Unconstrained Direct Optimization of Spacecraft Trajectories Using Many Embedded Lambert Problems

Journal of Optimization Theory and Applications - Direct optimization of many-revolution spacecraft trajectories is performed using an unconstrained formulation with many short-arc, embedded...     

A methodology to select suppliers to increase sustainability within supply chains

Central European Journal of Operations Research - Sustainability practice within supply chains remains in an early development phase. Enterprises still need tools that support the integration of...     

Persistent Monitoring by Multiple Unmanned Aerial Vehicles Using Bernstein Polynomials

Journal of Optimization Theory and Applications - A framework for monitoring a target modeled as Dubins car using multiple UAVs is proposed. The UAVs are subject to minimum and maximum speed,...     

Influence of Polarity and Activation Energy in Microwave–Assisted Organic Synthesis (MAOS)

The aim of this work was to determine the parameters that have decisive roles in microwave-assisted reactions and to develop a model, using computational chemistry, to predict a priori the type of reactions that can be improved under microwaves. For this purpose, a computational study was carried out on a variety of reactions, which have been reported to be improved under microwave irradiation. This comprises six types of reactions. The outcomes obtained in this study indicate that the most influential parameters are activation energy, enthalpy, and the polarity of all the species that participate. In addition to this, in most cases, slower reacting systems observe a much greater improvement under microwave irradiation. Furthermore, for these reactions, the presence of a polar component in the reaction (solvent, reagent, susceptor, etc.) is necessary for strong coupling with the electromagnetic radiation. We also quantified that an activation energy of 20–30 kcal mol⁻¹ and a polarity (μ) between 7–20 D of the species involved in the process is required to obtain significant improvements under microwave irradiation.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.     

Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy

Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing. Those inhibitors have been used without knowledge about the expression of P-gp by the treated tumor. Therefore the use of inhibitors of transmembrane efflux pumps in clinical settings is reconsidered as a promising strategy in the case of the respective efflux pump expression. We discovered novel symmetric inhibitors of the symmetric efflux pump MRP4 encoded by the ABCC4 gene. MRP4 is involved in many kinds of cancer with resistance to anticancer drugs. All compounds showed better activities than the best known MRP4 inhibitor MK571 in an MRP4-overexpressing cell line assay, and the activities could be related to the various substitution patterns of aromatic residues within the symmetric molecular framework. One of the best compounds was demonstrated to overcome the MRP4-mediated resistance in the cell line model to restore the anticancer drug sensitivity as a proof of concept.