Transient states in [2 + 2] photodimerization of cinnamic acid: correlation of solid-state NMR and X-ray analysis

13C-CPMAS and other solid-state NMR methods have been applied to monitor the solid-state reactions of trans-cinnamic acid derivatives, which are the pioneer and model compounds in the field of topochemistry previously studied by X-ray diffraction, AFM, and vibrational spectroscopy. Single-crystal X-ray analyses of photoirradiated alpha-trans-cinnamic acid where the monomers are arranged in a head-to-tail manner have revealed the formation of a centrosymmetric alpha-truxillic acid photodimer. For a centrosymmetric dimer, however, two cyclobutane carbon signals and one carbonyl carbon signal were expected apart from other aromatic carbon signals. Instead, four cyclobutane and two carbonyl carbon signals were observed suggesting the formation of a non-centrosymmetric photodimer. Removing hydrogen bonds from the system by esterfication of alpha-truxillic acid yield a centrosymmetric photodimer. Careful analysis of the obtained products via solid-state NMR clearly showed that the observed peak splittings in the 13C-CPMAS spectra did not originate from packing effects but rather result from asymmetric hydrogen bonds distorting the local symmetry. Further evidence of this rather dynamic hydrogen-bonding stems from high-temperature X-ray data revealing that only the joint approach of both X-ray analysis and solid-state NMR at similar temperatures allows for the successful characterization of dynamic processes occurring in topochemical reactions, thus, providing detailed insight into the reaction mechanism of organic solid-state transformations.     

Phytochemical Profiling,In Vitro Biological Activities,and In Silico Molecular Docking Studies of Dracaena reflexa

Dracaena reflexa, a traditionally significant medicinal plant, has not been extensively explored before for its phytochemical and biological potential. The present study was conducted to evaluate the bioactive phytochemicals and in vitro biological activities of D. reflexa, and perform in silico molecular docking validation of D. reflexa. The bioactive phytochemicals were assessed by preliminary phytochemical testing, total bioactive contents, and GC-MS analysis. For biological evaluation, the antioxidant (DPPH, ABTS, CUPRAC, and ABTS), antibacterial, thrombolytic, and enzyme inhibition (tyrosinase and cholinesterase enzymes) potential were determined. The highest level of total phenolic contents (92.72 ± 0.79 mg GAE/g extract) was found in the n-butanol fraction while the maximum total flavonoid content (110 ± 0.83 mg QE/g extract) was observed in methanolic extract. The results showed that n-butanol fraction exhibited very significant tyrosinase inhibition activity (73.46 ± 0.80) and acetylcholinesterase inhibition activity (64.06 ± 2.65%) as compared to other fractions and comparable to the standard compounds (kojic acid and galantamine). The methanolic extract was considered to have moderate butyrylcholinesterase inhibition activity (50.97 ± 063) as compared to the standard compound galantamine (53.671 ± 0.97%). The GC-MS analysis of the n-hexane fraction resulted in the tentative identification of 120 bioactive phytochemicals. Furthermore, the major compounds as identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between the ligands and the enzymes (tyrosinase, acetylcholinesterase, and butyrylcholinesterase enzymes). The results of this study suggest that Dracaena reflexa has unquestionable pharmaceutical importance and it should be further explored for the isolation of secondary metabolites that can be employed for the treatment of different diseases.     

Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies

Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.     

