Fluorinated retinoids and carotenoids.

Methods of preparing fluorinated retinoids with labels located on odd-numbered carbons as well on even-numbered carbons and those containing trifluoromethyl groups are reviewed. The use of such retinoids in studies of protein-bound species is summarized, including the application of (19)F NMR spectroscopy for elucidating the mechanism of cis/trans isomerization, restricted rotation within the protein binding pocket, and identification of specific protein-substrate interactions. The fluorine label was also useful for wavelength attenuation of protein-bound species (including formation of NIR absorbing pigments) and for other unique applications. The more limited studies available on fluorinated carotenoids are also reviewed.

Fluoro derivatives of retinal illuminate the decisive role of the C(12)-H element in photoisomerization and rhodopsin activation.

Rhodopsin, the visual pigment of the vertebrate rod cell, is among the best investigated members of the G-protein-coupled receptor family. Within this family a unique characteristic of visual pigments is their covalently bound chromophore, 11-cis retinal, which acts as an inverse agonist. Upon illumination it can be transformed into the all-trans isomer that acts as a full agonist. This photoisomerization process is extremely efficient: 2 out of 3 photons are effective, full stereoselectivity is achieved, and stereoinversion occurs within 200 fs. The mechanism behind this process is still not really understood, although the available evidence points at the twisted C(9)-C(13) segment of the 11-cis ligand as the quintessence. To further dissect the role of this segment, we have generated the 10-fluoro, 12-fluoro, and 14-fluoro analogues of rhodopsin. A fluoro substituent brings in only little more volume than hydrogen, but considerably more mass and polarizability. The analogue pigments were compared to rhodopsin with respect to their photosensitivity (quantum yield), light-induced structural transitions (UV-vis and FT-IR spectroscopy), and signaling activity (G protein activation rate). We find that 14-F substitution is quite neutral, while 10-F and 12-F substitutions exert significant but distinct effects. The 10-F pigment exhibits a quantum yield similar to that of rhodopsin (0.65) but strongly perturbed thermodynamics of the structural transitions following photoactivation and only 20% of the native signaling activity. The 12-F pigment exhibits a significantly decreased quantum yield (0.47) and signaling activity (30%) but mixed effects on the structural transitions. These properties are compared to those of the corresponding methyl derivatives. We conclude that rotation of the C(12)-H bond of the rhodopsin chromophore is a major rate-limiting factor in the photoisomerization process, while the C(10)-H moiety plays a dominant role in ligand relaxation and further rearrangements following photoactivation.

A comprehensive investigation of the interrelationships between spectroscopy and photochemistry and substituents of some azulenic derivatives.

Several azulenic dyes, including six azulene hydrocarbons, two azulene aldehydes, and two olefinic azulenes, have been synthesized to survey their photophysics and photochemistry. These azulenes display S(2)-->S(0) emission, but with several differences. This is the most remarkable characteristic of the effect of orbital control on color and excited state properties of the azulenic compounds. This paper emphasizes how emission spectra and photochemistry of azulenic compounds are influenced by their chemical structure and solvent. The emission spectra of the azulene hydrocarbons suggest that their excited state properties can be controlled by their molecular structure and size. It was confirmed by emission and (1)H NMR spectroscopy that azulene monoaldehyde is protonated in a strong acid, such as trifluoroacetic acid (TFA). Photochemistry of styrylazulenes was observed during irradiation. Azulenic compounds are thermally stable and color tunable, and hence they are good candidates as non-linear optical materials. Based on their unique photochemical and photophysical characteristics, novel azulenic dyes can be constructed for different uses.

Mechanism of photoisomerization of 1-naphthyl-2-phenylethylenes in organic glasses.

Photoisomerization reactions of cis isomers of 1-beta-naphthyl-2-phenylethylene, an o-methylated homolog and 1-alpha-naphthyl-2-phenylethylene in organic glasses at liquid nitrogen temperature were studied. Reactions were followed by changes in UV-absorption spectra of the irradiated samples. Formation of an unstable trans-photoproduct was detected only with the o-methylated homolog. The results are consistent with high regioselective Hula-twist photoisomerization at the benzylic sites of the three compounds examined. Calculated data on relative energies of the conformers of both the cis and the trans isomers are in agreement with the suspected conformational population of the starting materials and the photoproducts.

Mechanisms of photoisomerization of polyenes in confined media: from organic glasses to protein binding cavities.

Photochemical reactivities of model organic systems (stilbene and diphenylbutadiene) in organic glasses were first examined and compared with those in solution and in organized media. These observations were in turn compared with reactivities of polyene chromophores in protein binding cavities (specifically PYP, rhodopsin and bacteriorhodopsin). The obvious conclusion is that the preference for the most volume-conserving Hula-twist mechanism isomerization in organic glasses is because of the close interaction between the guest and the host molecules. In organized media (zeolites, crystals and protein binding cavities), the residual empty space coupled with any specific guest-host interactions that are characteristic of a given system, could lead to involvement of the more volume-demanding one-bond-flip (i.e. torsional relaxation) or bicycle-pedal or an extended HT process in photoisomerization.

