Properties of a flavonol-based photoCORM in aqueous buffered solutions: influence of metal ions, surfactants and proteins on visible light-induced CO release

Abstract

The properties of the extended flavonol 3-hydroxy-2-phenyl-benzo[g]chromen-4-one (2a) in DMSO : aqueous buffer solutions at pH ¼ 7.4, including in the presence of metal ions, surfactants and serum albumin proteins, have been examined. Absorption and emission spectral studies of 2a in 1 : 1 DMSO : PBS buffer (pH ¼ 7.4) indicate that a mixture of neutral and anionic forms of the flavonol are present. Notably, in 1 : 1 DMSO : TRIS buffer (pH ¼ 7.4) only the neutral form of the flavonol is present. These results indicate that the nature of the buffer influences the acid/base equilibrium properties of 2a. Introduction of a Zn(II) complex of 2a À to a 1 : 1 DMSO : aqueous buffer (TRIS or PBS, pH ¼ 7.4) solution produces absorption and emission spectral features consistent with the presence of a mixture of neutral 2a along with Zn(II)-coordinated or free 2a À . The nature of the anionic species present depends on the buffer composition. PBS buffered solutions (pH ¼ 7.4) containing the surfactants CTAB or SDS enable 2a to be solubilized at a much lower percentage of DMSO (3.3-4.0%). Solutions containing the cationic surfactant CTAB include a mixture of 2a and 2a À whereas only the neutral flavonol is present in SDScontaining buffered solution. Compound 2a is also solubilized in TRIS buffer solutions at low cocentrations of DMSO (3.3%, pH ¼ 7.4) in the presence of serum albumin proteins. Stern-Volmer analysis of the quenching of the inherent protein fluorescence indicates static binding of 2a to the proteins. The binding constant for this interaction is lower than that found for naturally-occurring flavonols (quercetin or morin) or 3-hydroxyflavone. Compound 2a binds to Site I of bovine and human serum albumin proteins as indicated by competition studies with warfarin and ibuprofen, as well as by docking investigations. The quantum yield for CO release from 2a (l irr ¼ 419 nm) under aqueous conditions ranges from 0.0006(3) when the compound is bound to bovine serum albumin to 0.017(1) when present as a zinc complex in a 1 : 1 DMSO : H 2 O solution. Overall, the results of these studies demonstrate that 2a is a predictable visible light-induced CO release compound under a variety of aqueous conditions, including in the presence of proteins. Scheme 2 Acid/base equilibrium of 2a.This journal is

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

“…Notably, 20 is best delivered to cells using bovine serum albumin (BSA) as a carrier protein. The binding constant for 20 to BSA is more than >900‐fold stronger than that of 19 , with both binding to the protein in a 1 : 1 stoichiometry ,. In the absence of visible light and in the presence of a physiologically relevant amount of BSA (0.6 mM) 20 exhibits no toxicity up to 100 μM in A549 cells whereas 19 is mildly toxic (IC 50 =82 μM).…”

“…This novel framework exhibits several advantageous features for the delivery of CO in biological environments. These include: (1) a clean, quantitative visible light‐driven CO release reaction that occurs in both protic and hydrophobic environments, and under atmospheric levels of O 2 (18 %) and hypoxic (1 % O 2 ) conditions;, (2) green fluorescence prior to CO release (Figure ) that enables monitoring of cellular uptake and distribution prior to CO release; and (3) a well‐defined, non‐toxic and non‐emissive organic by‐product (19, Figure ). Recently, 18 was also shown to undergo CO release using two‐photon excitation .…”

3-(4-Iodophenyl)-2,3-dihydro-1H-benzo[f]chromen-1-one

“…Traditional CORMS (carbon monoxide-releasing molecules) contain metal carbonyls whereas photoCORMS have recently become of interest because of their ability to release CO in biological systems. Our group is particularly interested in the extended flavonol motif as it has been shown to release CO quantitatively with visible light (Popova et al, 2017). Typically, we synthesize these flavonols in two steps from an acetyl naphthol and an aromatic aldehyde.…”

A bipyridine-ligated zinc(II) complex with bridging flavonolate ligation: synthesis, characterization, and visible-light-induced CO release reactivity

“…Radiopharmaceuticals (M = Re I ; Schutte et al, 2011) and light-induced CO releasing molecules (M = Zn II ; Grubel et al, 2011Grubel et al, , 2013 have also been developed based on metal-flavonolate structures. The 3-hydroxyflavonolate ligand typically coordinates in a bidentate Recently, we reported the first example of bridging flavonolate ligation in a dinuclear zinc complex using an extended flavonol ligand (Popova et al, 2017). In this contribution, we report the synthesis and characterization of a zinc-3-hydroxyflavonolate (3-Hfl) complex having the empirical formula [(bpy)Zn(3-Hfl)]ClO 4 (bpy is 2,2 0 -bipyridine), (1) (Scheme 2).…”