TUTORIAL REVIEW www.rsc.org/csr | Chemical Society Reviews Cooperative catalysis by silica-supported organic functional groups Eric L. Margelefsky,a Ryan K. Zeidanb and Mark E. Davis*a Received 13th February 2008 First published as an Advance Article on the web 17th March 2008 DOI: 10.1039/b710334b Hybrid inorganic–organic materials comprising organic functional groups tethered from silica surfaces are versatile, heterogeneous catalysts. Recent advances have led to the preparation of silica materials containing multiple, different functional groups that can show cooperative catalysis; that is, these functional groups can act together to provide catalytic activity and selectivity superior to what can be obtained from either monofunctional materials or homogeneous catalysts. This tutorial review discusses cooperative catalysis of silica-based catalytic materials, focusing on the cooperative action of acid–base, acid–thiol, amine–urea, and imidazole–alcohol–carboxylate groups. Particular attention is given to the effect of the spatial arrangement of these organic groups and recent developments in the spatial organization of multiple groups on the silica surface. 1. Introduction catalysts. One important way that enzymes accelerate chemicals reactions is through cooperative interactions between precisely The intent of this tutorial review is to summarize some of the positioned reactive groups in the active site. With functional recent advances in a specific class of multifunctional, hetero- groups (metal centers, nucleophiles, acids, bases, hydrogen bond geneous catalysis. A number of research groups have been donors, hydrogen bond accepters) positioned at fixed distances pursuing new and creative approaches towards incorporating to one another in the active site, these groups are capable of multiple functional groups into heterogeneous catalysts in interacting through electrostatic, hydrogen bonding, and cova- such a way that they may act in a cooperative fashion to lent interactions to influence their reactivity. Through these improve the reactivity of the catalyst. In the process of types of interactions, enzymes are capable of significantly accel- exploring such materials, many new materials have been erating reactions (rate enhancement of many orders of magni- reported and some give rise to reactivity unachievable with tude) as well imparting dramatic effects on selectivity. In homogeneous catalysis. A number of different approaches addition to the precise positioning of reactive groups at a fixed have been used to prepare bifunctional heterogeneous cata- distance to one another, the relative positioning of these groups lysts on various support scaffolds, and in this review we within the active site and the formation of hydrophobic/hydro- present a brief summary of the literature pertaining to cata- philic pockets in the active site affects the chemical environment lysis with multiple organic functional groups supported on of the reagents allowing for further rate accelerations, enhanced silica. These materials are significant both from an academic regioselectivity (complete regioselectivity in some cases) as well and industrial standpoint. as complete enantioselectivity for a number of reactions. As an A number of lessons from the basic principles of enzyme example, serine proteases are able to accelerate the cleavage of catalysis can be applied to preparing more efficient synthetic amide bonds, a reaction that is extremely slow uncatalyzed, by a factor of B1012 through cooperative interactions between a Chemical Engineering, California Institute of Technology, Pasadena, California, 91125, USA neighboring nucleophilic alcohol, basic imidazole and acidic 1 b Calando Pharmaceuticals, 2585 Nina St., Pasadena, California, carboxylic acid groups (Fig. 1). By adapting these approaches 91107, USA of spatially positioning functional groups and modifying the Eric Margelefsky was born in Ryan Zeidan was born in De- MarkE.DavisistheWarren Toledo, Ohio, in 1982. He troit, Michigan, in 1980. He and Katharine Schlinger Profes- received his BS in chemical received BS degrees in Chem- sor of Chemical Engineering at engineering from Cornell Uni- istry and Chemical Engineer- the California Institute of Tech- versity in 2004. He is cur- ing from the Massachusetts nology. Professor Davis’ re- rently a fourth-year PhD Institute of Technology in search efforts involve materials student at the California In- 2002. He completed his PhD synthesis in two general areas; stitute of Technology, where in chemistry at the California namely, zeolites and other solids his research involves the de- Institute of Technology in that can be used for molecular Eric L. Margelefsky, sign, synthesis, and character- 2007, and his thesis was en- recognition and catalysis, and Mark E. Davis and ization of spatially-organized titled ‘‘Design of New Multi- polymers for the delivery of Ryan K. Zeidan bifunctional silica catalysts. functional Materials.’’ macromolecular therapeutics such as nucleic acids. 1118 | Chem. Soc. Rev., 2008, 37, 1118–1126 This journal is c The Royal Society of Chemistry 2008 Fig. 1 Schematic of the mechanism of peptide hydrolysis by a serine protease. The enzyme activity is the result of cooperativity among adjacent serine, histidine, and aspartic acid residues. surface of the catalyst, it may be possible to further improve the other hand, the surface groups can act on each other: A upon current heterogeneous catalysts. can activate B and increase its ability to catalyze a reaction, Silica-based materials are commonly used as heterogeneous such as when the imidazole group modifies the nucleophilicity catalysts. Organic functionalization of amorphous, mesopor- of the adjacent alcohol in the case of a serine protease. Finally, ous, and zeolitic silica materials leads to a vast array of the surface groups can act in concert to stabilize a transition catalytically active materials. Most investigators have focused state through multiple weak interactions. Any of these strate- on tethering a single functional group on the surface, often in gies can be used to design a synthetic catalyst that takes order to immobilize an existing homogeneous catalyst (see for advantage of multifunctional cooperativity. instance the review by Molnar and Rac2). Further refinement In this tutorial review, we will focus primarily on several of this methodology has led to the creation of organized pairs examples of cooperative catalysis that have a well-established or clusters of identical surface functional groups. The next step literature precedent: acid–base, amine–urea, acid–thiol (in the in the evolution of these materials is bifunctionalized silica synthesis of bisphenol A), and imidazole–alcohol–carboxylic catalysts where multiple different functional groups are re- acid (as in the catalytic triad of protease enzymes). In each sponsible for improved catalytic activity. In this tutorial re- case, immobilization offers different opportunities and advan- view, we discuss the progress that has been made in this field, tages. ranging from randomly-distributed bifunctional materials to spatially-organized solids. 2.1 Choice of silica support 2. Cooperative catalysis The advantages of heterogeneous catalysts over homogeneous ones are numerous. Traditional heterogeneous catalysts can be In the context of catalysis, the term cooperativity refers to a recycled after a reaction or used continuously in a packed bed system where at least two different catalytic entities act reactor, and the separation of the catalyst from the reaction together to increase the rate of a reaction beyond the sum of mixture is simplified.9 With bifunctionalized materials, other the rates achievable from the individual entities alone. Homo- advantages arise, such as the possibility of new reactivity that geneous cooperativity has been studied using multiple small is impossible in solution. For instance, mutually-destructive molecules3–5 or polyfunctional molecular catalysts.6–8 Numer- functionalities such as acid and base can be immobilized in the ous examples have also been reported of inorganic coopera- same matrix, allowing for their coexistence. Furthermore, the tivity in heterogeneous catalysts by incorporating multiple spatial positioning of the different catalytic groups can be different metal centers onto a support. Here, we focus exclu- modified to tune the catalyst to a particular reaction, which is sively on cooperativity among organic sites on the surface of a impossible when the two groups are both in solution. heterogeneous catalyst (with a specific focus on silica-sup- One of the most common supports for heterogeneous ported organic groups). catalysts is mesoporous silica. Amorphous silica is sometimes There are several different ways in which two different used due to its high surface area and low cost, but the surface functionalities can act cooperatively to catalyze a irregularity of the surface and pore structure can be detri- reaction (Fig. 2). The two groups (A and B) can each activate mental in some applications. Microporous materials, such as a different reactant; A activates a nucleophile and B activates zeolites, can be difficult to functionalize, and the small pore an electrophile, for instance, increasing the reactivity of both. size limits the scope of catalytic reactions. Mesoporous silica, Or the two groups can sequentially activate one reactant; A such as SBA-1510 and MCM-41,11 is easy to functionalize in activates reactant R1 to R10, and B activates R10 to R100.On either a direct synthesis or postsynthetic