Combinatorial Chemistry & High Throughput Screening - Volume 10, Issue 1, 2007

As Combinatorial Chemistry & High Throughput Screening begins its tenth year of publication, I would like to look back at some of the highlights of these last ten years. The initial effort to organize this journal was carried out in 1997 by John M. Pezzuto, when he was my colleague here at the University of Illinois, Chicago. Due to a wealth of other commitments, John Pezzuto stepped down from his role as the founding editor of the journal, and I accepted the position as Editor-in-Chief. Today, John Pezzuto is on the Editorial Board of CCHTS and is Professor and founding Dean of the College of Pharmacy of the University of Hawaii. The first issue of CCHTS, consisting of four issues, appeared in 1998. The next year, the publication frequency was increased from four to six issues per year. Due to the worldwide growth of research in combinatorial chemistry and high throughput screening, the publication frequency of CCHTS was increased again to eight issues when volume 4 was published in 2001. At eight issues per year, CCHTS became the leader in this field. By 2006, the large number of papers in the publication queue prompted us to expand volume 9 to 10 issues per year, which established a new standard. The benefit of frequent publication is that CCHTS has minimal time between paper acceptance and publication. From its inception, CCHTS has occupied a unique position in the peer reviewed literature by focusing on the publication of review articles and original research papers in combinatorial chemistry, high throughput screening, and the interface of these related fields. To the best of my knowledge, no other journal specializes in this combination of topics. In addition, the editorial policy of CCHTS has always been to publish papers in all areas of combinatorial chemistry and high-throughput screening, and this policy will continue with volume 10. For example, readers of CCHTS this year should expect to see papers ranging from the use of high throughput screening for the optimization of solid-phase catalysts for different chemical reactions (see this issue) to combinatorial library synthesis using multicomponent reactions. A reflection of the breadth of the readership of CCHTS is the citation of papers published in this journal. Please note the ten most cited papers appearing to date in CCHTS, which are cited in order below [1-10]. Approximately half of these papers concern combinatorial chemistry, such as combinatorial chemical synthesis or computational rational design of combinatorial libraries, and the other half of these highly cited papers address high throughput screening methods and applications, such as the application of fluorescence polarization to HTS or virtual screening of combinatorial libraries. I would like to congratulate the corresponding author Peter Schulz-Knappe and his colleagues for contributing the most highly cited paper so far to CCHTS [1]. In this paper, the term, “peptidomics”, was coined, which is defined as the process of analyzing and visualizing peptides and small proteins from biological samples. In addition, I would like to acknowledge Reto Crameri who served as the guest editor for the special issue in which this peptidomics paper appeared. As in the past, regular issues of CCHTS will be alternated with special issues focusing on a single topic of current interest. Some of these special issues will be organized by members of our Editorial Board and others will be organized by guest editors who will introduce fresh perspectives and unique expertise to the journal. Readers should note that all papers published in CCHTS are peer reviewed whether they appear in a special issue on a hot topic or in a regular issue. Papers published in CCHTS receive high visibility, since they are abstracted and indexed by the major services including Chemical Abstracts, BIOSIS, CAB Abstracts, EMBASE, BIOBASE, Science Citation Index-Expanded, MEDLINE, and Current Contents (Life Sciences). Through the combination of frequent publication, peer review and high visibility, Combinatorial Chemistry & High Throughput Screening remains a unique and essential scientific journal defining the intersection of the interdependent disciplines of combinatorial chemistry and HTS. I would like to thank the distinguished members of the Editorial Board, the Regional Editors, the guest editors, the authors, and of course you, the readers, for the continuing success of our journal. The 10 most cited papers appearing in Combinatorial Chemistry & High Throughput Screening from 1998 to 2006 (according to the Web-of-Science, produced by Thomson Scientific, Philadelphia, PA; accessed on-line January 4, 2007 at http://scientific.thompson.com)..

