Photoactivatable compound

Case Study 6.30 Photoactivatable compounds - chromatic orthogonality... 

Explain the following concepts and keywords photochromism photoswitching photoinitiator photoaffinity labelling photo-Wolff rearrangement photoactivatable compound Barton reaction photochemical trigger photolabile linker photoamination redox photosensitization. 

Alternatively, arene displacement can also be photo- rather than thermally-induced. In this respect, we studied the photoactivation of the dinuclear ruthenium-arene complex [ RuCl (rj6-indane) 2(p-2,3-dpp)]2+ (2,3-dpp, 2,3-bis(2-pyridyl)pyrazine) (21). The thermal reactivity of this compound is limited to the stepwise double aquation (which shows biexponential kinetics), but irradiation of the sample results in photoinduced loss of the arene. This photoactivation pathway produces ruthenium species that are more active than their ruthenium-arene precursors (Fig. 18). At the same time, free indane fluoresces 40 times more strongly than bound indane, opening up possibilities to use the arene as a fluorescent marker for imaging purposes. The photoactivation pathway is different from those previously discussed for photoactivated Pt(IV) diazido complexes, as it involves photosubstitution rather than photoreduction. Importantly, the photoactivation mechanism is independent of oxygen (see Section II on photoactivatable platinum drugs) (83). 

In Chapter 2 an account was given of the various classes of molecules that have been used as photoactivatable reagents. This chapter concentrates on the three classes, aryl azides, diazo compounds and diazirines, which can be considered as proven and established. 

The stability of the reagent to the assay conditions should also be ascertained. The instability of azides and diazo compounds towards thiols was mentioned earlier, and it would be prudent to ensure that all new reagents whether they contain familiar photoactivatable groups or not are stable to the prevailing chemical and enzymatic conditions. In an attempt to label the cAMP receptor of D. discoideum, Wallace and Frazier (1979b) found that 8-N rcAMP was converted to NrAMP by the phosphodiesterase of a crude membrane preparation. The NrAMP specifically labeled actin and not the cAMP receptor. 

Caged compounds have the advantage of exhibiting their activities when and where we wish them to do so, in combination with microinjection. Allan et al. S3mthesized a potential photoactivatable caged ABA, the l-(2-nitro)phenylethyl ester (13), which was microinjected into guard cells [16]. ABA was released internally by UV photolysis and subsequently caused stomatal closure. This result suggests intracellular ABA perception. 

Figure 15.4 Examples of caged compounds and other photoactivatable drugs, (a) and (b) on photolysis the o-nitrobenzyl protecting group detaches and releases ATP and cAMP, respectively (c) photosensitive chelator. The cis form of the molecule binds Zn2+ but the trans form does not (d) frequently used photosensitive calcium chelators. Nitr-2 (R = CH3), Nitr-5 (R = H) (e) ICYP-diazirine, a photoaffinity reagent that becomes covalently attached to p-adrenergic receptors upon photolysis.

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