Photoinduced Release of Neurotransmitter Amino Acids from Coumarin‐Fused Julolidine Ester Cages

Abstract

The photoinduced release of several neurotransmitter amino acids (glycine, alanine, glutamic acid, β‐alanine and γ‐aminobutyric acid) was accomplished from ester cages based on a new photoremovable protecting group consisting of a coumarin built on the julolidine nucleus, namely a (11‐oxo‐2,3,5,6,7,11‐hexahydro‐1H‐pyrano[2,3‐f]pyrido[3,2,1‐ij]quinolin‐9‐yl)methyl group. Photolysis and steady‐state sensitization studies revealed that release of the active molecule occurred in short irradiation times at long wavelengths, with a very promising performance at 419 nm. Given the interest in the development of novel protecting groups that are cleavable with UV A or even visible radiation, it was found that a structural modification in the coumarin ring by assembly of a fused julolidine leads to a promising photolabile protecting group for organic synthesis and also for bioapplications.

Photoactivable heterocyclic cages in a comparative release study of butyric acid as a model drug

“…This is indicative of the presence of different excited state species and the outcome of these measurements is presented in Table 3. The behaviour seen is in keeping with our previous observations [19,20,26] and the longer-lived emission can relate to unquenched (potentially cleaved) fluorophore. The shorter-lived decays are attributed to charge transfer states, caused by the presence of the conjugate upon excitation, with the possibility of the formation of an ion pair that can either recombine or progress to a cleaved pair.…”

“…On the other hand, compound 8, considering the 350 nm values in Table 2, has one of the lowest photochemical yields and exhibits the longest-lived average lifetime. It is a moot point in this case whether the quantity of the longest-lived component relates to cleaved photoproduct, as we have previously shown using decay associated spectra and a kinetic measurement [26], or can reflect on the strength of coupling to the conjugate. This will be the basis of further work, although the fact that 12 exhibits a high photochemical yield, while displaying the shortest average lifetime may indicate the latter.…”

“…For the assembly of the heterocyclic benzyl type ester cages 8-12, several bromo-or chloromethylated heteroaromatics based on acridine 2, naphtho[2,1-b]pyran 3-5 and a 3H-benzopyran fused julolidine 6 were reacted with the model acid in the presence of potassium fluoride in DMF at room temperature (Scheme 1, Table 1). Fused pyrans 3-6 resulted from a Pechmann condensation between ethyl 4-chloro-3-oxobutanoate and 3-methoxy-2-naphthol, 6-methoxy-2-naphthol, 7-methoxy-2-naphthol [25] and 1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-8-ol (trivially named 8-hydroxyjulolidine) [26], respectively. With the purpose of replacing the carbonyl by a thiocarbonyl group at the naphtho[2,1-b]pyran conjugates 9-11, these compounds were reacted with Lawesson's reagent in toluene, under reflux conditions [29], giving rise to the corresponding thionaphthopyran conjugates 13-15.…”

“…All reagents were used as received. Compounds 5, 6 and 11 were synthesised as previously reported [20,25,26].…”

Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages

“…In recent years, our research has been focused on the release of bioactive molecules mainly from heterocyclic cages, specifically designed for being triggered by light, to act as photoremovable protecting groups and phototriggers. Coumarin, benzocoumarin and pyrene derivatives, among other moieties, have been designed and applied in the caging of amino acids, neurotransmitters, biogenic amines, butyric acid and 5-aminolevulinic acid (Fernandes et al 2007;Fernandes et al 2008;Soares et al 2010;Hungerford et al 2010;Fonseca et al 2010;Soares et al 2012;Piloto et al 2013;Fernandes et al 2013;Piloto et al 2015;Soares et al 2015a;Soares et al 2015b;Soares et al 2017).…”