September 11, 2018 at 1:38 pm

White Lab Develops Molecules to Deliver Carbon Monoxide and Singlet Oxygen to Cancer Cells Using Visible Light

Dr. Jessica White, portrait in office

Dr. Jessica White

The Jessica White Lab has prepared new transition metal complexes designed to both release multiple equivalents of carbon monoxide (CO) and generate singlet oxygen (1O2) when irradiated with visible light.

CO and 1O2 are both molecules that have been demonstrated to lead to cancer cell death, and the spatiotemporal delivery of these molecules using a visible light source could potentially provide a relatively noninvasive method for killing cancer cells and leaving healthy cells unharmed.

White is Assistant Professor of Chemistry & Biochemistry at Ohio University.

To date, few molecules have been reported to achieve the delivery of both CO and 1O2, and the impact of high levels of both molecules on cancer cells remains unknown. This article describes the synthesis, redox and photophysical properties, and the photochemical ligand dissociation reactions that occur when the metal complexes are exposed to visible light.

Their article, “Visible Light-Activated CO Release and 1O2 Photosensitizer Formation with Ru(II),Mn(I) Complexes,” was published in Inorganic Chemistry.

The lead author is Rachael Pickens in a third-year Ph.D. student in Chemistry & Biochemistry. The three contributing authors are OHIO undergraduates. Demi Reed (Forensic Chemistry) and Shanan Ashton (Biochemistry) are students who work in Jessica White’s lab, and Bertrand Neyhouse (Chemical Engineering) worked in Dr. Travis White’s lab until he graduated in Spring 2018.

Abstract: Two diimine-bridged Ru(II),Mn(I) complexes with a [(bpy)2Ru(BL)Mn(CO)3Br]2+ architecture, where bpy = 2,2′-bipyridine and BL = 2,3-bis(2-pyridyl)pyrazine (dpp; Ru(dpp)Mn) or 2,2′-bipyrimidine (bpm; Ru(bpm)Mn), were designed to both dissociate multiple equivalents of CO and produce 1O2 when irradiated with visible light. Analysis of the complexes by FTIR spectroscopy and cyclic voltammetry suggest a stronger π-accepting ability for bpm compared to dpp. Both complexes absorb light throughout the UV and visible regions with lowest energy absorption bands comprising overlapping Ru(dπ)→BL(π*) and Mn(dπ)→BL(π*) singlet metal-to-ligand charge transfer (1MLCT) and Br(p)→dpp(π*) singlet halide-to-ligand charge transfer (1XLCT) transitions. This lowest energy band is centered at 510 nm (ε = 12,000 M−1cm−1) for Ru(dpp)Mn and 553 nm (ε = 3,240 M−1cm−1) for Ru(bpm)Mn, and the absorption band extends to nearly 700 nm in each case. Irradiation with visible light (both 470 and 627 nm) releases all three CO ligands, as observed by a combination of UV-Vis, FTIR, and gas chromatography. The exchange of the first CO ligand with a solvent molecule occurs more efficiently for Ru(dpp)Mn470 = 0.22 ± 0.03  in H2O; 0.37 ± 0.06 in CH3CN) than Ru(bpm)Mn 470 = 0.049 ± 0.008 in H2O and 0.16 ± 0.03 in CH3CN), and the CO dissociation efficiency is unaffected by irradiation wavelength. The differences between Ru(dpp)Mn and Ru(bpm)Mn are proposed to result from the variation in electron density distribution across each formally reduced BL in the Mn(dπ)→BL(π*) 1MLCT excited state based on the nature of BL. Exhaustive photolysis causes the decomplexation of oxidized Mn(II), and the resulting [(bpy)2Ru(BL)]2+ complexes produce 1O2 with quantum yields (ΦΔ) of 0.37 ± 0.03 and 0.16 ± 0.01 for Ru(dpp) and Ru(bpm), respectively, with 460 nm irradiation. This bimetallic architecture presents the opportunity to use visible light to co-deliver both CO and 1O2, both of which have biological relevance in photoactivated therapeutics, with spatiotemporal control.


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