Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads

Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.     

High‐Throughput Fabrication,Performance Testing,and Characterization of One‐Dimensional Libraries of Polymeric Compositions

A new general approach for rapid performance‐screening of polymer compositions is provided. Multiple compositions are generated as one‐dimensional libraries in a microextruder with step‐ or gradient‐composition changes in 2–10 g of polymer in < 1 min. To accelerate testing, environmental stress is applied to only local regions, followed by high‐sensitivity spatially resolved characterization. We applied our methodology for weathering of arrays of polymeric compositions and provided ranking of polymer/UV absorber compositions equivalent to traditional weathering data while achieved 20 times faster.

Sampling and measurement strategies for HT analysis of combinatorial 1D polymeric libraries: (1) spectroscopic monitoring of chemical properties, (2) in‐situ monitoring of mass and viscoelastic properties, (3) scanning spectroscopic analysis, and (4) spectroscopic imaging of a coiled polymeric array.     

Use of chemiluminescence to the study of photostability of automotive coatings

Chemiluminescence (CL) imaging has been used to study the photodegradation of two automotive coatings, a melamine-crosslinked acrylic resin and an acrylic Polyurethane, as a function of artificial weathering time. Characteristics of the CL emission from coatings, the influence of light stabilizers and different types of sample were studied. The results indicate that the method is highly sensitive and can be used to measure photodegradation in unstabilized and stabilized coatings after only 48 h and 100–200 h of exposure, respectively. Measurements can be carried out on free clearcoats or on clearcoats applied on metallic panels. It is also possible to assess the degradation of individual layers in multiple-layer coating systems. Extrapolation to the failure time of coatings by CL is not yet achievable, but results show that the technique is useful for rapidly screening the relative performance of new coating formulations or light stabilizers added to clearcoats.     

Long-Term Protection of the Last Judgment Mosaic in Prague

A sol-gel coating was used in the long-term protection of the 14th Century mosaic situated above the gates of St. Vitus cathedral, in the center of Prague Castle. The choice of a sol-gel coating is the result of a research effort involving both on-site testing in Prague and accelerated ageing of various polymers and sol-gel materials in the laboratory. The coating selected for treatment of the entire 13 m × 10 m mosaic is a multi-layer system in which an organic-inorganic sol-gel layer is placed between the glass substrate and a fluoropolymer coating. This coating combination performed very well in an accelerated weathering chamber as well as during onsite testing. Since the top layer is scheduled to be removed and re-applied periodically, it is hoped that this concept will allow long term protection to the largest outdoors mosaic north of the Alps. On-site application of the coatings on the entire mosaic started in 1998 and will be completed in 2000.     

Development of Anti-Reflection (AR) Coating on Plastic Panels for Display Applications

Traditionally, various vacuum-based processes have been used for producing interference-type anti-reflection (AR) coatings on large area substrates for different commercial applications. In this paper, the development of sol-gel derived AR coating on large plastic substrates for display application is presented. The sol-gel dip coating process was used to deposit thin films on large size plastic panels. By developing sols with different refractive indices, multi-layer thin-film AR coating stacks were designed and fabricated. These coatings possess good uniformity and meet stringent automotive specifications. This technology has been commercialized successfully for dashboard instrument panel application in Toyota's new hybrid engine car, named Prius.In this paper, AR coatings prepared by the sol-gel process are reviewed. The basic design concept for an AR coating, the coating preparation procedure, and important parameters of the solution coating process are discussed. Optical constants of the coating materials were characterized by using spectroscopic ellipsometry. Optical, mechanical and environmental tests were performed on the sol-gel derived AR coating stack. The sol-gel derived AR coating possesses equivalent or superior properties when compared to the major commercially available AR coating products.     

