nanofibers, which showed an increase in the apparent permeability of the lupeol present in fraction 6 in Caco-2 cells in comparison to neat fraction 6. Conclusions: It was possible to isolate and encapsulate a lupeol-rich fraction from C. uvifera into electrospun nanofibers, which allows the increasing the apparent permeability of lupeol, and consequently, they could be used for nutraceutical or pharmaceutical applications.

The fatty acid sensing nuclear receptor families retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs) hold therapeutic potential in neurodegeneration. Valuable pleiotropic activities of Wy14,643 in models of such conditions exceed its known PPAR agonistic profile. Here, we characterize the compound as an RXR agonist explaining the pleiotropic effects and report its systematic structure-activity relationship analysis with the discovery of specific molecular determinants driving activity on PPARs and RXRs. We have designed close analogues of the drug comprising selective and dual agonism on RXRs and PPARs that may serve as superior pharmacological tools to study the role and interplay of the nuclear receptors in various pathologies. A systematically optimized high potency RXR agonist revealed activity in vivo and active concentrations in brain. With its lack of RXR/liver X receptor-mediated side effects and superior profile compared to classical rexinoids, it establishes a new class of innovative RXR modulators to overcome key challenges in RXR targeting drug discovery.

Background: In forensic chemistry, the examination of evidence collected from explosion sites continues to be a significant field of research, driven by the growing need for enhanced homeland security in response to terrorist and warfare risks. A terrorist arranges a detonation cord to place a charge on an improvised explosive device. In India, detonating cords are widely utilized in mining. Pentaerythritol tetra nitrate (PETN) is the most exploitable high explosive used as an explosive core within the plastic covering of detonating cord. There has been significant attention given to the detection of PETN as an explosive because of concerns related to military and public safety. Objective: The rapid detection of PETN has become increasingly important in real crime samples because of its low vapor pressure and thermal liability. The main objective of the present study was to rapidly identifying PETN in crime samples (intact and defused detonating cord) of forensic laboratories using chromatography and spectroscopy methods. Methods: Spot tests, thin layer chromatography (TLC) and Attenuated total reflectance - Fourier Transform Infrared Spectroscopy (ATR-FTIR) spectroscopy methods were used to identify PETN in intact and disposed form of detonating cord. Results: PETN was been preliminarily detected in spot tests and TLC. As ATR-FTIR does not use high temperature or thermal desorption, it was used in the present study for confirmation of PETN in seized real crime samples of detonating cord in intact and disposed form. Conclusions: The integration of multiple techniques enhances detection reliability in forensic chemistry. ATR-FTIR spectroscopy proved to be an important technique without the use of other chemical/other instrumental analysis and easily classify among different samples received for the forensic opinion.

This study presents the synthesis and comprehensive characterization of tin dioxide nanoparticles (SnO2NPs). SnO2NPs were obtained using a conventional wet-chemistry route and an environmentally friendly green-chemistry approach employing plant extracts from rooibos leaves (Aspalathus linearis), pomegranate seeds (Punica granatum), and kiwifruit peels (family Actinidiaceae). The thermal stability and decomposition profiles were analyzed by thermogravimetric analysis (TGA), while their structural and physicochemical properties were investigated using X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), ultraviolet–visible (UV–Vis) spectroscopy, dynamic light scattering (DLS), Raman spectroscopy, and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Transmission electron microscopy (TEM) confirmed the nanoscale morphology and uniformity of the obtained particles. The photocatalytic activity of SnO2NPs was evaluated via the degradation of methyl orange (MeO) under UV irradiation, revealing that nanoparticles synthesized using rooibos extract exhibited the highest efficiency (68% degradation within 180 min). Furthermore, surface-enhanced Raman scattering (SERS) spectroscopy was employed to study the adsorption behavior of L-phenylalanine (L-Phe) on the SnO2NP surface. To the best of our knowledge, this is the first report demonstrating the use of pure SnO2 nanoparticles as SERS substrates for biologically active, low-symmetry molecules. The calculated enhancement factor (EF) reached up to two orders of magnitude (102), comparable to other transition metal-based nanostructures. These findings highlight the potential of SnO2NPs as multifunctional materials for biomedical and sensing applications, bridging nanotechnology and regenerative medicine.

