www.afm-journal.de www.MaterialsViews.com Click Chemistry in Materials Science Weixian Xi , Timothy F. Scott , Christopher J. Kloxin , and Christopher N. Bowman * with the goals espoused by Sharpless and Despite originating only a little more than a decade ago, click chemistry has coworkers when they fi rst introduced the FEATURE ARTICLE FEATURE become one of the most powerful paradigms in materials science, synthesis, “click” chemistry paradigm, wherein they and modifi cation. By developing and implementing simple, robust chemis- argued that the focus of chemical process selection should be directed towards the tries that do not require diffi cult separations or harsh conditions, the ability to identifi cation, optimization, and simplifi - form, modify, and control the structure of materials on various length scales cation of an overall process. [ 1 ] Thus, this has become more broadly available to those in the materials science com- process identifi cation includes the selec- munity. As such, click chemistry has seen broad implementation in polymer tion of initial target molecules, starting functionalization, surface modifi cation, block copolymer and dendrimer syn- materials, and the reactions used to syn- thesize them, ultimately leading to the thesis, biomaterials fabrication, biofunctionalization, and in many other areas straightforward generation of a compound of materials science. Here, the basic reactions, approaches, and applications with the desired properties via a simple, of click chemistry in materials science are highlighted, and a brief look is robust process. taken into the future enabling developments in this fi eld. The click chemistry philosophy was fi rst introduced in part as a response to the intense and ongoing research focus on the 1. Introduction development of methods for the synthesis of ever more complex natural products. [ 1 ] This chemistry development has historically The marriage between click chemistry and materials science is focused on the creation of stereospecifi c carbon-carbon bonds one that had been destined to occur for many years. Perhaps and typically requires an array of protecting group strategies, more than in any other fi eld, the goal of materials scientists, sequential reactions, and various purifi cation techniques. One engineers, and manufacturers has been to achieve performance main criticism advanced by Sharpless and co-workers is that and a set of desired characteristics in the fi nal material and/or conventional approaches to the natural products synthesis are device in as simple and effective a manner as possible. These too heavily invested in structure and that a great deal of discovery performance targets include specifi cations on mechanical and can be done by utilizing only ‘a few good reactions’. “These reac- physical behavior, such as toughness, modulus, glass transition tions, now denoted as ‘click’ reactions, encompass a utilitarian temperature, refractive index, and clarity, as well as chemical framework and are defi ned by their common attributes of being attributes such as solvent (in)compatibility, surface energy, modular and orthogonal as well as proceeding under simple chemical functionality, and biocompatibility. Process consid- and mild reaction conditions while affording high yields of a erations such as the raw materials, process safety, solvent, and single product with facile purifi cation.” As a consequence of the environmental considerations are also of great importance. simplicity of click reactions, synthesis and chemical modifi ca- This focus on material properties and performance aligns well tion has become far more accessible to a wide community of researchers, particularly in the materials arena, who previously would not have considered venturing into organic chemistry. In W. Xi, Dr. C. N. Bowman fact, a recent highlight identifi ed specifi c criteria for the catego- Department of Chemical and Biological Engineering Materials Science and Engineering Program rization of reactions in polymer chemistry as click reactions that [ 2 ] University of Colorado can serve as a guidepost in this area. Moreover, owing to the Boulder , Colorado 80309–0596 , USA modular nature of the chemistry, it provides a simple framework E-mail: [email protected] for the rapid discovery of new functional materials. Dr. T. F. Scott The original click chemistry paper, presented by Kolb, Finn, Department of Chemical Engineering and Sharpless, described a handful of “spring-loaded” reactions University of Michigan Ann Arbor , Michigan 48109–2136 , USA that meet the click-chemistry standard. These chemistries often Dr. C. J. Kloxin involve heteroatom linkages (i.e., C–X–C) and a signifi cant Department of Materials Science & Engineering thermodynamic driving force (typically >20 kcal/mol). While 150 Academy Street, Newark, Delaware 19716 , USA identifying several reactions that meet these criteria, most Dr. C. J. Kloxin importantly, their paper provides a framework through which Department of Chemical & Biomolecular Engineering to identify click reactions and processes. For example, the cel- University of Delaware 150 Academy Street , Newark, Delaware 19716 , USA ebrated copper-catalyzed azide–alkyne click reaction was obvi- ously not included, as it had not been published until a year DOI: 10.1002/adfm.201302847 later in 2002. [ 3,4 ] Furthermore, although the radical-mediated 2572 wileyonlinelibrary.com © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Funct. Mater. 