Current Research

Photoswitchable bioactive compounds: Photoactivation of drugs, enzymes, and other bio-molecules allows for achieving of the spatial and temporal control of their action. We design and synthesize compounds that are inactive in the dark but are converted into bioactive form upon irradiation with light of an appropriate wavelength. One of our goals is to overcome the most common drawback of caged biomolecules, which are known to release bioactive substrates in the dark due to conventional or enzymatic hydrolysis. The non-photochemical reactions of photoactivatable compounds (hydrolysis, thermal decomposition, etc.) that we develop are very slow and do not result in activation of the substrate.

Two-photon photochemistry: UV and visible light is efficiently absorbed by muscle tissues and only red and near infrared (NIR) radiation has sufficient depth of penetration in our bodies. Photons in this region, however, have relatively low energy, limiting the range of processes they can initiate. We are working on the development of the precursors that can be converted into an active form using nonresonant two-photon excitation. This approach allows us to use red/NIR light for photoactivation of UV-chromophores, while avoiding substrates sensitive to visible light, and therefore reducing accompanying phototoxicity.

Photolabile protecting groups, known as “cages” in biochemistry, allow for the spatial and temporal control of substrate release, as well as “reagentless” deprotection. Our group designs novel types of "safety-catch" photo-cages suitable for protection of broad range of organic molecules.

Mechanisms of light-induced reactions are investigated using state-of-the-art time-resolved IR (TIR) and UV-Vis (TUV) spectrometers. This data is then used in the design of novel photoswitchable bioactive compounds.

Photo-"click" reactions: Connection (or ligation) of two fragments to make a larger molecule or structure, as well as labeling DNA, proteins, and even whole cells, are usually achieved with the help of the so-called “click chemistry”. This term describe a set of bimolecular reactions that meet the following criteria: reactions should be wide in scope but selective, produce high yield of the product, proceed with reasonable rate under mild conditions, and tolerate broad range of solvents. We work on the development of light-induced ligation techniques, which proceeds under ambient conditions and does not require additional reagents or catalyst.