These special issues (Vol. 10, No. 1 and Vol. 10, No. 2) are devoted to progress in the area of Combinatorial Heterogeneous Catalysis (CHC), which can be considered to be the general application of combinatorial and high-throughput methods and strategies in materials research. Heterogeneous catalysis plays a vital role if our everyday lives. All pollution-free and environmentally friendly industrial processes in oil refineries, chemical plants, and power energy stations need highly active and selective catalysts. Catalysts are used in cars and trucks to remove harmful products of incomplete oxidation of gasoline or diesel fuel. The plastics used in everyday life are prepared by applying very specific highly active and selective catalysts, and this list can be continued. Better catalysts reduce productions costs, reduce the formation of wasteful by-products, and help to decrease atmospheric pollution. These are the main reasons that the search for new and better catalysts is a permanent R & D task. In general, combinatorial approaches are intended to find the optimum formulation in various pharmaceutical or engineering materials including catalysts, with the shortest interval and minimum amount of unit cost. In this case the focus is laid on the optimum performance with decreased overall costs. All combinatorial approaches are based on the diversity of the system investigated. This diversity determines the parameter space where the optimum performance may be found. In combinatorial materials research, including CHC, the following key components of diversity can be distinguished: (i) compositional; (ii) process; and (iii) structural. The structural diversity is determined by the first two components. In order to move in a large experimental space towards the optimum performance, the following requirements must be fulfilled: (i) high throughput methods in synthesis, testing, and analysis; (ii) highly reliable and reproducible analytical methods; (iii) effective optimization and information mining tools; and (iv) appropriate data handling and management methods. Today, combinatorial heterogeneous catalysis is a well-acknowledged area of catalysis sciences, although a definite part of our scientific community still remains quite critical. Methods of combinatorial catalysis are widely used both in applied and academic laboratories. Symyx Technologies was the first company devoted to the area of combinatorial heterogeneous catalysis. Among the followers are the Dutch company Avantium Technologies, the German group “hte GmbH”, etc. In the last 10 years, most of the large oil and chemical companies created their own laboratories in combinatorial catalysis. In academia, various combinatorial heterogeneous laboratories have emerged in various countries, such as Australia, Japan, Korea, Singapore, Germany, the Netherlands, Belgium, France, UK, Norway, Spain, Hungary, Canada, USA, China, India, and Mexico. These laboratories may be considered as the pioneers in this field. Consequently, there is considerable geographical diversity in the location of key laboratories. The importance of this field has been documented by various international meetings fully or partly devoted to CHC. Most of the international meetings in the field of heterogeneous catalysis have an independent section devoted fully to high throughput and combinatorial methods. In several highly ranked meetings (Europacat, International Catalysis Congress), round table discussions took place that were excellent forums for listening to both the pros and the cons of CHC. It should be mentioned that there is a special “heterogeneous catalysis” section at the Gordon Research Conferences devoted to the field of combinatorial materials research. If we look back to the first publications in the area of CHS, we see that the focus has been on the methodology and the use of high-throughput techniques and technologies. In this period, gas phase catalytic reactions were usually investigated. Today, after ten years of practice in this field, the area of activity in CHC has been expanded considerably. Combinatorial methods are used today to develop catalysts for applications such as (i) gas and liquid phase reaction both at atmospheric and high pressures; (ii) electro-catalysts for fuel cell technology; and (iii) photo-catalysts for water splitting and environmental control. New sophisticated preparation methods, such as inkjet printing, laser ablation, co-spattering, etc., are also being applied........

Combinatorial synthesis and screening technique have been applied to investigate the catalytic activity and selectivity of ternary and quaternary mixed-metal oxide catalysts for the selective oxidation of propane. The catalyst libraries were prepared via a modified sol-gel method using a synthesis robot and library design software, and examined for the catalytic activities in a simple high-throughput reactor system connected to a mass spectrometer for product analysis. Ternary Mo-Cr-Te, V-Cr-Sb, and Mo-V-Cr catalysts have been selected for potential candidate by composition spread approach. In a next generation composition spread library, the composition space of these three ternary compositions was sampled. Screening of this 198-member library provided substantial evidence that each ternary system has its own optimum composition where acrolein formation is highest. In addition, the composition space of the quaternary reference system Mo-V-Te-Nb mixed-oxides has also been prepared and sampled.

This work shows the application of support vector machines (SVM) for modelling and prediction of zeolite synthesis, when using the gel molar ratios as model input (synthesis descriptors). Experimental data includes the synthesis results of a multi-level factorial experimental design of the system TEA:SiO2:Na2O:Al2O3:H2O. The few parameters of the SVM model were studied and the fitting performance is compared with the ones obtained with other machine learning models such as neural networks and classification trees. SVM models show very good prediction performances and generalization capacity in zeolite synthesis prediction. They may overcome overfitting problems observed sometimes for neural networks. It is also studied the influence of the type of material descriptors used as model output.

