Quantum mechanical–rapid prototyping applied to methane activationRichard P. Muller, Dean M. Philipp, and William A. Goddard IIIMaterials and Process Simulation Center (139-74), California Institute of Technology, Pasadena, California, USA 91125The accuracy of quantum mechanics (QM) calculations have improved to the point at which they are now useful in elucidatingthe detailed mechanisms of industrially important catalytic processes. This, combined with the continued dramatic decreases in thecosts of computing (and the concomitant increases in the costs of experiments), makes it feasible to consider the use of QM indiscovering new catalysts. We illustrate how to apply quantum mechanics to rapidly prototype potential catalysts, by consideringimprovements in the Catalytica Pt catalyst for activating methane to form methanol. The strategy is to first determine the detailedchemical steps of a prototype reaction (in this case, ðbispyrimidineÞPtCl2). Then, we identify critical conditions that must besatisfied for a candidate catalyst to be worth considering further. This allows the vast majority of the candidates to be rapidlyeliminated, permitting a systematic coverage of large numbers of ligands, metals, and solvents to be covered rapidly, enabling thediscovery of new leads. This Quantum Mechanics-Based Rapid Prototyping (QM-RP) approach is the computational-chemistryanalogy of combinatorial chemistry and combinatorial materials science.KEY WORDS: density functional theory; quantum chemistry; homogeneous catalysis; methane activation.1. IntroductionThere has been a revolution in Big Pharma, whereexperimental combinatorial syntheses are now used todevelop rich libraries of compounds that can be rapidlysampled to discover new leads for drug development.Indeed, as discussed in Henry Weinberg’s talk at theGrasselli Irsee Conference, a similar experimentalstrategy has been developed by Symyx for rapidlyprototyping new catalysts. We propose here a computa-tional alternative for rapid prototyping and leaddiscovery of catalysts, which we refer to as QuantumMechanics-Based Rapid Prototyping (QM-RP). Thismethod is useful in suggesting novel catalysts withincreased activity and selectivity. Combined withexperimental verification, QM-RP should sho rten thedesign cycle for developing industrially useful catalysts.We will outline the general strategy for QM-RP usinglow-temperature activation of CH4to form CH3OH asan illustrative example.The conversion of natural gas to liquid products suchas alcohols is of great economic importance. Thetechnologies currently practised in industry first involveconversion of CH4to syng as (carbon monoxide plushydrogen), an energy-intensive, very high temperatur eð850 CÞ process. Fischer –Tropsch chemistry [1] isthen used to produce the oxidized liquid products, whichmay be preceded by water-gas shift to obtain the bestratio of CO to H2. Direct conversion through low-temperature catalysis would have many advantages;however, most current processes are plagued by lowyields and/or high catalyst costs [2–12]. The majorchallenge in developing such direct methods is that theC–H bond in the alkane substrate (e.g., methane) is veryunreactive, whereas the desired partially oxidizedproducts (e.g., alcohols) generated by direct catalyticpathways are usually more reactive than the startingalkanes. Thus, it is too easy to form products that arefully oxidized and commercially unimportant.In 1993, Periana et al., [13] then at CatalyticaCorporation, reported an Hg system that selectivelyoxidized methane to methanol with a 43% one-passyield. An even more effective Pt catalyst was reported in1998 by Periana et al. [14] to convert methane tomethanol with a 72% one-pass yield and 81% selectivity.This Pt catalyst consists of dichloro(-2-f2; 20-bipyrimidylg)platinum(II) (hereafter referred to asbpymðPtÞCl2), shown in figures 1 and 2. It operates inconcentrated super-dry (water-free) sulfuric acid (102%)at 220 C. In sulfuric acid solvent, the product is themethyl bisulfate ester of methanol, requiring addition ofwater to form the product methanol. However, water(which is generated during the conversion process)inhibits the catalyst. This requires an expensive separa-tion process that makes the overall economics unfavor-able. Despite the practical problems, this system is veryeffective and selective for conversi on of methane tomethanol. Hence, we will use this system to illustrate theQM-RP approach.Herein, we will focus on understanding the essentialsteps of the Catalytica Pt catalyst, where the most seriousdifficulties lie in generating a more active catalystcompatible with water. Our calculations have establishedthat the mechanism of the Catalytica Pt catalyst involvesC–H activation step, oxidation, and then functionaliza-To whom correspondence should be addressed.E-mail: wag@ wag.caltech.eduTopics in Catalysis Vol. 23, Nos. 1–4, August 2003 (# 2003) 811022-5528/03/0800–0081/0 # 2003 Plenum Publishing Corporationtion, as indicated in figure 1. Thus, we will considercomplexes in which the Catalytica Pt catalyst has onechloride and one bisulfate ligand in addition to thebispyrimidine ligand. Previous studies indicate this to bethe active form in the concentra ted sulfuric acid solvent(after the first turnover, in which the second Cl ligand is‘‘washed out’’ as HCl). We will concentrate here on theC–H activation step, since it is likely to become ratedetermining for less acidic solvents such as water(oxidation is observed to be rate determining for theCatalytica system in concentrated sulfuric acid [14]).2. General strategy of QM-RPThe QM-RP strategy involves the followi ng steps:(1) Determine the most important reaction pathways(Mechanism) leading to the desired products andany other accessible side products:(a) First, we use ab initio quantum chemistrymethods such as density functional theory(DFT) to optimize the various structures thatmight be relevant. These calculations includesolvation effects on structure and energy. Forcomplex ligands, the QM can be extended toinclude a force-field description of the parts ofthe system, remote from the catalytic center.This may involve mixed quantum mechanics/molecular mechanics (QM/MM) methodol ogy.(b) Next, we determine the key intermediates andtransition-state (TS) structures. Here, it isessential to ensure that the TS is a true saddlepoint (one negative curvature) and that theNNNNPtClClNNHN