Selected Publications

Sutton, D. A. ; Yu, S. - H. ; Steet, R. ; Popik, V. V. Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking. Chem. Commun. 2016, 52, 553 - 556.
Brooks, K. ; Yatvin, J. ; McNitt, C. D. ; R. Reese, A. ; Jung, C. ; Popik, V. V. ; Locklin, J. Multifunctional Surface Manipulation Using Orthogonal Click Chemistry. Langmuir 2016, 32, 6600 - 6605.
Luo, W. ; Gobbo, P. ; McNitt, C. D. ; Sutton, D. A. ; Popik, V. V. ; Workentin, M. S. “Shine & Click” Photo-Induced Interfacial Unmasking of Strained Alkynes on Small Water-Soluble Gold Nanoparticles. Chemistry - A European Journal 2016.
Patel, J. M. ; Musa, M. M. ; Rodriguez, L. ; Sutton, D. A. ; Popik, V. V. ; Phillips, R. S. Mutation of Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase at Trp-110 affects stereoselectivity of aromatic ketone reduction. Organic & Biomolecular Chemistry 2014, 12, 5905.
Arnold, R. M. ; Patton, D. L. ; Popik, V. V. ; Locklin, J. A Dynamic Duo: Pairing Click Chemistry and Postpolymerization Modification To Design Complex Surfaces. Accounts of Chemical Research 2014, 140815135924000.
Nekongo, E. E. ; Popik, V. V. Photoactivatable Fluorescein Derivatives Caged with a (3-Hydroxy-2-naphthalenyl)methyl Group. The Journal of Organic Chemistry 2014, 79, 7665 - 7671.
Pathak, R. K. ; McNitt, C. D. ; Popik, V. V. ; Dhar, S. Copper-Free Click-Chemistry Platform to Functionalize Cisplatin Prodrugs. Chemistry - A European Journal 2014, 20, 6861 - 6865.
Hui, J. Zhe; Zaki, A. Al; Cheng, Z. ; Popik, V. ; Zhang, H. ; Prak, E. T. Luning; Tsourkas, A. Facile Method for the Site-Specific, Covalent Attachment of Full-Length IgG onto Nanoparticles. Small 2014, 10, 3354-3363.
Arumugam, S. ; Popik, V. V. Sequential “Click” – “Photo-Click” Cross-Linker for Catalyst-Free Ligation of Azide-Tagged Substrates. The Journal of Organic Chemistry 2014, 79, 2702 - 2708.
Arumugam, S. ; Guo, J. ; Mbua, N. Eric; Friscourt, F. ; Lin, N. ; Nekongo, E. ; Boons, G. - J. ; Popik, V. V. Selective and reversible photochemical derivatization of cysteine residues in peptides and proteins. Chemical Science 2014, 5, 1591.
Arumugam, S. ; Orski, S. V. ; Mbua, N. E. ; Boons, G. - J. ; Locklin, J. ; Popik, V. V. Photo-click chemistry strategies for spatiotemporal control of metal-free ligation, labeling, and surface derivatization. Pure and Applied Chemistry 2013, 85, 1513.
Warden-Rothman, R. ; Caturegli, I. ; Popik, V. ; Tsourkas, A. Sortase-Tag Expressed Protein Ligation: Combining Protein Purification and Site-Specific Bioconjugation into a Single Step. Analytical Chemistry 2013, 85, 11090 - 11097.
Elias, D. R. ; Poloukhtine, A. ; Popik, V. ; Tsourkas, A. Effect of ligand density, receptor density, and nanoparticle size on cell targeting. Nanomedicine: Nanotechnology, Biology and Medicine 2013, 9, 194 - 201.
Kulyashova, A. E. ; Sorokoumov, V. N. ; Popik, V. V. ; Balova, I. A. An acetylene zipper–Sonogashira reaction sequence for the efficient synthesis of conjugated arylalkadiynols. Tetrahedron Letters 2013, 54, 2235-2238.
Klán, P. ; Šolomek, T. ; Bochet, C. G. ; Blanc, A. ; Givens, R. ; Rubina, M. ; Popik, V. ; Kostikov, A. ; Wirz, J. Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chemical Reviews 2013, 113, 119-191.
Nekongo, E. E. ; Bagchi, P. ; Fahrni, C. ; Popik, V. 9-Aryl-9-Xanthenols: A Convenient Platform for the Design of Fluorimetric and Colorimetric pH Indicators. Organic & Biomolecular Chemistry 2012, 10, 9214-9218.
Orski, S. V. ; Sheppard, G. R. ; Arumugam, S. ; Arnold, R. M. ; Popik, V. V. ; Locklin, J. Rate Determination of Azide Click Reactions onto Alkyne Polymer Brush Scaffolds: A Comparison of Conventional and Catalyst-free Cycloadditions for Tunable Surface Modification. Langmuir 2012, 28, 14693-14702.
McNitt, C. ; Popik, V. Photochemical Generation of Oxa-Dibenzocyclooctyne (ODIBO) for Metal-Free Click Ligations. Organic & Biomolecular Chemistry 2012, 10, 8200-8202.
Arumugam, S. ; Popik, V. V. Attach, Remove, or Replace: Reversible Surface Functionalization Using Thiol-Quinone Methide Photoclick Chemistry. Journal of the American Chemical Society 2012, 134, 8408-8411.
Maitrani, C. ; Heyes, D. J. ; Hay, S. ; Arumugam, S. ; Popik, V. V. ; Phillips, R. S. Preparation and photophysical properties of a caged kynurenine. Bioorganic & Medicinal Chemistry Letters 2012, 22, 2737.