The catalytic oxidation of carbon monoxide to carbon dioxide is an important process used in several areas such as respiratory protection, industrial air purification, automotive emissions control, CO clean-up of flue gases and fuel cells. Research in this area has mainly focused on the improvement of catalytic activity at low temperatures. Numerous catalyst systems have been proposed, including those based on Pt, Pd, Rh, Ru, Au, Ag, and Cu, supported on refractory or reducible carriers or dispersed in perovskites. Well known commercial catalyst formulations for room temperature CO oxidation are based on CuMn2O4 (hopcalite) and CuCoAgMnOx mixed oxides. We have applied high-throughput and combinatorial methodologies to the discovery of more efficient catalysts for low temperature CO oxidation. The screening approach was based on a hierarchy of qualitative and semi-quantitative primary screens for the discovery of hits, and quantitative secondary screens for hit confirmation, lead optimization and scale-up. Parallel IR thermography was the primary screen, allowing one wafer-formatted library of 256 catalysts to be screened in approximately 1 hour. Multichannel fixed bed reactors equipped with imaging reflection FTIR spectroscopy or GC were used for secondary screening. Novel RuCoCe compositions were discovered and optimized for CO oxidation and the effect of doping was investigated for supported and bulk mixed oxide catalysts. Another family of active hits that compare favorably with the Pt/Al2O3 benchmark is based on RuSn, where Sn can be used as a dopant (e.g. RuSn/SiO2) and/or as a high surface area carrier (e.g., SnO2 or Sn containing mixed metal oxides). Also, RuCu binary compositions were found to be active after a reduction pretreatment with hydrogen.

The objective of this work is the construction of a correlation between characteristics of heterogeneous catalysts, encoded in a descriptor vector, and their experimentally measured performances in the propene oxidation reaction. In this paper the key issue in the modeling process, namely the selection of adequate input variables, is explored. Several data-driven feature selection strategies were applied in order to obtain an estimate of the differences in variance and information content of various attributes, furthermore to compare their relative importance. Quantitative property activity relationship techniques using probabilistic neural networks have been used for the creation of various semi-empirical models. Finally, a robust classification model, assigning selected attributes of solid compounds as input to an appropriate performance class in the model reaction was obtained. It has been evident that the mathematical support for the primary attributes set proposed by chemists can be highly desirable.

Complex multi-element lead structures of mixed metal oxides that may be identified as hits during high throughput experimentation (HTE) campaigns, can be deconvoluted retrospectively on the basis of simple binary and ternary oxides as illustrated in the current example of a hit found in an ammoxidation reaction. On the basis of the performance of the simple binary and ternary mixed metal oxides structure property relationships can be established, that give insight into the roles of the different components of the complex mixed metal oxides and may also help in establishing a reaction mechanism and converting the hit into a development candidate.

A multi-criteria optimisation procedure based on genetic algorithms is carried out in search of advanced heterogeneous catalysts for total oxidation. Simple but flexible software routines have been created to be applied within a search space of more then 150,000 individuals. The general catalyst design includes mono-, bi- and trimetallic compositions assembled out of 49 different metals and depleted on an Al2O3 support in up to nine amount levels. As an efficient tool for high-throughput screening and perfectly matched to the requirements of heterogeneous gas phase catalysis - especially for applications technically run in honeycomb structures - the multi-channel monolith reactor is implemented to evaluate the catalyst performances. Out of a multi-component feed-gas, the conversion rates of carbon monoxide (CO) and a model hydrocarbon (HC) are monitored in parallel. In combination with further restrictions to preparation and pretreatment a primary screening can be conducted, promising to provide results close to technically applied catalysts. Presented are the resulting performances of the optimisation process for the first catalyst generations and the prospect of its auto-adaptation to specified optimisation goals.

In the present work, the role and the effect of platinum and gold on the catalytic performance of ceria supported tri-metallic Pt-Pd-Au catalysts have been studied. The optimum composition of these tri-metallic supported catalysts has been discovered using methods and tools of combinatorial catalyst library design. Detailed catalytic, spectroscopic and physico-chemical characterization of catalysts in the vicinity of the optimum in the given compositional space has been performed. The temperature-programmed oxidation of methane revealed that the addition of Pt and Au to Pd/CeO2 catalyst resulted in higher conversion values in the whole investigated temperature range compared to the monometallic Pd catalyst. The time-on-stream experiments provided further evidence for the high-stability of tri-metallic catalysts compared to the monometallic one. Kinetic studies revealed the stronger adsorption of methane on Pt-Pd/CeO2 catalysts than over Pd/CeO2. XPS analysis showed that Pt and Au stabilize Pd in a more reduced form even under condition of methane oxidation. FTIR spectroscopy of adsorbed CO and hydrogen TPD measurements provided indirect evidences for alloying of Pt and Au with Pd. CO chemisorption data indicated that tri-metallic catalysts have increased accessible metallic surface area. It is suggested that advantageous catalytic properties of tri-metallic Pt-Au-Pd/CeO2 catalysts compared to the monometallic one can be attributed to (i) suppression of the formation of ionic forms of Pd(II), (ii) reaching an optimum ratio between Pd0 and PdO species, and (iii) stabilization of Pd in high dispersion. The results also indicate that Pd0 - PdO ensemble sites are required for methane activation.