Photodynamic therapeutics: basic principles and clinical applications.

The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA bases. We also discuss the role of DNA damage-tolerant DNA polymerases in UV lesion bypass and mutagenesis.

Mutations induced by ultraviolet light

Serendipity has long been a welcome yet elusive phenomenon in the advancement of chemistry. We sought to exploit serendipity as a means of rapidly identifying unanticipated chemical transformations. By using a high-throughput, automated workflow and evaluating a large number of random reactions, we have discovered a photoredox-catalyzed C–H arylation reaction for the construction of benzylic amines, an important structural motif within pharmaceutical compounds that is not readily accessed via simple substrates. The mechanism directly couples tertiary amines with cyanoaromatics by using mild and operationally trivial conditions.

Discovery of an α-Amino C–H Arylation Reaction Using the Strategy of Accelerated Serendipity

Photochemical reactions contribute in a significant way to the existing repertoire of carbon-carbon bond-forming reactions by allowing access to exceptional molecular structures that cannot be obtained by conventional means. In this Review, the most important photochemical transformations that have been employed in natural product synthesis are presented. Selected total syntheses are discussed as examples, with particular attention given to the photochemical key step and its stereoselectivity. The structural relationship between the photochemically generated molecule and the natural product is shown, and, where necessary, the consecutive reactions in the synthesis are illustrated and classified.

Photochemical reactions as key steps in natural product synthesis

The precise regulation of protein activity is fundamental to life. The allosteric control of an active site by a remote regulatory binding site is a mechanism of regulation found across protein classes, from enzymes to motors to signaling proteins. We describe a general approach for manipulating allosteric control using synthetic optical switches. Our strategy is exemplified by a ligand-gated ion channel of central importance in neuroscience, the ionotropic glutamate receptor (iGluR). Using structure-based design, we have modified its ubiquitous clamshell-type ligand-binding domain to develop a light-activated channel, which we call LiGluR. An agonist is covalently tethered to the protein through an azobenzene moiety, which functions as the optical switch. The agonist is reversibly presented to the binding site upon photoisomerization, initiating clamshell domain closure and concomitant channel gating. Photoswitching occurs on a millisecond timescale, with channel conductances that reflect the photostationary state of the azobenzene at a given wavelength. Our device has potential uses not only in biology but also in bioelectronics and nanotechnology.

https://www2.lbl.gov/Science-Articles/Archive/sabl/2007/Jun/LiGluR.pdf

Allosteric control of an ionotropic glutamate receptor with an optical switch.

Photochemistry Cis-Trans Isomerization of Alkenes, J. Saltiel, D.F. Sears, Jr., D.-H. Ko, and K.-M. Park Photorearrangement and Fragmentation of Alkenes, P.J. Kropp (2+2)-Cyclobutane Synthesis (Liquid Phase): Introduction and Mechanistic Consideration, G. Kaupp Cyclobutane Synthesis in the Solid Phase: Introduction and Mechanistic Considerations, G. Kaupp Photochemical Synthesis of Cage Compounds: Propellaprismanes and their Precursors, R. Gleiter and B. Treptow Copper(I) Catalyzed Intra- and Intermolecular Photocycloaddition Reactions of Alkenes, K. Langer and J. Mattay Photoreactions of Alkenes in Protic Media, P.J. Kropp The p-Cyclopropene Rearrangements, H.E. Zimmerman Diene/Cyclobutene Photochemistry, W.J. Leigh Photochemistry of Acyclic 1,3,5-Trienes and Related Compounds, W.H. Laarhoven and H.J.C. Jacobs Photochemistry of Vitamin D and Related Compounds, H.J.C. Jacobs and W.H. Laarhoven Photochemistry of Polyenes Related to Vitamin A, R.S.H. Liu Fulgides and Related Systems, H.G. Heller The Di-p-Methane Rearrangement, H.E. Zimmerman Photorearrangements of Benzobarrelenes and Related Analogues, C.-C. Liao and P.-H. Yang The Photochemistry of Dibenzobarrelene (9,10-Ethenoanthracene) and its Derivatives, J.R. Scheffer and J. Yang Valence Isomerization Between Norbornadiene and Quadricyclane Derivatives-A Solar Energy Storage Process, K. Maruyama and Y. Kubo Ring Isomerization of Benzene and Naphthalene Derivatives, A. Gilbert Phototransposition and Photo-Ring Contraction Reactions of 4-Pyrones and 4-Hydroxypyrylium Cations, J.W. Pavlik Photochemical Aromatic Substitution, J. Cornelisse Photochemical Reactions of Arenes with Amines, N.J. Bunce Intra- and Intermolecular Cycloadditions of Benzene Derivatives, P.A. Wender and T.M. Dore Cyclization of Stilbene and its Derivatives, A. Gilbert Ene Reactions with Singlet Oxygen, A.G. Griesbeck Photooxygenation of 1,3-Dienes, W. Adam and A.G. Griesbeck Photorearrangement of Endope roxides, J. Rigaudy Photochemical Methods for the Synthesis of 1,2-Dioxetanes, A.L. Baumstark and A. Rodriguez Oxidation of Aromatics, A. Albinia and M. Freccero Cyclobutane Photochemistry, K. Mizuno and C. Pac Photochemistry of Oxiranes - Photoreactions of Epoxynaphthoquinones, K. Maruyama and Y. Kubo Photodecarboxylation of Acids and Lactones, P. Wan and D. Budac The Photochemistry of Esters of Carboxylic Acids, J.A. Pincock Carbene Formation in the Photochemistry of Cyclic Ketones, S.M. Roberts Norrish Type I Processes of Ketones: Basic Concepts, C. Bohne Norrish Type I Processes of Ketones: Selected Examples and Synthetic Applications, C. Bohne Photoinduced Intermolecular Hydrogen Abstraction Reactions of Ketones, M. Rubin Hydrogen Abstraction Reactions of a-Diketones, M. Rubin Norrish Type II Photoelimination of Ketones: Cleavage of 1,4-Biradicals Formed by y-Hydrogen Abstraction, .J.-P. Wagner Norrish

Pill-Soon Song

Papers

CRC handbook of organic photochemistry and photobiology