Combinatorial materials research applied to the development of new surface coatings I: a multiwell plate screening method for the high-throughput assessment of bacterial biofilm retention on surfaces

Combinatorial, high-throughput capabilities have been established to aid in the rapid development of new and effective antifouling marine coatings for naval applications. A biological screening process involving marine bacteria was developed that allows for rapid and effective quantification of bacterial biofilm growth and retention on large numbers of coating surfaces in parallel. The screening process involves (1) multiwell plate modifications for coating deposition, (2) deposition of combinatorial coating libraries via an automated liquid dispensing robot, (3) coating thickness measurements of cured coatings, (4) preconditioning of coatings via immersion in deionized water, (5) bacterial incubation, (6) plate processing, and (7) data analysis for identification of promising candidates. The details of the method developed are described in this document.     

Simulated molecular evolution in a full combinatorial library

BACKGROUND: The Darwinian concept of 'survival of the fittest' has inspired the development of evolutionary optimization methods to find molecules with desired properties in iterative feedback cycles of synthesis and testing. These methods have recently been applied to the computer-guided heuristic selection of molecules that bind with high affinity to a given biological target. We describe the optimization behavior and performance of genetic algorithms (GAs) that select molecules from a combinatorial library of potential thrombin inhibitors in 'artificial molecular evolution' experiments, on the basis of biological screening results. RESULTS: A full combinatorial library of 15,360 members structurally biased towards the serine protease thrombin was synthesized, and all were tested for their ability to inhibit the protease activity of thrombin. Using the resulting large structure-activity landscape, we simulated the evolutionary selection of potent thrombin inhibitors from this library using GAs. Optimal parameter sets were found (encoding strategy, population size, mutation and cross-over rate) for this artificial molecular evolution. CONCLUSIONS: A GA-based evolutionary selection is a valuable combinatorial optimization strategy to discover compounds with desired properties without needing to synthesize and test all possible combinations (i.e. all molecules). GAs are especially powerful when dealing with very large combinatorial libraries for which synthesis and screening of all members is not possible and/or when only a small number of compounds compared with the library size can be synthesized or tested. The optimization gradient or 'learning' per individual increases when using smaller population sizes and decreases for higher mutation rates.     

UV stabilisation of powder clear coats

Powder coatings are gaining importance in exterior applications such as automotive and architectural finishes. The use of additives in powder coating formulations enhance the durability of the coating by reducing the effects of harmful UV light and providing high temperature stability during processing and curing. Customers' increased demands for better retention of aesthetical and mechanical properties has prompted the development of new additives dedicated to powder coatings. This paper presents an overview of the performance of light stabilizers used in powder coatings.     

Scratch resistance and weatherfastness of uv-curable clearcoats

UV-cuing has found an increasing number of industry allocations over the past decade due to its unique benefits, e.g. solvent free formulations, high cure speed and low temperature processing. In addition to these benefits two additional properties of uv-cured coatings are of today's interest, especially in the automotive industry: scratch resistance and resistance against chemicals. One of the most important requirements for a broad use of uv-curable coatings in the coating industry is that coatings are stable against degradation caused by atmospheric influences since coatings for outdoor use are subject to especially harsh weathering conditions, e.g. uv-light, oxygen, moisture and air pollutants. This weathering leads to a degradation of the polymeric binder. Clearcoats containing photoinitiators based on bis-acylphosphinoxide (“BAPO”) and a combination of hydroxyphenyl-s-triazine uv-absorber and a sterically hindered amine as a light stabilizer package show a very good curing behavior as well as an improved weatherfastness over a long period of time and a good scratch and chemical resistance.     

Thermal degradation and fire performance of intumescent silicone‐based coatings

This paper deals with the thermal degradation and fire performance of silicone‐based coatings for protecting steel. In this study, the fire performance of silicone coatings as virgin or formulated materials is evaluated using two homemade fire testing methodologies: one similar to the “torch test” fire testing method and the other using a heat radiator test. It was shown that the performance of the silicone‐based coating used as thermal barrier can be improved incorporating a modifier (a mixture of polydimethylsiloxane and silica coated by a silane). In this case, silicone‐based coating swells and exhibits same fire performance as commercial intumescent coating at the torch test. It is shown that the incorporation of modifier in the silicone makes it to swell upon heating resulting in the formation of expanded material exhibiting low heat conductivity. Thermal degradation of the coating is also investigated: it occurs in three main steps leading to the formation of a tridimensional network characterized by the formation of Q⁴ structure at high temperature. Copyright © 2012 John Wiley & Sons, Ltd.     