Synthesis, spectroscopic characterization and antibacterial evaluation by chalcones derived of acetophenone isolated from Croton anisodontus Müll.Arg.

Linear and nonlinear optical parameters of biodegradable chitosan/polyvinyl alcohol/sodium montmorillonite nanocomposite films for potential optoelectronic applications

A new hyphenated technique using thin-layer chromatography (TLC) to separate analytes in mixtures, coupled with mid-infrared (MIR) laser spectroscopy for identification and quantification, is presented. The method, which provides a means for rapid screening of analytes that is practical, low-cost, fast, robust, and reproducible, was tested using nitroaromatic and aliphatic nitro high explosives (HEs) as target analytes. HEs are anthropogenic contaminants containing an -NO2 group. For validation of the new technique, a direct comparison of the 2,4,6-trinitrotoluene (TNT) spectrum, obtained by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy coupled with TLC, was carried out. The MIR laser spectroscopy-based method was evaluated by calculating the analytical figures of merit regarding the calibration curves' linearity and the method's sensitivity and precision. The TNT spectrum obtained by the MIR laser method showed two prominent and characteristic bands of the explosive at approximately 1350 cm-1 and 1550 cm-1 compared to the spectrum acquired by ATR-FTIR. The detection limit calculated for TNT was 84 ng, while the quantification limit was 252 ng. Multivariate analysis was used to evaluate the spectroscopic data to identify sources of variation and determine their relation. Partial least squares (PLS) regression analysis and PLS combined with discriminant analysis (PLS-DA) were used for quantification and classification. The new technique, TLC-QCL, is amenable to a smaller footprint with further developments in MIR laser technology, making it portable for fieldwork.

The adsorption of molecular ions from aqueous solutions onto colloidal silica is utilized across a wide range of technologies. Measurement of such interactions using attenuated total reflectance/Fourier transform infrared (ATR/FT-IR) spectroscopy presents challenges due to the instability of colloidal silica particle films on an ATR's diamond crystal internal reflection element (IRE). Here, the instability of silica is addressed by first depositing a thin film of colloidal ceria particles on the IRE to improve silica's adhesion. This enables the application of ATR/FT-IR spectroscopy to characterize the adsorption of quaternary ammonium ions, including the poly(2-(trimethylamino)ethyl methacrylate) (pTMAEM) and compounds modeling pTMAEM's side chain functional groups, tetramethylammonium (TMA) and acetylcholine (AChl) ions, on low- and high-silanol density silica films at varying pH values. Density functional theory (DFT) calculations are performed to model the TMA-silica and pTMAEM-silica complexes and predict their infrared (IR) spectra. The adsorption of TMA, AChl, and pTMAEM to silica is demonstrated by IR bands in the range of 950-1250 cm-1, which were dominated by transverse optical and longitudinal optical phonon modes. Langmuir adsorption constants based on optical phonon modes indicate that TMA is more strongly adsorbed to the low-silanol density films, whereas pTMAEM shows a stronger adsorption to silica overall, regardless of the silanol density. This suggested that both electrostatic and nonelectrostatic interactions contribute to TMA's adsorption, while the polymeric nature of pTMAEM enabled adsorption due to strong electrostatic interactions via multiple adsorption events. AChl's relatively weak adsorption to silica prevented the calculation of a Langmuir adsorption constant; however, the IR spectra suggested any adsorption was primarily due to the quaternary ammonium ion. The application of ATR/FT-IR spectroscopy in combination with DFT allowed a complete characterization of the adsorption of the quaternary ammonium ion onto ceria-supported colloidal silica, which may also be applied to other molecular ions, further characterizing and optimizing technologies employing similar materials.