Stilbene analogs in Hula-twist photoisomerization.

Photoisomerization of several cis- or Z-stilbene analogs and two E-analogs in low temperature organic glasses was examined. From a mechanistic view-point, the compounds can be divided into three types: (i) those giving identical Hula-twist (HT) and one-bond-flip (OBF) products, (ii) those giving a single HT product that is different (hence distinguishable) from the OBF product and (iii) those showing two distinct HT processes but only one OBF process. Examples for all three types of analogs are provided emphasizing the most informative Type-II (stilbene analogs with identical but unsymmetrically substituted phenyl rings), including linear as well as conformationally constrained compounds. Conditions necessary for establishing HT and OBF processes are defined. Proper choice and design of model systems are essential for establishing or eliminating HT mechanism(s) of isomerization.

Study of alpha-crustacyanin utilizing halogenated canthaxanthins.

[structure: see text] The preparations and spectroscopic characteristics of five all-trans halogenated canthaxanthins are described in this letter. The air/light-sensitive halogenated canthaxanthins were used to study alpha-crustacyanin, a blue astaxanthin-protein complex, which is isolated from the carapace of the lobster. Steric and electronegative effects of the halogen substituents on the noncovalent interaction between astaxanthin and the protein in alpha-crustacyanin were observed.

Regioselective Hula-twist photoisomerization of cinnamate esters in organic glass.

Irradiation of ethyl cis-o-fluorocinnamate and related compounds in organic glass led to two HT-isomerization processes that exhibit a strong preference at C-beta than at C-alpha as shown by low temperature UV absorption spectroscopy and supported by ab initio calculations.

Conformational isomerizations of symmetrically substituted styrenes. No-reaction photoreactions by Hula-twist.

Symmetrically substituted styrenes photochemically gave unstable conformers in low temperature organic glass in a manner consistent with the recently postulated Hula-twist mechanism of photoisomerization.

Introduction to the symposium-in-print: photoisomerization pathways, torsional relaxation and the hula twists.

A review of recent literature on volume-conserving cis-trans photoisomerization reaction mechanism, including hula twist, is presented. Differences between substrates trapped in amorphous solids and chromophores that are protein bound are discussed.

Mechanistic pathways for the photoisomerization reaction of the anchored, tethered chromophore of the photoactive yellow protein and its mutants.

We show by way of physical organic reasoning that the currently known photochemical results of the chromophore of photoactive yellow protein (PYP) are consistent with that expected of a least volume-demanding process for an anchored, tethered chromophore. The primary photoreaction, interestingly, does not appear to involve a hula-twist process. However, the latter might be involved during subsequent transition of dark intermediates. Absorption data of intermediates obtained from a microsecond time-resolved spectroscopic study of three PYP mutants (E46Q, T50V and R52Q) are consistent with the above analyses.

The role of organic glasses in cis/trans photoisomerization at low temperatures.

Low temperature photoisomerization of stilbene and 1,4-diphenyl-1,3-butadiene derivatives was found to vary depending on the organic glass employed in such studies. Examination of the combined results showed that the variation was more likely to arise from the rigidity of the organic glass at the temperature of irradiation rather than the composition of the organic glass; that is, the observed results are consistent with the possible softening of the glass that surrounds the excited substrate in the same manner as detected in the photolysis of ethyl iodide reported by Porter and co-workers. These observations successfully account for the apparent "disagreement" of reports from the Hawaii and the Florida State groups on the mechanism of photoisomerization in low temperature glasses.

Nature of supramolecular complexes controlled by the structure of the guest molecules: formation of octa acid based capsuleplex and cavitandplex.

Factors that govern inclusion of organic molecules within octa acid (OA), a synthetic deep cavity cavitand, have been delineated by examining the complexation behavior of a number of organic molecules with varying dimensions and functionalities with OA. The formation of two types of complexes has been noted: the one which we call cavitandplex is a partially open complex in which a part of the guest molecule remains exposed to water, and the other termed capsuleplex is formed through assembly of two OA molecules. In capsuleplex, the guest is protected from water. Generally, guest molecules that possess ionic head groups form cavitandplex, and all others form capsuleplex. Capsuleplex may contain one or two guest molecules within the capsule. Small organic molecules (<10 A in length) may form both 2:1 and 2:2 capsuleplex, while longer ones (>12 A) preferentially form 2:1 capsuleplex. Extensive 1H NMR experiments have been carried out to characterize host-guest complexes. In the absence of the guest, OA tends to aggregate in water. The extent of aggregation depends on the concentration of OA and the presence of salts in solution. We expect the information obtained from this study to be of great value in predicting the nature of complexes with a given guest and facilitating appropriate guest chosen by researchers.