A combinatorial approach for development of materials for optical sensing of gases

We present a combinatorial approach for development of materials for use in optical gas sensors, with oxygen being used as an exemplary target gas. Combinatorial chemistry is shown to be a promising tool for speeding up the search for new sensor materials. The method is based on the use of various polymers, solvents, indicators, plasticizers, and other additives. Solutions of the respective materials are prepared in appropriate organic solvents, and a robotic station is programmed to mix the components. Spots of the sensing materials are deposited in the wells of glass substrates resembling microtiterplates. After drying off the solvent, the sensor spots are automatically analyzed in a test stand, where they are exposed to a carrier gas containing oxygen in various concentrations. Changes in the decay time of fluorescence of the indicator probes are measured and used (along with sensor response time) as a main criterion for sensor assessment. It is shown that the combinatorial approach can reduce the time and effort needed to establish libraries of sensor materials by a factor of at least 1000. We describe in detail the device for preparation of sensor libraries and for testing the respective materials. The potential of the system is demonstrated for the characterization of optical oxygen sensors.     

Characterisation of accelerated ageing devices for prediction of the service life of acrylic-melamine/urethane thermosets

Acrylic-melamine/urethane thermosets are widely used as topcoat materials in the automotive industry. End users and manufacturers require an accurate prediction of the service life of these materials. Despite the significant interest in the topic of service life prediction, no overview of the subject has been presented. This article characterises the influence of light, oxygen and water on these thermosets in an effort to improve the procedures used to evaluate the degradation. Degradation was tracked using two spectroscopic and one mechanical degradation criteria. Based on the evolution of these criteria under artificial and natural ageing, four accelerated ageing devices (SEPAP 12/24, SEPAP ’water spray’, WOM and QUV-B) were used. The results were used to calculate the acceleration factor between natural and artificial weathering to allow for a true service life prediction of these thermosets.     

Affinity Capillary Electrophoresis: From Binding Measurement to Combinatorial Library Screening

Affinity capillary electrophoresis is a new procedure for receptor-ligand binding studies. Since its introduction in the early 1990s, this method has proved valuable in chiral separation of racemates, the measurement of binding constants, the estimation of kinetic rate constants, the determination of stoichiometries, the investigation of electrostatic interactions, the estimation of effective charges and molecular weights of biomolecules, the characterization of enzymatic catalysis, and, most recently, combinatorial library screening in solutions. This technique demands small amounts of samples, involves no radiolabeled materials or chemically immobilized ligands, and does not require changes in spectroscopic characteristics upon binding. This paper reviews the most recent applications of affinity capillary electrophoresis in binding measurement and combinatorial library screening.     

High-throughput screening for combinatorial thin-film library of thermoelectric materials

A high-throughput method has been developed to evaluate the Seebeck coefficient and electrical resistivity of combinatorial thin-film libraries of thermoelectric materials from room temperature to 673 K. Thin-film samples several millimeters in size were deposited on an integrated Al2O3 substrate with embedded lead wires and local heaters for measurement of the thermopower under a controlled temperature gradient. An infrared camera was used for real-time observation of the temperature difference Delta T between two electrical contacts on the sample to obtain the Seebeck coefficient. The Seebeck coefficient and electrical resistivity of constantan thin films were shown to be almost identical to standard data for bulk constantan. High-throughput screening was demonstrated for a thermoelectric Mg-Si-Ge combinatorial library.     

