The use of light to reversibly change the structure of biologically relevant molecules and turn "on" and "off" important biochemical functions "on-command" offers the biomedical end-user a non-invasive, rapid, reversible, spatial and temporal tool for research and therapy. Applying this control strategy to macromolecules such as oligonucleotides and proteins is challenging because their large size and complexity makes it difficult to target a particular area on the macromolecules for modification, although several impressive examples have been reported. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The alternative is the use of photoresponsive small molecules that play an intimate role in biochemical processes, as either cofactors or inhibitors. Not only would these molecular systems be easier to photoactivate and deactivate than their enzyme partners, they would also provide a more "universal" method to regulate biological function because the same cofactor can be involved in more than one operation.We have recently described how two different colors of light can be used to convert a small molecule between two isomeric forms differing by an order of magnitude in their ability to act as an inhibitor for human carbonic anhydrase. [15] While regulating inhibitors is appealing, [16][17][18] applying the same strategy to enzyme cofactors would provide control over a more diverse set of biochemical systems. Cofactors have all the earmarks of a suitable photoresponsive target. They tend to be small in size, structurally simple and easy to modify and study, while still allowing for ultimate control over the enzyme activity. Here, we take a first logical step by using a well-known enzyme cofactor as the inspiration in our design of a proof-of-concept demonstration. We show how our biomimetic system acts as a photoswitchable catalyst for a biochemical reaction. [19] The biologically active form of vitamin B 6 , pyridoxal 5'phosphate (PLP), is a versatile enzyme cofactor responsible for amino acid metabolism in all organisms from bacteria to humans. [20] Its participation in a diverse range of enzymatic reactions including transamination, racemization, decarboxylation, and numerous elimination and replacement processes makes it unrivalled. [21] It is a particularly inspiring cofactor for our proof-of-concept design because it can catalyze many processes without the presence of an enzyme. [22,23] It is also the role-model target of the studies described in this report.The structural features responsible for the action of PLP are the aldehyde and pyridinium functional groups, which are electronically connected to each other through bonds (Scheme 1). This intimate connectivity allows any molecule attached to the aldehyde to "sense" the electron withdrawing nature of the positively charged heterocycle. An example of this is the aldimine generated when an amino acid condenses with PLP (Scheme 1) and it is this Schiff base that is responsible for the enormous range of reactions the cofactor catalyzes. [24] The pyridinium group...

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A convenient and versatile protocol to encapsulate lanthanide doped upconverting nanoparticles by an amphiphilic polymer shell containing photoresponsive diarylethene chromophores was developed. The assemblies are all water-soluble and fluoresce in the visible region of the spectrum when excited with 980 nm near-infrared light. The fluorescent emission can be selectively and reversibly modulated by alternatively irradiating the photoresponsive nanoparticles with UV light and visible light, which triggers ring-closing and ring-opening reactions of the chromophores, respectively. Fluorescence lifetime experiments suggest that the quenching mechanism is a combination of energy transfer and emission-reabsorption processes. These photoresponsive upconverting nanoparticles have the potential to advance bioimaging and other applications in nanophotonics.

A photoresponsive small molecule undergoes a ring-opening reaction when exposed to visible light and becomes an active inhibitor of the enzyme protein kinase C. This "turning on" of enzyme inhibition with light puts control into the hands of the user, creating the opportunity to regulate when and where enzyme catalysis takes place.

A photoresponsive amphiphilic polymer was synthesized and used to encapsulate upconverting lanthanide-doped nanoparticles to produce a novel water-dispersible nanoassembly with a high loading of emission quenchers. The nanoassembly exhibits fluorescent emission in the visible region upon irradiation with 980 nm light, which can be reversibly modulated by toggling the isomeric state of photoresponsive chromophores attached to the polymer’s backbone using UV and visible light. Photon counting experiments show that the quenching mechanism for this new nanoassembly is a combination of Förster resonance energy transfer (FRET) and emission-reabsorption. Compared to the similar nanoassembly prepared from a reported “plug-and-play” method, this new nanoassembly has higher overall quenching efficiency due to the increased photoswitch loading (14 times compared to the existing nanoassembly).

Licht wird verwendet, um ein photoresponsives Mimetikum des Cofactors Pyridoxalphosphat zwischen zwei Isomeren zu schalten, von denen nur eines die Racemisierung einer Aminosäure katalysieren kann. Die Funktion beruht auf dem Herstellen und Unterbrechen der elektronischen Kommunikation zwischen den beiden Katalysatorkomponenten, einem Aldehyd und einem Pyridiniumkation.

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In this protocol, we first describe a procedure to synthesize lanthanide doped upconverting nanoparticles (UCNPs). We then demonstrate how to generate amphiphilic polymers in situ, and describe a protocol to encapsulate the prepared UCNPs and different organic dye molecules (porphyrins and diarylethenes) using polymer shells to form stable water-dispersible nanoassemblies. The nanoassembly samples containing both the UCNPs and the diarylethene organic dyes have interesting photochemical and photophysical properties. Upon 365 nm UV irradiation, the diarylethene group undergoes a visual color change. When the samples are irradiated with visible light of another specific wavelength, the color fades and the samples return to the initial colorless state. The samples also emit visible light from the UCNPs upon irradiation with 980 nm near-infrared light. The emission intensity of the samples can be tuned through alternate irradiation with UV and visible light. Modulation of fluorescence can be performed for many cycles without observable degradation of the samples. This versatile encapsulation procedure allows for the transfer of hydrophobic molecules and nanoparticles from an organic solvent to an aqueous medium. The polymer helps to maintain a lipid-like microenvironment for the organic molecules to aid in preservation of their photochemical behavior in water. Thus this method is ideal to prepare water-dispersible photoresponsive systems. The use of near-infrared light to activate upconverting nanoparticles allows for lower energy light to be used to activate photoreactions instead of more harmful ultraviolet light.