Spectral Evolution of a Photochemical Protecting Group for Orthogonal Two-Color Uncaging with Visible Light

Abstract

Caged compounds are molecules rendered functionally inert by derivatization with a photochemical protecting group. We describe the design logic behind the development of a diethylaminocoumarin (DEAC) caging chromophore, DEAC450, that absorbs blue light strongly (ε450 = 43,000 M-1 cm-1), and violet light 10-fold more weakly. The absorption minimum is in the wavelength range (340-360 nm) that is traditionally used for photolysis of many widely used nitroaromatic caged compounds (e.g. 4-carboxymethoxy-5,7-dinitroindolinyl(CDNI)-GABA). We used this chromophore to synthesize DEAC450-caged cAMP and found this probe was very stable towards aqueous hydrolysis in the electronic ground state but was photolyzed with a quantum efficiency of 0.76. When DEAC450-cAMP and CDNI-GABA where co-applied to striatal cholinergic interneurons, the caged compounds were photolyzed in an chromatically orthogonal manner using blue and violet light so as to modulate the neuronal firing rate in a bi-directional way.

Caged compounds for multichromic optical interrogation of neural systems

“…An even larger red shift in the absorption maximum has been reported for the rutheniumbipyridial (RuBi) chromophore (Zayat et al ., , ). Recently, we have developed a new red‐shifted coumarin cage, DEAC450, which also absorbs in a similar region (Olson et al ., ). Thus, there is now a variety of caging chromophores and caged compounds with different photochemical properties available for neurophysiological studies.…”

“…Thus λ 1 and λ 3 can be applied in an arbitrary order such that photolysis with λ 1 can bracket photolysis with λ 3 ; see Olson et al . () and experiments herein.…”

Tightening up the structure, lighting up the pathway: application of molecular constraints and light to manipulate protein folding, self-assembly and function

“…While an in-depth summary [67, 129-132] of the recent advances in this field is beyond the scope of this Review, we would like to highlight several examples to underscore the rapid growth of this exciting research field. For instance, photoremovable protecting groups have been used to trigger acquisition of protein functions [133-135], to investigate enzyme binding and inhibition [136-138], protein translocation [139], chemotactic activity [140], peptide mediated lipid degradation [141], phosphopeptide-binding for signaling pathways [142, 143], and to regulate or control the function or activity of oligonucleotides [144, 145], neurotransmitters [146, 147], hormones [148], and signaling molecules [149, 150]. …”

Kontrolle über Kettenvernetzung und Einzelkettenverknüpfung durch zwei Farben des sichtbaren Lichts

“…[13] Um einen synthetischen Zugang zu solch hierarchischen makromolekularen Architekturen zu erhalten, spielt die orthogonale Ligationschemie von intra-und intermolekularen Kettenreaktionen eine entscheidende Rolle.W ährend klassische, thermisch gesteuerte organische Chemie das Potential innehält solche Systeme zu verwirklichen, würde dies den Einsatz zusätzlicher Reagenzien und chemischer Modifikation der reaktiven Gruppen erfordern. [21,22] Daraus folgt, dass die meisten Systeme nur dann selektiv adressiert werden kçnnen, wenn der Chromophor,d er bei kürzerer Wellenlänge reagiert, vollständig konsumiert worden ist. Im Gegensatz dazu kçnnen anstelle von thermischen Reaktionen photochemische Reaktionen genutzt werden, um nicht nur Zugang zu orts-und zeitaufgelçster Reaktionskontrolle zu erhalten, sondern auch um bestimmte Reaktionskanäle über verschiedene Anregungswellenlängen anzusprechen.…”