Synthesis, Photochromic Properties, and Light-Controlled Metal Complexation of a Naphthopyran Derivative

Abstract

A light-controlled reversible binding switch based on photochromic 3H-naphtho [2,1-b]pyran is under development for studying cellular oscillatory calcium signals. The binding affinities of the closed and open forms of substituted naphthopyran 1 for Ca 2+ , Mg 2+ , and Sr 2+ in buffer were determined. The photochemically ring-opened form of the receptor exhibited increased affinity compared to the thermally stable closed form of the receptor. The binding affinity difference for Ca 2+ was ∼77-fold at pH 7.6. Calcium (Ca 2+ ) is a second messenger in many cell types, where it is used to translate extracellular signals into a wide variety of intracellular events. 1 Important cellular processes are controlled by Ca 2+ , and many disease states are associated with defects in the calcium signalosome. Manipulation of Ca 2+ concentration in cells through cage compounds is an important tool for learning about this widespread signaling system. 2 Caged Ca 2+ compounds undergo irreversible photochemical reactions that either release or take up Ca 2+ when triggered. However, cage compounds are less well suited to the examination of oscillatory calcium signals, which may encode information through both amplitude and frequency modulation. The origin of these oscillatory signals is known, but their effects at a molecular level are less well understood. There is a need to develop new methodologies to study the effects of spatiotemporal changes in Ca 2+ concentration. In the present work, we report the synthesis and characterization of compound 1, a new watersoluble 3H-naphtho[2,1-b]pyran with an iminodiacetic acid substituent at position 5 ( Figure 1). This compound is designed so that the open form of 1 will exhibit a higher affinity for Ca 2+ than the closed form. The binding affinities of closed and open forms of compound 1 were determined, and the effects of buffer composition and pH, on this reversible calcium binding photoswitch were also examined.Naphthopyran chelator 1 was obtained in five steps (Scheme 1 and Supporting Information) with an overall yield of 11%. Compound 1 is soluble up to ∼5.7 × 10 -4 M in aqueous solutions buffered at pH 8.7.Complexation of the closed form of 1 with metal ions was examined spectroscopically. The UV-vis spectra of 1 show minimal changes upon addition of excess Mg 2+ , Ca 2+ , and Sr 2+ ( Figure S1, Supporting Information). The addition of metal ions to the closed form of 1 did not result in any detectable thermal ring opening induced by metal complexation, unlike that observed for some photochromic chelators. 5d,7d,8 Small but significant and reproducible 1 H NMR shifts were observed upon addition of metal ions (Table S2, Supporting Information). One or more aromatic protons moved downfield upon addition of all metals to the closed form of 1. The methylene protons only shifted when calcium was added, and they moved upfield. The same pattern of complexation-induced shifting, but with smaller magnitudes, was also observed upon the addition of the same three metals to phenyliminodi...

Molecular switches as photocontrollable “smart” receptors

“…An example of this concept was reported. 46 Molecule 24a is a 3H-naphtho[2,1-b]pyran with an aminodiacetic acid substituent in the 5 position. The photoinduced ring opening by continuous UV irradiation generates the isomer 24b which exhibits higher affinity for Ca 2+ than the closed form.…”

X-ray, kinetics and DFT studies of photochromic substituted benzothiazolinic spiropyrans

“…Our interest in this subject derives from the fact that suitably functionalized spiropyran compounds have potential for application in mimicking calcium oscillations in biological systems [14–15]. While spirobisbenzopyran compounds do not have appropriate photophysical properties at room temperature, benzothiazolinic spiropyran compounds offer a significant improvement.…”

Photoresponsive Ion Extraction/Release Systems: Dynamic Ion Optodes for Calcium and Sodium Based on Photochromic Spiropyran

“…20,21 For other ionic species photoactive chelating compounds were used for reversible 22−25 and irreversible affinity changes (photo cages). 26 In our work, however, the driving force for triggered ion exchange is the change in p K a of a photoactive chromoionophore.…”