Editorial [Hot Topic:Supramolecular Devices for the High-Throughput Screening of Drugs,Nutrients and Metabolites in Postgenomic Era (Part 2)(Guest Editor: Grzegorz Bazylak)]

Instrumentation-based HTS and μHTS is being improved by introducing nanolitre devices for dispensing fluids with extraordinary precision and biosensor-chip based multimode ultra-high sensitive readout protocols both of which are compatible with high density microwell and multiplate formats. A wide range of catalytic and affinity-based sensing elements together with variable fluorescence detection technologies have been implemented successfully into HTS which shifted the focus from observing macroscopic intermolecular events to the nanoscale, supramolecular and even single molecular level. In this way, HTS assays for drug discovery have developed information-rich, multiparameter readout systems for diverse molecular and supramolecular data that can include internal quality controls such as real-time feedback, self-diagnosis and adaptive supervising. These capabilities can reduce false-positive or false-negative rates caused by non-specific binding, degradation, precipitation, evaporation, poor solubility, or viscosity related sub-optimal concentration. Some of these emerging concepts and challenges for HTS are discussed in this issue of Combinatorial Chemistry & High Throughput Screening, which is Part 2 of a special issue commemorating the beginning of supramolecular chemistry in 1967. In the tutorial review by Achyuthan and Whitten opening this issue, some central principles of statistical data analysis in the development, optimization, validation and inter-laboratory comparability and traceability of nanoscale operated HTS as well as in vitro diagnostic (IVD) assays are reconsidered or even redefined. Since the availability of statistical and chemometric data analysis tools today does not always ensure knowledge of their boundaries, this tutorial should be useful to researchers in the pharmaceutical and combinatorial chemist communities. Recent trends, pitfalls and developments in the use of optical biosensors for different HTS protocols, especially for direct label free detection of reagents, beads and cells, are elaborated in the paper by Sanchez Rojas et al. These considerations are also discussed in the paper by Bertucci et al., which presents more detailed applications of optical biosensors in HTS of highly specific drug-protein interactions and determination of ADMET parameters of drug candidates. In addition, the paper by Langner et al., discusses the application of new concept of fluorescence probes and other supramolecular aggregate based biosensors for high-throughput assessment of membrane permeability coefficients and membrane adsorption of drugs and lead compounds. In the two research papers by Kruszewski et al., the binding affinities of a series of hydroxycamptothecins, anticancer drugs candidates, to human serum albumin and dimyristoylphosphatidylcholine liposomes were determined using innovative highthroughput steady-state fluorescence anisotropy measurements and factorial analysis of fluorescence excitation spectra. Similarly, Fadagar-Cosma et al. described the combinatorial synthesis and fluorescence quantum yields of a series of second generation asymmetrical meso-tetraphenylporphyrins as potential photosensitizers in photodynamic therapy. The fluorescence sensing approach was applied in the mini series of research papers by Liu et al., Wang et al., and Jin et al., for the study of molecular recognition and selective supramolecular binding processes between aliphatic oligopeptides and tryptophan-modified permethylated-β-cyclodextrins, fluoroquinolone-type antibiotic norfloxacin and p-sulfonated-calix[4]arene, and copper(II) cations and thiacalix[4]arene coated CdSe/ZnS quantum dots, respectively. These papers illustrate the impact of newly developed supramolecular materials, devices and procedures on peptidomics, proteomics, solubility enhancing drug encapsulation, and highly sensitive determination of inorganic impurities in drugs and pharmaceuticals, thus improving drug safety........