COMMUNICATION A Visible-Near Infrared Light Responsive Host-Guest Pair with Nanomolar Affinity in Water Pedro Ferreira, [a] Barbara Ventura, [b] Andrea Barbieri, [b] José P. Da Silva, [c] César A. T. Laia, [a] A. Jorge Parola, [a] * and Nuno Basílio [a] * Dedication ((optional)) Abstract: The discovery of stimuli-responsive high affinity host- guest pairs with potential applications under biological relevant con- ditions is a challenging goal. Herein we report a high-affinity 1:1 complex formed between cucurbit[8]uril and a water soluble photochromic diarylethene derivative. We found that confining the open isomer within the cavity of the receptor induces a red-shift in the absorption spectrum and leads to an enhancement of the photocyclization quantum yield from Φ = 0.04 to Φ = 0.32. This improvement in the photochemical performance enables quantitative photocyclization with visible light that together with the near-infrared light induced ring-opening reaction and the 100-fold selectivity for the closed isomer confirms this as an outstanding light-responsive affinity pair. Supramolecular chemistry provides extraordinary tools to design and realize complex functional materials from molecular building blocks held together by noncovalent bonds. [1,2] Complementary recognition units with high affinity and selectivity for their binding counterparts are required for efficient and robust self-assembled materials. Natural systems provide remarkable examples of highly complementary pairs such as nitrogenous DNA bases, antibody-antigen and ligand-protein that often serve as inspiration for construction of artificial systems. [3–8] Cucurbit[n]urils (CBn) are pumpkin-shaped macrocyclic receptors that display very high-affinity and selectivity for complementary guest molecules in aqueous solution. Binding constants up to ≈10 17 M-1 have been reported which rival the popular biotin-(strep)avidin high-affinity biological pair (K ≈ 10 15 M -1 ). [9–13] CBn can be employed in numerous applications that are based on the extraordinary high affinity displayed by these macrocycles. Examples include recognition, self-assembly and isolation of biomolecules, noncovalent functionalization of biopharmaceuticals, bioimaging and supramolecular materials such as polymers, microcapsules and supramolecular organic frameworks. [14–31] A key feature of supramolecular systems relies on the reversible nature of noncovalent bonds allowing control of association processes using external stimuli. Light is recognized as a superior stimulus for many applications because it allows for remote spatiotemporal control, it is orthogonal to other stimuli and additional reagents are not required. [32,33] While different host-guest complexes formed from CBn and photoresponsive guests had been reported, most of them show binding affinities in the micromolar range or above. [34–40] It is worth noting that some anthracene derivatives are known to form highly stable 1:2 photodimerizable host:guest complexes although with poor reversibility. [41] Herein we report the formation of a photoresponsive host-guest complex between CB8 and a diarylethene derivative, which displays nanomolar affinity in the closed form (1c) and 100-fold lower affinity in the open form (1o). This differential interaction can be used to photoregulate the complexation of high-affinity guest molecules through competitive binding (Scheme 1). Scheme 1. (a) Structures of molecules investigated in this work. (b) Photocontrolled complexation and release of high-affinity guest molecules from CB8. Diarylethenes (DAE) have attracted considerable interest owing to their outstanding photochromic properties. [42] In previously reported CBn:DAE complexes the macrocycle binds to [a] Pedro Ferreira, Dr. César A. T. Laia, Dr. A. Jorge Parola, Dr. Nuno Basílio Laboratório Associado para a Química Verde (LAQV), Rede de Química e Tecnologia (REQUIMTE), Departmento de Química, ,. Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, (Portugal) E-mail: ajp@fct.unl.pt E-mail: nuno.basilio@fct.unl.pt [b] Dr. Barbara Ventura, Dr. Andrea Barbieri Istituto per la Sintesi Organica e la Fotoreattivitá (ISOF) Consiglio Nazionale delle Ricerche (CNR) Via P. Gobetti 101, 40129 Bologna (Italy). [c] Dr. José Paulo Da Silva CCMAR - Centre of Marine Sciences University of Algarve Campus de Gambelas, 8005-139 Faro (Portugal) Supporting information for this article is given via a link at the end of the document a b