Ink analysis provides a crucial function in forensic document examination for authentication, forgery detection, and ink dating. Today, black gel inks are widely used in both legal and non-legal documents, however they are difficult to analyse due to their pigment formulations, which undergo subtle chemical changes during ageing. Destructive techniques such as Thin Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC) can discriminate ink but are unsuitable for evidentiary purposes. Non-destructive Attenuated Total Reflectance-Fourier Transform infrared (ATR-FTIR) spectroscopy offers an alternative, yet spectral similarities among black gel inks necessitate advanced computational models to facilitate discrimination, classification and age prediction. In this study, predictive ageing models for black gel inks was developed by integrating ATR-FTIR spectroscopy with machine learning (ML). Thirty black gel inks from 23 brands were analysed. Ink lines made using the black gel ink samples were aged for twelve months under three different environmental conditions, and their infrared (IR) spectral data were recorded monthly over the period of 12 months. For age prediction, four classifiers namely Discriminant Analysis(DA), Support Vector Machine(SVM), k-Nearest Neighbour (kNN), and Decision Tree(DT) were trained on full mid-IR, fingerprint region, and PCA (Principal Component Analysis)-derived datasets. Performances of the classifiers were evaluated using accuracy, precision, recall, F1-score, ROC (Receiver Operating Characteristics), and Area Under the Curve (AUC). For age prediction, DA achieved the best accuracy (81.5%) with PCA features, outperforming SVM (76.1%), kNN (48.8%), and DT (40.2%). ROC-AUC values exceeded 90% across all classes. This study demonstrates that ATR-FTIR spectroscopy integrated with machine learning provides a reliable, non -destructive framework for black gel ink classification and age prediction, addressing limitations of destructive methods and strengthening forensic document analysis

(1) In this study we compared the molecular signalling elicited by rexinoids, selective retinoid X receptor (RXR)-activators, in several organs (i.e. liver, kidney, heart) and in hepatocytes of various species. (2) RXR plays the pivotal role of a hetero-dimerization partner for the members of the class II subset of nuclear receptors which regulate the transcription of numerous target genes, following chemical activation. Several of these selective activators are currently used to treat hyperlipidaemia (fibrates), type II diabetes (glitazones), or skin disorders (retinoic acid). Although these therapeutic pathways are not fully elucidated, receptor activation is considered a pre-requisite for efficacy. Therefore RXR, which accepts numerous dimeric partners, is considered a worthwhile pharmacological target. (3) We analysed a number of biochemical and molecular responses to rexinoids which were given orally to mice. Our results showed a prominent involvement of the peroxisome proliferator-activated receptor (PPARalpha) as a majority of the observed hepatic and renal regulations were abolished in PPARalpha-knockout animals. Therefore we documented the species-specificity of these rexinoid actions which were reproduced in rat primary hepatocyte cultures but not in cultures of rabbit or human origin. Conversely, we established that the regulation of the pyruvate dehydrogenase kinase (PDK4) gene in the heart, by rexinoids, is independent of PPARalpha expression. (4) Our results support the obligatory expression of the active, although quiescent, PPARalpha to sustain a subset of relevant regulations attributable to rexinoids in the liver and kidney. Their cardiac molecular signalling unveiled an alternate transduction pathway and therefore opens new prospects in the therapeutic potential of rexinoids.

The intracellular fatty acid content of insulin-sensitive target tissues determines in part their insulin sensitivity. Uptake of fatty acids into cells is a controlled process determined in part by a regulated import/export system that is controlled at least by two key groups of proteins, i.e. the fatty acid transport protein (FATP) and acyl-CoA synthetase (ACS), which facilitate, respectively, the transport of fatty acids across the cell membrane and catalyze their esterification to prevent their efflux. Previously it was shown that the expression of the FATP-1 and ACS genes was controlled by insulin and by peroxisome proliferator-activated receptor (PPAR) agonists in liver or in adipose tissue. The aim of this investigation was to determine the effects of retinoic acid derivatives on the expression of FATP-1 and ACS. In several cultured cell lines, it was shown that the expression of both the FATP-1 and ACS mRNAs was specifically induced at the transcriptional level by selective retinoid X receptor (RXR) but not by retinoic acid receptor (RAR) ligands. This effect was most pronounced in hepatoma cell lines. A similar induction of FATP-1 and ACS mRNA levels was also observed in vivo in Zucker diabetic fatty rats treated with the RXR agonist, LGD1069 (4-[1-(3,5,5,8,8-pentamethyl-5,6,7, 8-tetrahydro-2-naphthyl)ethenyl]benzoic acid). Through the use of heterodimer-selective compounds, it was demonstrated that the modulatory effect of these rexinoids on FATP-1 and ACS gene expression was mediated through activation of RXR in the context of the PPAR-RXR heterodimer. The observation that both RXR and PPAR agonists can stimulate the transcription of genes implicated in lipid metabolism, suggest that rexinoids may also act as lipid-modifying agents and support a role of the permissive PPAR-RXR heterodimer in the control of insulin sensitivity.

