Research
Ongoing Projects in the Cosa Group
Ongoing Projects in the Cosa Group
My research group designs and synthesises fluorogenic probes for the spatiotemporal imaging of reactive oxygen species in live cells. A number of applications to fundamental understanding of ROS in disease onset and towards new diagnostics are in progress. We are currently extending the use of this redox active probes to the chemical mapping of redox reactions not only on cells but also on nanomaterials, e.g. semiconductors, exploiting newly developed single molecule spectroelectrochemistry tools.
54) Godin, R.; Liu, H.-W.; Smith, L.; Cosa, G.; Dye Lipophilicity and Retention in Lipid Membranes: Implications for Single Molecule Spectroscopy. Langmuir, 30, 2014, 11138-11146
51) Godin, R.; Liu, H.-W.; Cosa, G. Ambient Condition Oxidation in Individual Liposomes Observed at the Single Molecule Level, Chem. Sci., 5, 2014, 2525-2529.
49) Krumova, K.; Greene, L, E.; Cosa, G. Fluorogenic a-Tocopherol Analogue for Monitoring the Antioxidant Status within the Inner Mitochondrial Membrane of Live Cells, J. Am. Chem. Soc., 135, 2013, 17135-17143.
41) Krumova, K.; Sayuri, F.; Cosa, G.; How Lipid Unsaturation, Peroxyl Radical Partitioning and Chromanol lipophilic Tail Affect the Antioxidant Activity of α-Tocopherol: Direct Visualization via High Throughput Fluorescence Studies Conducted with Fluorogenic α-Tocopherol Analogues, J. Am. Chem. Soc., 134, 2012, 10102-10113.
28) Khatchadourian, A.; Krumova, K.; Boridy, S.; Ngo, A. T.; Maysinger, D.; Cosa, G.; Molecular Imaging of Lipid-Peroxyl Radicals in Living Cells with a Bodipy-α-tocopherol Adduct, Biochemistry, 48, 2009, 5658 - 5668.
27) Krumova, K.; Oleynik, P.; Karam, P.; Cosa, G.; Phenol-based Lipophilic Fluorescent Antioxidant Indicators: a Rational Approach, J. Org. Chem., 74, 2009, 3641 - 3651.
22) Oleynik, P.; Ishihara, Y.; Cosa, G.; Design and Synthesis of a BODIPY-α-Tocopherol Adduct for Use as an Off/On Fluorescent Antioxidant Indicator, J. Am. Chem. Soc., 129, 2007, 1842-1843.
We work on the construction and single-molecule fluorescence study of hybrid lipid-conjugated polyelectrolyte nanostructures. The new structures provide a platform for fundamental photophysical studies on conjugated polyelectrolytes and towards developing biosensors.
68) Calver, C. F.; Schanze, K. S.; Cosa, G.; Biomimetic Light Harvesting Antenna Based on the Self-Assembly of Conjugated Polyelectrolytes Embedded within Lipid Membranes. ACS Nano, 10, 2016, 10598-10605.
59) Calver, C. F.; Liu, H.-W.; Cosa, G.; Exploiting Conjugated Polyelectrolyte Photophysics towards Monitoring Real-Time Lipid Membrane-Surface Interaction Dynamics at the Single Particle Level. Langmuir, 31, 2015, 11842-11850.
53) Karam, P.; Hariri, A.A.; Calver, C.F.; Zhao, X,; Schanze, K.S.; Cosa, G.; Interaction of Anionic Phenylene Ethynylene Polymers with lipids: from membrane embedding to liposome fusion. Langmuir, 30, 2014, 10704-10711.
35) Ngo, A. T.; Karam, P.; Cosa, G.; Conjugated polyelectrolyte-lipid interactions: Opportunities in biosensing (Invited review for the special issue "Perspectives and Challenges for the International Year of Chemistry"), Pure Appl. Chem. 83, 2011, 43-55.
33) Karam, P.; Ngo, A. T.; Rouiller, I.; Cosa, G.; Unraveling Electronic Energy Transfer in Single Conjugated Polyelectrolytes Encapsulated in Lipid Vesicles, Proc. Nat. Acad. Sci. USA, 107, 2010, 17480-17485.
A major thrust in our research group is to develop single molecule spectroscopy methods to assemble study and characterize DNA based nanomaterials. Work in collaboration with Prof. Sleiman of McGill, has demonstrated the assembly, single molecule fluorescence visualization and structural characterization of single DNA nanotubes of predesigned shapes.
62) Rahbani, J. F.; Hariri, A. A.; Cosa, G.; Sleiman, H. F.; Dynamic DNA Nanotubes: Reversible Switching between Single and Double-Stranded Forms, and Effect of Base Deletions ACS Nano, 9, 2015, 11898-11908.
56) Hariri, A. A.; Hamblin, G.; Gidi, Y.; Sleiman, H. F.; Cosa, G.; Stepwise Growth of Surface-grafted DNA Nanotubes Visualized at the Single Molecule Level. Nature Chem., 7, 2015, 295-300.
Our single molecule spectroscopy work extended single molecule fluorescence methodologies to mechanistic enzymatic studies on the activity of viral enzymes, involved in virus replication, in the presence and absence of inhibitors, providing a mechanism for enzymatic activity and drug inhibition.
50) Karam, P.; Powdrill, M. H.; Liu, H.-W.; Vasquez, C.; Mah, W.; Bernatchez, J.; Götte, M.; Cosa, G. Dynamics of HCV RNA-dependent RNA Polymerase NS5B in Complex with RNA, J. Biol. Chem., 289, 2014, 14399-14411.
67) Glembockyte, V.; Lin, J.; Cosa, G.; Improving the Photostability of Red- and Green-Emissive Single-Molecule Fluorophores via Ni2+ Mediated Excited Triplet-State Quenching. J. Phys. Chem. B, 120, 2016, 11923-11929.
55) Glembockyte, V.; Lincoln, R.; Cosa, G.; Cy3 Photoprotection Mediated by Ni2+ for Extended Single-Molecule Imaging: Old Tricks for New Techniques. J. Am. Chem. Soc., 137, 2015, 1116-1122.
57) Lincoln, R.; Greene, L.; Bain, C.; Flores-Rizo, J. O.; Bohle, D. S.; Cosa, G.; When Push Comes to Shove: Unravelling the Mechanism and Scope of Non-emissive meso-Unsaturated BODPY dyes. J. Phys. Chem. B, 119, 2015, 4758-4765.
52) Lincoln, R.; Greene, L. E.; Krumova, K..; Ding, Z.; Cosa, G.; Electronic Excited State Redox Properties for BODIPY Dyes Predicted from Hammett Constants: Estimating the Driving Force of Photoinduced Electron Transfer, J. Phys. Chem. A, 118, 2014, 10622-10630
61) Godin, R.; Sherman, B.; Bergkamp, J.; Chesta, C., A.; Moore, A.; Moore, T; Palacios, R. E.; Cosa, G.; Charge Transfer Dynamics of Fluorescent Dye-Sensitized Electrodes under Applied Biases. J. Phys. Chem. Lett., 6, 2015, 2688-2693.
58) Godin, R.; Palacios, R.; Cosa, G.; Heterogeneous Charge Mobility in Individual Conjugated Polyelectrolyte Nanoparticles Revealed by Two-Color Single Particle Spectroelectrochemistry Studies. J. Phys. Chem. C, 119, 2015, 12875-12886.
63) Durantini, A.; Greene, L. E.; Lincoln, R.; Martinez, S.; Cosa, G.; Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy. J. Am. Chem. Soc., 138, 2016, 1215-1225.