Microfluidic platform for combinatorial synthesis in picolitre droplets

This paper presents a droplet-based microfluidic platform for miniaturized combinatorial synthesis. As a proof of concept, a library of small molecules for early stage drug screening was produced. We present an efficient strategy for producing a 7 × 3 library of potential thrombin inhibitors that can be utilized for other combinatorial synthesis applications. Picolitre droplets containing the first type of reagent (reagents A(1), A(2), …, A(m)) were formed individually in identical microfluidic chips and then stored off chip with the aid of stabilizing surfactants. These droplets were then mixed to form a library of droplets containing reagents A(1-m), each individually compartmentalized, which was reinjected into a second microfluidic chip and combinatorially fused with picolitre droplets containing the second reagent (reagents B(1), B(2), …, B(n)) that were formed on chip. The concept was demonstrated with a three-component Ugi-type reaction involving an amine (reagents A(1-3)), an aldehyde (reagents B(1-7)), and an isocyanide (held constant), to synthesize a library of small molecules with potential thrombin inhibitory activity. Our technique produced 10(6) droplets of each reaction at a rate of 2.3 kHz. Each droplet had a reaction volume of 3.1 pL, at least six orders of magnitude lower than conventional techniques. The droplets can then be divided into aliquots for different downstream screening applications. In addition to medicinal chemistry applications, this combinatorial droplet-based approach holds great potential for other applications that involve sampling large areas of chemical parameter space with minimal reagent consumption; such an approach could be beneficial when optimizing reaction conditions or performing combinatorial reactions aimed at producing novel materials.     

Effects of accelerated aging on mechanical,thermal and morphological behavior of polyurethane/epoxy/fiberglass composites

Wind blades, an important application of polymeric composite materials, are subject to natural weathering. This study aims to evaluate mechanical, thermal and morphological behavior during accelerated aging in three thicknesses of epoxy and fiberglass polyurethane-coated composite plates used in wind turbines, in addition to testing with two acoustic emission techniques. An accelerated aging chamber simulated natural weathering mechanisms for 45, 90, 135 and 180 days. This degradation primarily reduced the mechanical properties of the thinner composites, with some damaged specimens exhibiting fiber-matrix debonding. Thermal properties deteriorated. There were no morphological changes on the polyurethane–epoxy interface; however, degradation occurred in the fiber-matrix interface on the surface exposed to radiation. The degree of chalking indicated coating deterioration on the external surface of the polyurethane. The acoustic wave propagation speed and attenuation coefficient measured prior to mechanical testing indicated the presence of damage areas.     

Design strategies for multielectrode arrays applicable for high-throughput impedance spectroscopy on novel gas sensor materials

This paper reports the first design and fabrication of a 64 multielectrode array for high-throughput impedance spectroscopy. The purpose of this work is the development of a measurement system for the discovery and improvement of sensor materials using combinatorial methods. An array of interdigital capacitors (IDC) screen-printed onto a high-temperature-resistant Al(2)O(3) substrate is determined to be the optimal test plate. The electrode layout, and therefore also the idle capacity, is determined by specific requirements. Calculation of the idle capacity of the IDC as a function of the electrode width and distance allows adjustment and thus optimization of the array. Parasitic effects caused by the leads and contacts are compensated by a software-aided calibration. Apart from the use of the substrates for discovery of new sensor materials, the presented electrode array is also suitable for electrocatalytic applications as well as impedance spectroscopic studies of semiconductors and dielectrics.     

Integrating virtual screening and combinatorial chemistry for accelerated drug discovery

Virtual screening is increasingly being used in drug discovery programs with a growing number of successful applications. Experimental methodologies developed to speed up the drug discovery processes include high-throughput screening and combinatorial chemistry. The complementarities between computational and experimental screenings have been recognized and reviewed in the literature. Computational methods have also been used in the combinatorial chemistry field, in particular in library design. However, the integration of computational and combinatorial chemistry screenings has been attempted only recently. Combinatorial libraries (experimental or virtual) represent a notable source of chemically related compounds. Advances in combinatorial chemistry and deconvolution strategies, have enabled the rapid exploration of novel and dense regions in the chemical space. The present review is focused on the integration of virtual and experimental screening of combinatorial libraries. Applications of virtual screening to discover novel anticancer agents and our ongoing efforts towards the integration of virtual screening and combinatorial chemistry are also discussed.