Cascade Reactions Catalyzed by Bionanostructures Marco Filice* and Jose M. Palomo* Departamento de Biocata ́ lisis, Instituto de Cata ́ lisis (CSIC) Campus UAM Cantoblanco, 28049 Madrid, Spain ABSTRACT: Cascade reactions are an emerging technology in organic chemistry, introducing elegance and efficiency to synthetic strategies. This Review provides an overview of the novel and recent achievements in cascade processes catalyzed by bionanostructures. The examples here selected demonstrate the advances related to the application of heterogeneous nanocatalystsnanostructures and biomolecules combined by different mannerin efficient cascade processes. Metallic nanoparticles supported on biomolecules, multienzymatic systems or bionanohybrid structures with multicatalytic activities (containing both organometallic and biocatalytic activity) were selectively and efficiently used alone or in cooperative fashion. This Review highlights examples of efficient and interesting catalytic cascade processes in organic chemistry, ultrasensitive biosensing, or energy storage and conversion, underscoring their tremendous future potential in chemical synthesis. KEYWORDS: nanoparticles, nanostructures, biohybrids, cascade catalysis, tandem reaction, domino reaction ■ INTRODUCTION Cascade reactions, typically defined as a consecutive series of chemical reactions proceeding in a concurrent fashion, have attracted scientists’ attention in recent years. One of the main areas in which this strategy plays a pivotal role is in nature with the biosynthesis of natural products. 1-3 Generally, this typology of reaction can be classified in domino, one-pot, or tandem reactions, and the intrinsic advantages correlated to these types of consecutive reactions are clear: atom economy; step-saving and, therefore, high yield; and efficiency of the chemical process. 4-9 From a practical point of view, homogeneous organometallic complexes, organocatalytic molecules, and enzymes have represented and still are successful catalysts for these types of reactions by combining them in different manners. 1,4,6,10-16 However, to efficiently catalyze a cascade reaction, the preparation of solid heterogeneous catalysts with precise control over the location of different functionalities would be generally preferable, but it is still a great challenge. 17-19 During the past decade, 20-24 nanostructured materials (specially the active nanoparticles (NPs)) and biomaterials (as remarkable heterogeneous catalysts for different organic reactions) has undergone explosive growth, thanks to the development of more efficient synthetic methodologies. 25-27 Under a catalytic point of view, nanostructures present many advantages, especially their large surface-to-volume ratio compared to bulk materials. Consequently, as catalysts, NPs can be directly used as such or supported as different nanostructures (nanorods, nanotubes, etc.) 28-31 on a wide set of surfaces, such as inorganic materials (silica, carbon, metal oxides, etc.) or biomolecules (RNA, DNA, polysaccharides, peptides, or proteins). 32-38 In particular, this last strategy possesses the extra capability to generate a greener and sustainable process because these biomolecules can be used as such or as an additive tool to mediate the formation and geometry of nanoparticles in the presence of a reducing agent (typically ascorbic acid or sodium borohydride). 39-41 For example, proteins have been involved in the synthesis of metal nanoparticles 35-38,42 and hybrid nanostructures 34 in aqueous media and at room temperature. Bionanostructures, in which an enzyme is specifically encapsulated in a nanocluster or immobilized on biofunction- alized nanoparticles, 43-45 are another category of catalysts with excellent features in cascade reactions. In particular, heteroge- neous nanohybrid enzyme-metal nanoparticle composites are especially of interest in organic synthesis because of their double or multiple catalytic activities fused in the same entity and simple reutilization strategy (a quite relevant feature from an industrial point of view). 35 Hence, we focus this Review on the most recent advances achieved in this new area of nanocatalysis regarding the use of such bionanostructures in cascade catalysis. Among the various examples encountered in the literature, we selected the most representatives ones describing their synthesis protocols and main application areas, always with the final scope to generally underline to the reader the tremendous intrinsic potential enclosed in this novel but quickly growing strategy. 1. CASCADE REACTION IN ORGANIC SYNTHESIS 1.1. Metallic NP-Catalyzed Cascade Processes. Most of the chemical applications of metallic NPs in catalysis are based on their use as simple NPs or supported in inorganic material. 28-31 However, in recent years, a new approach based on the application of biological entities (RNA, DNA, polysaccharides, peptides, or proteins) as materials for NPs’ immobilization, creating a new type of bionanocomposites, has been developed. 32-38 The possibility to immobilize the NPs by Received: October 31, 2013 Revised: March 21, 2014 Published: March 26, 2014 Review pubs.acs.org/acscatalysis © 2014 American Chemical Society 1588 dx.doi.org/10.1021/cs401005y | ACS Catal. 2014, 4, 1588-1598