Molecular selectivity and immiscibility during the crystallization of mixtures of a set of homologous self-assembling molecules

Utilizing self-assembly to create supramolecular structures is an active area at this time. Hybrid materials created by blending or doping, e.g., organic/inorganic or donor/acceptor complexes are of great interest in the design of novel materials systems. The effect of mixing of any two self-assembling molecules to modify the properties and to understand if the process of blending changes the nature of the self-assembly would be of interest. We discuss here the effect of blending of two (hydrogen bond mediated) self-assembling homologous molecules on the structure and morphology. Materials that are candidate vehicles for phase-change inkjet technology, biscarbamates with alkyl side chains, are chosen for this study. Thermal analysis and IR spectra indicate that, when two biscarbamates differing only in the length of the alkyl chain are blended, the two components are immiscible, although they are chemically similar. There is no intercalation of the alkyl chains and cocrystallization. They are thus an example of a self-sorting system. The extent of hydrogen bonding and the packing of the alkyl chains are not affected. However, each serve as a nucleating agent and reduce the size of the spherulites and crystallinity. The spherulitic growth rate decreases upon blending. Partial melting experiments show that the spherulites of each component do not form independently, but are intermixed, implying that one acts as the nucleating sites for the other. Thus, although these are self-sorting, the components in the mixture affect the morphology of each other upon crystallization. The behavior of this small molecule mixture is compared with those of hydrogen-bonded polymer blends. Studies of this nature on blends of self-assembling molecules are expected to be important in materials design for optimizing properties.     

Approaches to open fullerenes: synthesis and thermal stability of cis-1 bis(isobenzofuran) Diels-Alder adducts of C60

In a quest to form wider openings within the cage of the fullerene C60 through controlled bond-breaking reactions, we have examined the double saturation of adjacent C=C bonds within a six-membered ring of C60. We have investigated the double Diels-Alder cycloaddition of two tethered isobenzofurans to the fullerene C60. We obtained cis-1 adducts in good yields after reacting the methylene- or quinoxaline-tethered bis(isobenzofuran) precursors 2a-k with parent 3,6-dihydro-1,2,4,5-tetrazine (3b). The X-ray structure of the methylene-tethered bis(isobenzofuran)-C60 adduct 4b has been obtained; four-eclipsed substituents are held rigidly by the bicyclic addends. The cis-1 bis(isobenzofuran) bisadducts 4b and 4e-j are kinetically far more stable toward thermal retro-Diels-Alder fragmentation than are mono(isobenzofuran) adducts of C60, in solution and in the solid state as determined by 1H NMR spectroscopy or thermogravimetric analysis. A methodology for the reversible solubilization of other fullerene derivatives based on this work is also presented.     

Hetarylpyrazoles. II. Reactions of pyrazol-l'-ylpyridines

Pyrazol-l'-ylpyridines undergo electrophilic substitution reactions (bromination, chlorination, and nitration) preferentially in the pyrazole ring. There is some evidence of the mutual influence of the pyrazole and the pyridine ring on the reactivity of the system. Some modifications of the substituents were also carried out. A dihydro derivative of a new ring system, pyrazolo[1′,2′-a]pyrido[2,1-c][l,2,4]triazine was also obtained.     

Optimization and Validation of RP-LC/UV–VIS Detection Method for Simultaneous Determination of Fat-Soluble Anti-Oxidant Vitamins, all-trans-Retinol and α-Tocopherol in Human Serum: Effect of Experimental Parameters

A versatile isocratic reversed-phase liquid chromatographic/ultraviolet–visible detection method for simultaneous determination of all-trans-retinol and α-tocopherol in human serum was developed and validated after optimization of various chromatographic conditions and other experimental parameters. Analytes were separated on a Kromasil 100 RP₁₈ (150 × 4.6 mm, 5 μm) analytical column protected by a Perkin Elmer RP₁₈ (30 × 4.6 mm, 10 μm) guard cartridge. The mobile phase, methanol–water (96:04 v/v) was pumped at a flow rate of 2.2 mL min^?1 and the column eluents were monitored at the wavelength of 292 nm using retinyl acetate (1.0 μg mL^?1) as the internal standard for both analytes. Sample preparation was based on protein precipitation and stabilization with 2,6-bis(1,1-dimethylethyl)-4-methylphenol/ethanol and a two step extraction process using n-hexane followed by dichloromethane as extraction solvents. Sample size was kept 20 μL and separation of analytes was achieved in less than 7 min. The present method demonstrated acceptable values for specificity/selectivity, linearity within the expected concentration range, recovery, precision, sensitivity, stability of solutions, robustness, and system suitability specifications and tests. The method was used for monitoring all-trans-retinol and α-tocopherol concentrations in human serum samples and could also be applied to other sample matrices such as brain slices and cosmetic products if attention is paid to the extraction procedure.     

