Structure–activity relationship study of beta-carboline derivatives as haspin kinase inhibitors

Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure–activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented

Ammonium Carbamate-Based Heat Exchanger Reactor as an Endothermic Heat Sink for Thermal Management

We present our work on the investigation of a chemical reactor heat sink which used an endothermic reaction to absorb low-grade heat. Ammonium carbamate, which has an enthalpy of decomposition of ~2 MJ/kg and decomposes over a wide range of temperatures, was used as the endothermic chemical. The objective of the effort was to develop the methods and apparatus required to demonstrate endothermic cooling. Ammonium carbamate (AC) particles were suspended in propylene glycol (PG) and pumped through a heat exchanger, where it chemically reacted and decomposed as it absorbed heat from a hot fluid. Two conditions involving the reactants (AC in PG) were studied: (1) elevated decomposition temperatures occurring at near-ambient pressures and (2) near-ambient decomposition temperatures occurring at low pressures. The influences of reactant pressure, relative reactant temperature, reactant residence time, AC particle size, and AC mass flow rate on the heat absorption rate were investigated. Reaction pressure, residence time, and temperature were found to be the dominant factors

Molecular Modeling Approach to Prediction of Thermo-Mechanical Behavior of Thermoset Polymer Networks

Molecular dynamics and molecular mechanics simulations have been used to study thermo-mechanical response of highly cross-linked polymers composed of epoxy resin DGEBA and hardener DETDA. The effective cross-linking approach used in this work allowed construction of a set of stress-free molecular models with high conversion degree containing up to 35000 atoms. The generated structures were used to investigate the influence of model size, length of epoxy strands, and degree of cure on thermo-mechanical properties. The calculated densities, coefficients of thermal expansion, and glass transition temperatures of the systems are found to be in good agreement with experimental data. The computationally efficient static deformation approach we used to calculate elastic constants of the systems successfully compensated for the large scattering of the mechanical properties data due to nanoscopically small volume of simulation cells and allowed comparison of properties of similar polymeric networks having minor differences in structure or chemistry. However, some of the elastic constants obtained using this approach were found to be higher than in real macroscopic samples. This can be attributed to both finite-size effect and to the limitations of the static deformation approach to account for dynamic effects. The observed dependence of properties on system size, in this work, can be used to estimate the contribution of large-scale defects and relaxation events into macroscopic properties of the thermosetting materials

Molecular Modeling Approach to Prediction of Thermo-Mechanical Behavior of Thermoset Polymer Networks

Molecular dynamics and molecular mechanics simulations have been used to study thermo-mechanical response of highly cross-linked polymers composed of epoxy resin DGEBA and hardener DETDA. The effective cross-linking approach used in this work allowed construction of a set of stress-free molecular models with high conversion degree containing up to 35000 atoms. The generated structures were used to investigate the influence of model size, length of epoxy strands, and degree of cure on thermo-mechanical properties. The calculated densities, coefficients of thermal expansion, and glass transition temperatures of the systems are found to be in good agreement with experimental data. The computationally efficient static deformation approach we used to calculate elastic constants of the systems successfully compensated for the large scattering of the mechanical properties data due to nanoscopically small volume of simulation cells and allowed comparison of properties of similar polymeric networks having minor differences in structure or chemistry. However, some of the elastic constants obtained using this approach were found to be higher than in real macroscopic samples. This can be attributed to both finite-size effect and to the limitations of the static deformation approach to account for dynamic effects. The observed dependence of properties on system size, in this work, can be used to estimate the contribution of large-scale defects and relaxation events into macroscopic properties of the thermosetting materials

Graphite Foam Infused with Pentaglycerine for Solid-State Thermal Energy Storage

The use of a solid-state phase change material, pentaglycerine, in thermal energy storage was investigated. The motivation for exploring a thermal energy storage system that relies on a solid-state phase transition is to eliminate phase change material leakage and sealing issues. Pentaglycerine was effectively injected into graphite foam, and this combination was studied for potential use in a thermal energy storage device. Graphite foam samples that contained pentaglycerine demonstrated a storage capacity that was close to the theoretical capacity. The graphite foam infused with pentaglycerine retained 100% of its storage capacity after 59 separate thermal cycles under various conditions, with many of those cycles contiguous. It was subjected to a 28% duty cycle of applied heat flux under active cooling conditions, and the duty cycle of the sample was not adversely affected by subcooling of the pentaglycerine. The one-dimensional model developed for this study assumed a homogeneous mixture of pentaglycerine and foam which were in local thermal equilibrium with each other. The numerical results reasonably represented the effects of phase change as reflected by the temperature histories for several locations within a graphite foam–pentaglycerine sample. The current study showed that the graphite foam–pentaglycerine combination has potential for use in thermal energy storage devices

IR Characterization of Tip-Functionalized Single-Wall Carbon Nanotubes

Vibrational frequencies of functionalized groups (-COOH,-CONH2, and-COOCH3) of tip-modified singlewall carbon nanotubes are estimated using density functional theory. Both metallic (5,5) and semiconducting (10,0) nanotubes are considered with single and multiple functional groups at their tip. Several differences in frequency and intensity of the characteristic CdO band between (5,5) and (10,0) tubes are observed, which might help experimentalists to identify different tubes. For example, (5,5) tubes exhibit higher CdO frequencies than (10,0) tubes for all groups, and these bands are more intense in the latter tubes. These differences persist within a narrow range of diameter. To understand the effect of nanotubes on the spectra, fragment models containing parts of tube attached to functional groups are also studied. Such a computationally inexpensive model (compared to full tube) faithfully reproduces IR spectra and may be used for a wide range of endmodified tubes

MD Simulations of Molybdenum Disulphide (MoS2): Force-Field Parameterization and Thermal Transport Behavior

In this article, we have investigated the anisotropic nature of thermal transport in molybdenum disulphide using molecular dynamics simulations. At first, a force field has been validated with respect to crystal structure and experimental vibrational spectra of MoS2. Thereafter, non-equilibrium MD simulations have been performed in two perpendicular directions (along as well as across the basal planes) to study thermal transport behavior. At room temperature, our results show an anisotropic factor of ∼4 in the values of thermal conductivity along two studied directions, which is in good agreement with recent experiments on MoS2 thin films. However, the predicted values of thermal conductivity are about an order of magnitude higher with respect to experiments. The reasoning behind these differences has been discussed in terms of layer disorder and the large number of grain boundary interfaces in experimental thin films, which consisted of nano-crystalline MoS2 grains with a predominant parallel or perpendicular basal plane orientation. Incorporation of phonon scattering via structure disorder and boundary interfaces were identified as further directions for the model refinement