Possible role of the 11-cis-retinyl conformation in controlling the dual decay processes of excited rhodopsin.

In this work, we examine how the reported dual decay processes of rhodopsin and binding site stereospecificity can be accounted for by the recently available crystal structure of rhodopsin. Arguments are presented for possible presence of two rhodopsin "rotamers" that fit within the binding cavity. Directed pathways of decay could account for the observed excited decay processes. We summarize evidence for the possible existence of two different ground-state configurations that give rise to two different excited species.

Reflection on medium effects on photochemical reactivity.

In reexamining medium effects on photochemical reactions, we have emphasized those on unequilibrated excited species such as the Franck-Condon species. Despite recent advances in femtochemistry, such a discussion in molecular photochemistry is uncommon, and the problem remains challenging on account of the extremely short-lived excited species. However, in such cases, a small perturbation resulting from, for example, weak guest-host interactions could turn into a determining factor in dictating the course of a photochemical channel of deactivation. Examples of medium-directed diabatic processes have been examined with this idea in mind. A modified view on rhodopsin photoisomerization is presented along with the consideration that confinement does not necessarily lead to inhibition of reactions of the trapped substrate.

New aspects of diphenylbutadiene photochemistry. Regiospecific hula-twist photoisomerization.

In EPA glass at liquid nitrogen temperature, the E,E isomer of diphenylbutadiene (DPB) was photostable, while both the Z,E and Z,Z isomers underwent selective HT isomerization at center 1 giving the stable conformer of the double-bond isomerized trans product. That HT-1 was involved rather than the OBF process was shown by results of o,o'-dimethyl-DPB. Formation of unstable trans product corresponded to simultaneous configurational and conformational isomerization. The regioselectivity was found not sensitive to a substituent effect, as shown by the similar reactivity in p,p'- or o,o'-bistrifluoromethyl-DPB.

Steric effects in hula-twist photoisomerization. 1,4-dimethyl- and 2,3-dimethyl-1,4-diphenylbutadienes.

1,4-Dimethyl-1,4-diphenylbutadiene was shown to be able to execute regiospecific HT-1 photoisomerization around a methyl group when irradiated in a low-temperature organic glass, albeit at reduced efficiency. 2,3-Dimethyl-1,4-diphenylbutadiene exhibited a different type of steric effect, causing the E,E-isomer to undergo regiospecific HT-1 photoisomerization.

The molecular basis for the high photosensitivity of rhodopsin.

Based on structural information derived from the F NMR data of labeled rhodopsins, rhodopsin crystal structure, and excited-state properties of model polyenes, we propose a molecular mechanism that accounts specifically for the causes of the well-known enhanced photoreactivity of rhodopsin (increased rates and quantum yield of isomerization). It involves the key features of close proximity of C-187 to H-12 and chromophore bond lengthening upon light absorption. The resultant "sudden punch" to H-12 triggers dual processes of decay of the Franck-Condon-excited rhodopsin, a productive directed photoisomerization and a nonproductive decay returning to the ground state as two separate molecular pathways [based on real-time fluorescence results of Chosrowjan, H., Mataga, N., Shibata, Y., Tachibanaki, S., Kandori, H., Shichida, Y., Okada, T. & Kouyama, T. (1998) J. Am. Chem. Soc. 120, 9706-9707]. The two processes are controlled by the local protein structure: an empty space provided by the intradiscal loop connecting transmembrane helices 4 and 5 and a protein wall composed of amino acid units in transmembrane 3. Suggestions, involving retinal analogs and rhodopsin mutants, to improve the unusually high photosensitivity of rhodopsin are proposed.

Photochemical reactivity of polyenes: from dienes to rhodopsin, from microseconds to femtoseconds.

In reviewing the photochemistry of polyenes (from dienes and trienes to the visual retinyl chromophore), we categorize condensed-phase photochemical reactivity of molecules into two groups: those from thermally equilibrated excited species and those from unequilibrated excited species. Classical theories on radiationless transitions are useful for rationalizing the reactivity of molecules belonging to the first set only. The second group includes many of the exciting ultrafast photochemical reactions reported recently for polyenes (including dienes and trienes), in some cases with rates faster than vibrational relaxation. Much of the excited singlet-state reactions of polyenes, including the Hula-twist mechanism of photoisomerization, have been integrated with concepts introduced in other ultrafast spectroscopic/photochemical studies. Taking into consideration the special environment of the retinyl chromophore in rhodopsin, we propose a new mechanism for the phototrigger that accounts for its unusually fast rate of isomerization.