Arumugam, S. ; Popik, V. V. Bichromophoric fluorescent photolabile protecting group for alcohols and carboxylic acids. Photochemical & Photobiological Sciences 2012, 11, 518-521.
Yao, J. Z. ; Uttamapinant, C. ; Poloukhtine, A. A. ; Baskin, J. M. ; Codelli, J. A. ; Sletten, E. M. ; Bertozzi, C. R. ; Popik, V. V. ; Ting, A. Y. Fluorophore targeting to cellular proteins via enzyme-mediated azide ligation and strain-promoted cycloaddition. Journal of the American Chemical Society 2012, 134, 3720-3728.
Arumugam, S. ; Orski, S. V. ; Locklin, J. ; Popik, V. V. Photoreactive Polymer Brushes for High Density Surface Patterned Derivatization Using Diels-Alder Photo-click Reaction. Journal of the American Chemical Society 2012, 134, 179-182.
Bostic, H. E. ; Smith, M. D. ; Poloukhtine, A. A. ; Popik, V. V. ; Best, M. D. Membrane labeling and immobilization via copper-free click chemistry. Chemical Communications 2012, 48, 1431-1433.
Arumugam, S. ; Chin, J. ; Scirrmacher, R. ; Popik, V. V. ; Kostikov, A. P. [18F]Azadibenzocyclooctyne ([18F]ADIBO): A biocompatible radioactive labeling synthon for peptides using catalyst free [3+2] cycloaddition. Bioorganic & Medicinal Chemistry Letters 2011, 21, 6987-6991 .
Cheng, Z. ; Elias, D. R. ; Kamat, N. P. ; Johnston, E. ; Poloukhtine, A. A. ; Popik, V. V. ; Hammer, D. A. ; Tsourkas, A. Improved Tumor Targeting of Polymer-based Nanovesicles Using Polymer-Lipid Blends. Bioconjugate Chemistry 2011, 22, 2010-2029.
Arumugam, S. ; Popik, V. V. Patterned Surface Derivatization Using Diels–Alder Photoclick Reaction. Journal of the American Chemical Society 2011, 133, 15730-15736.
Arumugam, S. ; Popik, V. V. Light-Induced Hetero-Diels−Alder Cycloaddition: A Facile and Selective Photoclick Reaction. Journal of the American Chemical Society 2011, 133, 5573 - 5579.
Vinogradova, O. V. ; Balova, I. A. ; Popik, V. V. Synthesis and Reactivity of Cinnoline-Fused Cyclic Enediyne. The Journal of Organic Chemistry 2011, 76, 6937-6941.
Sanders, B. C. ; Friscourt, F. ; Ledin, P. A. ; Mbua, N. E. ; Arumugam, S. ; Guo, J. ; Boltje, T. J. ; Popik, V. V. ; Boons, G. - J. Metal-Free Sequential [3 + 2]-Dipolar Cycloadditions using Cyclooctynes and 1,3-Dipoles of Different Reactivity. Journal of the American Chemical Society 2011, 133, 949-957.
Sorokoumov, V. N. ; Popik, V. V. ; Balova, I. A. Access to 2,3-bis(buta-1,3-diynyl)pyridines. Mendeleev Commun. 2011, 21, 19-20.
Orski, S. V. ; Poloukhtine, A. A. ; Arumugam, S. ; Mao, L. ; Popik, V. V. ; Locklin, J. High density orthogonal surface immobilization via photoactivated copper-free click chemistry. Journal of the American Chemical Society 2010, 132, 11024 - 11026.
Polukhtine, A. ; Karpov, G. ; Pandithavidana, D. R. ; Kuzmin, A. ; Popik, V. V. Photochemical Triggering of the Bergman and Myers-Saito Cyclizations. Australian Journal of Chemistry 2010, 63, 1099 - 1107.
Kuzmin, A. ; Poloukhtine, A. ; Wolfert, M. A. ; Popik, V. V. Surface Functionalization Using Catalyst-Free Azide-Alkyne Cycloaddition. Bioconjugate Chemistry 2010, 21, 2076-2085.
Poloukhtine, A. ; Rassadin, V. ; Kuzmin, A. ; Popik, V. V. Nucleophilic Cycloaromatization of Ynamide-Terminated Enediynes. Journal of Organic Chemistry 2010, 75, 5953 - 5962.
Arumugam, S. ; Popik, V. V. Photochemical Generation and the Reactivity of o-Naphthoquinone Methides in Aqueous Solutions. Journal of the American Chemical Society 2009, 131, 11892 - 11899.
Kostikov, A. P. ; Malashikhina, N. ; Popik, V. V. Caging of Carbonyl Compounds as Photolabile (2,5-Dihydroxyphenyl)ethylene Glycol Acetals. Journal of Organic Chemistry 2009, 74, 1802 - 1804.
Pandithavidana, D. R. ; Poloukhtine, A. ; Popik, V. V. Photochemical Generation and Reversible Cycloaromatization of a Nine-Membered Ring Cyclic Enediyne. Journal of the American Chemical Society 2009, 131, 351 - 356.
Poloukhtine, A. A. ; Mbua, N. E. ; Wolfert, M. A. ; Boons, G. - J. ; Popik, V. V. Selective Labeling of Living Cells by a Photo-Triggered Click Reaction. Journal of the American Chemical Society 2009, 131, 15769 - 15776.
Kuzmin, A. V. ; Popik, V. V. Dual reactivity of a photochemically-generated cyclic enyne-allene. Chemical Communications (Cambridge, United Kingdom) 2009, 5707 - 5709.