The importance of vitamin A in health research is self-evident. During the past grant periods, we completed the synthesis of all 16 possible geometric isomers. Now, for the first part of the current proposal, we propose to prepare isomers and analogs of vitamin A2 and the pro-vitamin A, Beta-carotene. The proposed methodologies continue to be a combination of regioselective photoisomerization and standard thermal reactions. Besides synthetic sequences using building block already available in this laboratory, we also propose new routes using the pre- assembled (commercially available) all-trans isomer of vitamin A or carotenoids for their conversion to the less available hindred isomers. Ensuing photochemical studies are proposed aiming at a better understanding of the general properties of excited polyenes. Such knowledge is clearly important for prediction of photochemistry of polyenes, for synthetic applications and for a better understanding of the specific mode of reaction in natural polyene containing systems. For the second part, we propose to study properties of several retinal binding proteins and caroteno-proteins. The emphasis for the first group will be on preparation of those retinoids known to give exceptionally red-shifted absorption characteristics. These compounds and the resultant pigment analogs will provide a set of chemical standard for determining the threshold energies necessary for visual excitation, proton or chloride pumping activities in bacteriorhodopsin or halorhodopsin and photomovement in sensory rhodopsin. The study of the carotenoproteins will involve the preparation of a series of carotenoids (oxygenated and fluorinated) analogs to study the corresponding protein analogs spectroscopically (uv-vis and NMR). Results are expected to be useful for the proposed Zagalsky model for Beta-crustacyanin, constructed by molecular modeling from retinol binding proteins because of lack of crystal structural data on carotenoproteins. Information from the proposed studies is expected to lead to a general understanding on the role of the protein host in perturbing the absorption characteristics and modes of reaction of any protein bound polyene systems, and to assist the design of other new red-shifted systems in other areas of studies (e.g., material science). The new sets of retinoids and carotenoids will not only be useful for our own studies but also for other biochemical and pharmaceutical researches.
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