Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.     

Anti-Cancer Effects of Carnosine—A Dipeptide Molecule

Background: Carnosine is a dipeptide molecule (β-alanyl-l-histidine) with anti-inflammatory, antioxidant, anti-glycation, and chelating properties. It is used in exercise physiology as a food supplement to increase performance; however, in vitro evidence suggests that carnosine may exhibit anti-cancer properties. Methods: In this study, we investigated the effect of carnosine on breast, ovarian, colon, and leukemic cancer cell proliferation. We further examined U937 promonocytic, human myeloid leukemia cell phenotype, gene expression, and cytokine secretion to determine if these are linked to carnosine’s anti-proliferative properties. Results: Carnosine (1) inhibits breast, ovarian, colon, and leukemic cancer cell proliferation; (2) upregulates expression of pro-inflammatory molecules; (3) modulates cytokine secretion; and (4) alters U937 differentiation and phenotype. Conclusion: These effects may have implications for a role for carnosine in anti-cancer therapy.     

Redox- and protonation-state driven substrate-protein dynamics in respiratory complex I

Respiratory complex I is a key enzyme in the electron transport chains of mitochondria and bacteria. It transfers two electrons to quinone and couples this redox reaction to proton pumping to electrically charge the membrane it is embedded in. The charge and pH gradient across the membrane drives the synthesis of ATP. The redox reaction and proton pumping in complex I are separated in space and time, which raises the question of how the two reactions are coupled so efficiently. Here, we focus on the unique ～35 Å long tunnel of complex I, which houses the binding site of quinone reduction. We discuss the redox and protonation reactions that occur in this tunnel and how they influence the dynamics of protein and substrate. On the basis of recent structural data and results from molecular simulations, we review how quinone reduction and dynamics may be coupled to proton pumping in complex I.     

Understanding cathode materials in aqueous zinc–organic batteries

Organic electrode materials (OEMs) are being investigated as promising candidates for aqueous zinc-ion batteries (AZIBs) owing to their environmental friendliness, cost-effectiveness, and structural diversity, and tunability. Understanding the correlation between structural regulation of OEMs and their electrochemical property in AZIBs is vital to rational design of OEMs. Herein, we first discuss the fundamentals of the energy storage mechanism of OEMs. Then, strategies to improve the electrochemical performance, including the specific capacity, voltage, rate capability, and cycling stability, are elaborated from the perspective of molecular engineering. Finally, we share our views on the remaining challenges and prospects of OEMs in AZIBs.     

A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices

Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC–MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.     

Analyses of reaction rate data for the simple hydrolysis of acetic anhydride in the acetonitrile/water and acetone/water cosolvent systems using recently developed thermodynamic rate equations

This article presents reaction rate data for the simple hydrolysis of acetic anhydride in the acetonitrile/water and acetone/water cosolvent systems and regression analyses using recently developed thermodynamic rate equations that contain electrostatic and solvent-solute terms. The isomole fraction plots for these reaction systems are linear, and previous theoretical work has shown that the electrostatic term is negligible for such systems. On the other hand, the reaction rates are dependent upon the cosolvent mole fraction, indicating that the solvent-solute term, which is modeled empirically, is significant. The results of the analyses provide the foundation for a paradigm shift away from the emphasis on electrostatic effects to more tenable explanations of kinetic behavior in solvent systems.     

Detailed experimental and kinetic modeling study of 3-carene pyrolysis

3-Carene is an important potential biofuel with properties similar to the jet-propellant JP-10. Its thermal decomposition and combustion behavior is to date unknown, which is essential to assess its quality as a fuel. A combined experimental and kinetic modeling study has been conducted to understand the initial decomposition of 3-carene. The pyrolysis of 3-carene was investigated in a jet-stirred quartz reactor at atmospheric pressure, at temperatures varying from 650 to 1050 K, covering the complete conversion range. The decomposition of 3-carene was observed to start around 800 K, and it is almost complete at 970 K. Online gas chromatography shows that primarily aromatics are generated which suggests that 3-carene is not a good fuel candidate. The potential energy surface for the initial decomposition pathways determined by KinBot shows that a hydrogen elimination reaction dominates, giving primarily cara-2,4-diene. Next to this molecular pathway, radical pathways lead to aromatics via ring opening. The kinetic model was automatically generated with Genesys and consists of 2565 species and 9331 reactions. New quantum chemical calculations at the CBS-QB3 level of theory were needed to calculate rate coefficients and thermodynamic properties relevant for the primary decomposition of 3-carene. Both the conversion of 3-carene and the yields of the primary products (ie, benzene and hydrogen gas) are well predicted with this kinetic model. Rate of production analyses shows that the dominant pathways to convert 3-carene are hydrogen elimination reaction and radical chemistry.     

Semiclassical transition state theory/master equation kinetics of HO + CO: Performance evaluation

Previously, master equation (ME) simulations using semiclassical transition state theory (SCTST) and high-accuracy extrapolated ab initio thermochemistry (HEAT) predicted rate constants in excellent agreement with published experimental data over a wide range of pressure and temperatures ≳250 K, but the agreement was not as good at lower temperatures. Possible reasons for this reduced performance are investigated by (a) critically evaluating the published experimental data and by investigating; (b) three distinct ME treatments of angular momentum, including one that is exact at the zero- and infinite-pressure limits; (c) a hindered-rotor model for HOCO that implicitly includes the cis- and trans-conformers; (d) possible empirical adjustments of the thermochemistry; (e) possible empirical adjustments to an imaginary frequency controlling tunneling; (f) including or neglecting the prereaction complex PRC1; and (g) its possible bimolecular reactions. Improvements include better approximations to factors in SCTST and using the Hill and van Vleck treatment of angular momentum coupling. Evaluation of literature data does not reveal any specific shortcomings, but the stated uncertainties may be underestimated. All ME treatments give excellent fits to experimental data at T ≥ 250 K, but the discrepancy at T < 250 K persists. Note that each ME model requires individual empirical energy transfer parameters. Thermochemical adjustments were unable to match the experimental H/D kinetic isotope effects. Adjusting an imaginary frequency can achieve good fits, but the adjustments are unacceptably large. Whether PRC1 and its possible bimolecular reactions are included had little effect. We conclude that none of the adjustments is an improvement over the unadjusted theory. Note that only one set of experimental data exists in the regime of the discrepancy with theory, and data for DO + CO are scanty.