2014, 24, 2572–2590 www.afm-journal.de www.MaterialsViews.com FEATURE ARTICLE FEATURE thiol-ene reaction was also not included in the seminal click paper, under a wide range of conditions, it clearly exhibits all of Weixian Xi received his B.S. in the characteristics described by Sharpless and co-workers and Chemical Biology from Tsinghua has become ubiquitous in materials science applications. University (China) in 2010. He is a PhD candidate working in the labora- The thiol-ene reaction also demonstrates one of the limita- tory of Dr. Bowman at University tions of the click reaction paradigm as well. In fact, each of the of Colorado Boulder. His research reactions described in the remainder of this manuscript has is focused on sequence-controlled been oft-cited as a click reaction, and each exhibits the click polymer synthesis, and the develop- characteristics over a wide range of conditions and for a wide ment of novel catalysts for “click” range of reaction/coupling types ranging from polymer con- reactions. jugation to surface modifi cation to polymerization to polymer functionalization and many others. That said, prudent selection of reaction conditions, catalyst levels and reactive substrates remains critical even with these broadly useful, robust, nearly Timothy F. Scott is an Assistant Professor in the Department of ideal reactions. For example, in implementing the thiol-ene Chemical Engineering and the reaction, one must be careful to eliminate other substrate- Macromolecular Science and [ 5,6 ] catalyst combinations that cause non-orthogonality, and one Engineering Graduate Program at the must also assure that the initiator and oxygen concentrations University of Michigan. His research are below the level of tolerable side reactions.[ 7,8 ] within the Scott group is focused on In subsequent sections, we will highlight common click reac- the reaction kinetics and thermody- tions and strategies for incorporating click targets into mate- namics of dynamic covalent chemis- rials. We will also demonstrate how just a handful of effi cient tries, and on exploiting the attributes of reactions enables a paradigm shift in materials development. radicals for unique polymer fabrication As will be apparent throughout this article, the click philosophy and manipulation strategies to yield materials for biomedical devices, membrane separators and energy wholly coincides with the goal of creating customizable mate- capture and storage media. rial structures, behavior and performance. This manuscript is meant to highlight the reaction characteristics that make a reaction appropriate as a click reaction, identify the most useful Christopher Kloxin is an Assistant reactions for materials science that have been characterized Professor in the Departments of as click reactions, and discuss representative examples of the Materials Science and Engineering implementation of these reactions in various materials science and Chemical and Biomolecular applications. With more than 1500 papers published in click Engineering at the University of Delaware. His research efforts have chemistry that are relevant to materials or polymer science just focused on new photo-initiated click between 2010 and 2012, it is impossible to review each paper reaction schemes as well as the crea- in the fi eld thoroughly though we hope to highlight the most tion and characterization of covalent common reactions, their mechanisms, and representative adaptable networks. In 2011, he began examples of their implementation in materials science. at the University of Delaware, where his research group utilizes a combi- nation of click and reversible chemical motifs for the design and 2. Click Chemistries synthesis of nature-inspired polymeric materials. In the next sections, we review several of the reactions most fre- Christopher Bowman is a Distinguished quently identifi ed and implemented as click reactions in mate- Professor and the James and Catherine rials science, addressing briefl y their history, mechanism, and Patten Chair in Chemical and Biological