7234 Background: Bexarotene (Targretin) is a selective retinoid X receptor (RXR) agonist with clinical activity in NSCLC. Expression levels of RXR in NSCLC have been shown to be independent predictors of survival. The study was designed to determine the molecular activities of this compound in NSCLC and identify biomarkers of RXR activity for prognosis of survival. Methods: NSCLC cell lines and primary cultures derived from human NSCLC tumor specimens were treated with vehicle or bexarotene followed by microarray gene expression analysis. In addition, gene expression profiles were studied in NSCLC tumor samples obtained from patients treated with bexarotene (Targretin capsules) and compared with profiles in tumors and normal lung tissue from untreated patients by hierarchical clustering. Results: All cell lines and primary tumor cultures showed changes in gene expression in response to bexarotene to various degrees, indicating a universal capacity of bexarotene to elicit a molecular response in NSCLC. Genes affected play roles in cell proliferation, apoptosis, differentiation, metastasis, angiogenesis, and small molecule metabolism and transport. Some of the genes responded to bexarotene treatment in a majority or even all of the specimens, with stearoyl-CoA desaturase being the most prominently affected. When comparing NSCLC patients based on the gene expression profiles in the resected tumors, the majority of the cases separated into two distinct clusters, treated or untreated. This indicated that bexarotene may have caused relatively broad molecular changes. In addition, a set of markers identified in the in vitro experiments were also significantly overexpressed in the tumors from bexarotene-treated cases, confirming the molecular activity of the drug in the patients. Interestingly, these genes were significantly under-expressed in the untreated tumors when compared to normal lung tissue. Conclusions: These data suggest that the NSCLC tumors may exhibit reduced RXR transcriptional activity compared to normal lung tissue, which can be normalized by treatment with bexarotene, a selective RXR modulator. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand Ligand Ligand

Retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers bind to cognate response elements in vitro more efficiently than do RAR or RXR homodimers, and both RAR and RXR partners have been shown to activate various promoters in transiently transfected cells. We have now investigated whether ligand-dependent activation of both heterodimeric partners is involved in induced expression of endogenous RA-responsive genes and in P19 and F9 cell differentiation. On their own, low concentrations of retinoids selective for either RAR alpha, RAR beta, or RAR gamma did not induce or very inefficiently induced the expression of several RA target genes or triggered differentiation. An RXR-specific synthetic retinoid was similarly inefficient at any concentration. In contrast, at the same concentrations, various combinations of RAR (RAR alpha, RAR beta, or RAR gamma) and RXR selective retinoids resulted in synergistic induction of all retinoic acid (RA) target genes examined, as well as in cell differentiation. However, the magnitude of this synergistic activation varied depending on both the RAR-RXR combination and the promoter context of the responsive genes. Promiscuous activation of the three RARs, or concomitant activation of RAR alpha and RAR gamma, at selective retinoid concentrations also resulted in induction of gene expression and cell differentiation. Taken together, our results are consistent with the conclusion that the RAR and RXR partners of RAR-RXR heterodimers can synergistically activate transcription of RA-responsive genes and can induce differentiation of P19 and F9 cells. Our results also indicate that there is a significant degree of functional redundancy between the three RAR types which, however, varies with the nature of the RA target genes.

Structural studies on Demospongiae sponges from Gökçeada Island in the Northern Aegean Sea