The GABAA receptor as a target for photochromic molecules

Abstract

Photochromic ligands, molecules that can be induced to change their physical properties through applied light, are currently the topic of much chemical biology research. This specialized class of small organic structures are, surprisingly to many, fairly common in nature. At the core of a number of natural biological processes lies a small molecule that changes shape or some other measurable property in response to light absorption. For instance, conformational changes invoked by reversible photoisomerization of a retinoid small molecule found in the photoreceptors of the human eye leads to vision. In plants, photoisomerization of a cinnamate moiety leads to altered gene expression. The photosensitive molecule can be viewed simply as a nanosensor of light, much like a photosensitive electrical component might be added to a circuit to sense day versus night to turn an electrical circuit on or off. Synthetic organic chemists and chemical biologists have been, for at least the last 15 years, trying to either mimic or exploit the native photochromism found in nature. Here, we describe the design process to develop a photochromic molecule to be used in neurobiology.

Quantitative assessment of photostability and photostabilisation of Fluvoxamine and its design for actinometry

“…It can serve in the development of new technological AB(2Φ) devices in photomedicine, targeted drug delivery and photo-responsive drug nano-carrier systems. [45][46][47][48] The data provided by such studies may also be of importance for photosafety studies and might be recommended prior to conducting the evermore required in vivo safety studies.…”

“…It can serve in the development of new technological AB(2Φ) devices in photomedicine, targeted drug delivery and photo-responsive drug nano-carrier systems. [45][46][47][48] The data provided by such studies may also be of importance for photosafety studies and might be recommended prior to conducting the evermore required in vivo safety studies. Using Fluvo as an example of photoreversible reaction systems, the model (i) fitted its full kinetic traces; (ii) allowed the determination of the overall-rate constant; (iii) offered the pseudo-rate-constant beta factors as new and reliable kinetic parameters truly reflective of the intra-and inter-experiment rate of photoreactions; (iv) allowed the quantification of effects of photostabilising additives; and (v) presented Fluvo as an accurate and reliable actinometer for the 260-290 nm irradiation range.…”

Montelukast photodegradation: Elucidation of Ф-order kinetics, determination of quantum yields and application to actinometry

“…In fact, the lack of quantum yields' determination is common for a ubiquitous number of AB(2) photoreversible systems used in the pharmaceutical field despite the fact that such systems have found a wide range of applications in numerous research areas ranging from photodynamic materials and photo-nanomedicine (Fomina et al, 2012;Feliciano et al, 2010) to photoresponsive hydrogels and polymeric capsules (Wohl and Engbersen, 2012;Tomatsu et al, 2011). Research in targeted drug delivery, for instance, has recently turned its attention towards triggered drug delivery through the use of stimuli-responsive delivery devices (Fomina et al, 2012;Wohl and Engebersen, 2012;Tomatsu et al, 2011;Feliciano et al, 2010). Lightstimulus represents a particularly attractive means which is currently being actively explored as it can be remotely applied and controlled in space and time thereby affording more precise control over drug release site and dosage (Fomina et al, 2012;Tomatsu et al, 2011).…”

Synapses in the spotlight with synthetic optogenetics

“…We note this, although beyond the scope of this review, as this is the first time that the synthetic optogenetic approach was applied on membrane transporters. Attractively, there are numerous other photochromic agents described in the literature that could, in principle, target GABA‐binding proteins, but to date remain untested . These are ready for the picking by laboratories interested in studying GABA‐mediated synaptic processes by light.…”