Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers

Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of “virtually imprinted receptors” for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems.

     

Transforming nonselective into chemoselective metal catalysts for the hydrogenation of substituted nitroaromatics

It is generally accepted that good hydrogenation noble and nonnoble metal catalysts such as Pt, Ru, or Ni are not chemoselective for hydrogenation of nitro groups in substituted aromatic molecules. We have found that it is possible to transform nonchemoselective into highly chemoselective metal catalysts by controlling the coordination of metal surface atoms while introducing a cooperative effect between the metal and a properly selected support. Thus, highly chemoselective and general hydrogenation Pt, Ru, and Ni catalysts can be prepared by generating nanosized crystals of the metals on the surface of a TiO 2 support and decorating the exposed (111) and (100) crystal faces by means of a simple catalyst activation procedure. By doing this, it has been possible to change the relative rate for hydrogenating competitive groups present in the molecule by almost 2 orders of magnitude, increasing the chemoselectivity from less than 1% to more than 95%.     

Bottom-up assembly of high density molecular nanowire cross junctions at a solid/liquid interface

A monoalkylated tetrathiafulvalene derivative forms multilayer structures at the solid-liquid interface, with high density of cross junctions, which are interesting for molecular electronic circuit self-assembly.     

Chalcogenide centred gold complexes

Chalcogenide-centred gold complexes are an important class of compounds in which a central chalcogen is surrounded by several gold atoms or gold and other metals. They have special characteristics such as unusual geometries, electron deficiency and properties such as luminescence or non-linear optical properties. The best known species are the trinuclear [E(AuPR(3))(3)](+), 'oxonium' type species, that have high synthetic applicability, not only in other chalcogen-centred species, but in many other organometallic derivatives. The aurophilic interactions play an important role in the stability, preference for a particular geometry and luminescence properties in this type of derivatives (critical review, 117 references).     

Self-assembled monolayers of electroactive polychlorotriphenylmethyl radicals on Au(111)

Two new polychlorotriphenylmethyl (PTM) derivatives bearing a thioacetate and a disulfide group have been synthesized to anchor on gold substrate. On the basis of these molecules, three strategies were followed to prepare self-assembled monolayers (SAMs) of electroactive PTMs. The resulting SAMs were fully characterized by contact angle, atomic force microscopy (AFM), and time-of-flight secondary ion mass spectroscopy (ToF-SIMS). The high coverage surface and stability of the SAMs were demonstrated by cyclic voltammetry. In addition, the electrochemical experiments proved that these SAMs are bistable since it is possible to reversibly switch between the PTM radical state to the corresponding anion. The magnetic response was investigated by electron paramagnetic resonance. We observed that when the PTM SAMs are in their radical form they confer magnetic functionality to the surface, whereas when they are in the anionic state, the surface is diamagnetic. Thus, the PTM-modified substrates are multifunctional surfaces since they combine magnetic and electroactive properties. The reported results show the high potential of these materials for the fabrication of surface molecular devices.     

Optimization of taxane binding to microtubules: binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel

The microtubule binding affinities of a series of synthetic taxanes have been measured with the aims of dissecting individual group contributions and obtaining a rationale for the design of novel compounds with the ability to overcome drug resistance. As previously observed for epothilones, the positive and negative contributions of the different substituents to the binding free energies are cumulative. By combining the most favorable substitutions we increased the binding affinity of paclitaxel 500-fold. Insight into the structural basis for this improvement was gained with molecular modeling and NMR data obtained for microtubule-bound docetaxel. Taxanes with affinities for microtubules well above their affinities for P-glycoprotein are shown not to be affected by multidrug resistance. This finding strongly indicates that optimization of the ligand-target interaction is a good strategy to overcome multidrug resistance mediated by efflux pumps.     

Evaluating the "greenness" of chemical processes and products in the pharmaceutical industry--a green metrics primer

This tutorial review presents an overview of the main metrics that have been used to test and compare the 'greenness' of processes and products, primarily in the pharmaceutical industry. The green metrics cover areas of resources, materials, processing, cleaning, life cycle assessment, renewability, amongst others. Application examples of these metrics are also presented to illustrate key points and concepts.