Gold nano-popcorn-based targeted diagnosis, nanotherapy treatment, and in situ monitoring of photothermal therapy response of prostate cancer cells using surface-enhanced Raman spectroscopy

Prostate cancer is the second leading cause of cancer-related death among the American male population, and the cost of treating prostate cancer patients is about $10 billion/year in the United States. Current treatments are mostly ineffective against advanced-stage prostate cancer and are often associated with severe side effects. Driven by these factors, we report a multifunctional, nanotechnology-driven, gold nano-popcorn-based surface-enhanced Raman scattering (SERS) assay for targeted sensing, nanotherapy treatment, and in situ monitoring of photothermal nanotherapy response during the therapy process. Our experimental data show that, in the presence of LNCaP human prostate cancer cells, multifunctional popcorn-shaped gold nanoparticles form several hot spots and provide a significant enhancement of the Raman signal intensity by several orders of magnitude (2.5 × 10(9)). As a result, it can recognize human prostate cancer cells at the 50-cells level. Our results indicate that the localized heating that occurs during near-infrared irradiation can cause irreparable cellular damage to the prostate cancer cells. Our in situ time-dependent results demonstrate for the first time that, by monitoring SERS intensity changes, one can monitor photothermal nanotherapy response during the therapy process. Possible mechanisms and operating principles of our SERS assay are discussed. Ultimately, this nanotechnology-driven assay could have enormous potential applications in rapid, on-site targeted sensing, nanotherapy treatment, and monitoring of the nanotherapy process, which are critical to providing effective treatment of cancer.     

The role of C-H and C-C stretching modes in the intrinsic non-radiative decay of triplet states in a Pt-containing conjugated phenylene ethynylene

The intrinsic non-radiative decay (internal conversion) from the triplet excited state in phosphorescent dyes can be described by a multi-phonon emission process. Since non-radiative decay of triplet excitons can be a significant process in organic light-emitting diodes, a detailed understanding of this decay mechanism is important if the overall device efficiency is to be controlled. We compare a deuterated Pt(II)-containing phenylene ethynylene with its non-deuterated counterpart in order to investigate which phonon modes control to the non-radiative decay path. We observe that deuteration does not decrease the non-radiative decay rate. A Franck-Condon analysis of the phosphorescence spectra shows that the electronic excitation is coupled strongly to the breathing mode of the phenyl ring and the C≡C carbon stretching modes, while high-energy C-H or C-D stretching modes play an insignificant role. We, therefore, associate the internal conversion process with the carbon-carbon stretching vibrations.     

Prolongation of the active lifetime of a biomolecular motor for in vitro motility assay by using an inert atmosphere

Over the last few decades, the in vitro motility assay has been performed to probe the biophysical and chemo-mechanical properties as well as the self-organization process of biomolecular motor systems such as actin-myosin and microtubule-kinesin. However, aggression of the reactive oxygen species (ROS) and concomitant termination of the activity of biomolecular motors during investigation remains a drawback of this assay. Despite enzymatic protection that makes use of a combination of glucose, glucose oxidase, and catalase, the active lifetime of biomolecular motors is found to be only a few hours and this short lifetime restricts further study on those systems. We have solved this problem by using a newly developed system of the in vitro motility assay that is conducted in an inert nitrogen gas atmosphere free of ROS. Using microtubule-kinesin as a model system we have shown that our system has prolonged the active lifetime of the biomolecular motor until several days and even a week by protecting it from oxidative damage.