Turning “On” and “Off” a Pyridoxal 5′‐Phosphate Mimic Using Light

Abstract

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...

Photoswitching of Copper(I) Chromophores with Dithienylethene‐Based Ligands

“…The optimized geometry of complex 1 in DCM shows as ignificant change in the bond length betweenC (13) and C(14) from 1.36 in the open form to 1.49 in the closed form, consistent with the conclusion that photoirradiation can lead to ring expansion in these metallacycles. [7][8][9][10][11] We wanted to explore applications of these complexes as photoswitchable catalysts for hydroboration since it has been shown that copper(I) complexes can catalyze this reaction with high regioselectivity and yield under mild conditions. In the closed form (1c), the HOMO corresponds to a p orbital of the dithienylethene ring system,w hereas the LUMO corresponds mainly to a p*o rbital Interest in the developmento fa rtificial switchable catalysts is burgeoning because they provide an oninvasive,r eversible methodt oc ontrol reactionr ates.…”

Facile synthesis of photoactive diaryl(hetaryl)cyclopentenes by ionic hydrogenation

“…Besides, it is of interest to study this family of diarylethenes in order to develop different types of light-controlling materials and devices. [11][12][13][14][15][16][17] In addition, the elaboration of an alternative and effective synthetic protocol is one of the major challenges in modern organic synthesis having a high priority in the development of new technologies and smart materials. [18][19][20] However, the synthesis of these compounds remains a difficult task and has a lot of limitations.…”

Bifunctional Molecular Photoswitches Based on Overcrowded Alkenes for Dynamic Control of Catalytic Activity in Michael Addition Reactions

“…External control of catalytic systemsb yl ight is ah ighly challenging and still underdeveloped field of moderno rganic chemistry.I nt he quest for responsive catalytic systems, many advantages arise from the use of light as ac lean, non-invasive stimulus,i nw hich judicious choiceo fi rradiation wavelength may allow precise control over catalyst function, activity and selectivity.Anumber of photoresponsive catalysts have been developed over the last decade, exploiting the established switching properties of azobenzenes,d iarylethenesa nd overcrowded alkenes. [1][2][3][4][5] Promising resultsi np hotochemical control of catalyst activity or selectivity have been achieved through different approaches by harnessing cooperative, [6][7][8][9][10][11][12] steric [13][14][15][16][17][18][19][20] and electronic effects [21][22][23][24][25] of the photo-accessible isomers.…”