Wonwoo Nam

Fluorescent zinc sensor with minimized proton-induced interferences: photophysical mechanism for fluorescence turn-on response and detection of endogenous free zinc ions.

A new fluorescent zinc sensor (HNBO-DPA) consisting of 2-(2-hydroxy-3-naphthyl)benzoxazole (HNBO) chromophore and a di(2-picolyl)amine (DPA) metal chelator has been prepared and examined for zinc bioimaging. The probe exhibits zinc-induced fluorescence turn-on without any spectral shifts. Its crystal structure reveals that HNBO-DPA binds a zinc ion in a pentacoordinative fashion through the DPA and HNBO moieties. Steady-state photophysical studies establish zinc-induced deprotonation of the HNBO group. Nanosecond and femtosecond laser flash photolysis and electrochemical measurements provide evidence for zinc-induced modulation of photoinduced electron transfer (PeT) from DPA to HNBO. Thus, the zinc-responsive fluorescence turn-on is attributed to suppression of PeT exerted by deprotonation of HNBO and occupation of the electron pair of DPA, a conclusion that is further supported by density functional theory and time-dependent density functional theory (DFT/TD-DFT) calculations. Under physiological conditions (pH 7.0), the probe displays a 44-fold fluorescence turn-on in response to zinc ions with a K(d) value of 12 pM. The fluorescent response of the probe to zinc ions is conserved over a broad pH range with its excellent selectivity for zinc ions among biologically relevant metal ions. In particular, its sensing ability is not altered by divalent transition metal ions such as Fe(II), Cu(II), Cd(II), and Hg(II). Cell experiments using HNBO-DPA show its suitability for monitoring intracellular zinc ions. We have also demonstrated applicability of the probe to visualize intact zinc ions released from cells that undergo apoptosis. More interestingly, zinc-rich pools in zebrafish embryos are traced with HNBO-DPA during early developmental stages. The results obtained from the in vitro and in vivo imaging studies demonstrate the practical usefulness of the probe to detect zinc ions.

Proton-Promoted Oxygen Atom Transfer vs Proton-Coupled Electron Transfer of a Non-Heme Iron(IV)-Oxo Complex

Sulfoxidation of thioanisoles by a non-heme iron(IV)-oxo complex, [(N4Py)Fe(IV)(O)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), was remarkably enhanced by perchloric acid (70% HClO(4)). The observed second-order rate constant (k(obs)) of sulfoxidation of thioaniosoles by [(N4Py)Fe(IV)(O)](2+) increases linearly with increasing concentration of HClO(4) (70%) in acetonitrile (MeCN)at 298 K. In contrast to sulfoxidation of thioanisoles by [(N4Py)Fe(IV)(O)](2+), the observed second-order rate constant (k(et)) of electron transfer from one-electron reductants such as [Fe(II)(Me(2)bpy)(3)](2+) (Me(2)bpy = 4,4-dimehtyl-2,2-bipyridine) to [(N4Py)Fe(IV)(O)](2+) increases with increasing concentration of HClO(4), exhibiting second-order dependence on HClO(4) concentration. This indicates that the proton-coupled electron transfer (PCET) involves two protons associated with electron transfer from [Fe(II)(Me(2)bpy)(3)](2+) to [(N4Py)Fe(IV)(O)](2+) to yield [Fe(III)(Me(2)bpy)(3)](3+) and [(N4Py)Fe(III)(OH(2))](3+). The one-electron reduction potential (E(red)) of [(N4Py)Fe(IV)(O)](2+) in the presence of 10 mM HClO(4) (70%) in MeCN is determined to be 1.43 V vs SCE. A plot of E(red) vs log[HClO(4)] also indicates involvement of two protons in the PCET reduction of [(N4Py)Fe(IV)(O)](2+). The PCET driving force dependence of log k(et) is fitted in light of the Marcus theory of outer-sphere electron transfer to afford the reorganization of PCET (λ = 2.74 eV). The comparison of the k(obs) values of acid-promoted sulfoxidation of thioanisoles by [(N4Py)Fe(IV)(O)](2+) with the k(et) values of PCET from one-electron reductants to [(N4Py)Fe(IV)(O)](2+) at the same PCET driving force reveals that the acid-promoted sulfoxidation proceeds by one-step oxygen atom transfer from [(N4Py)Fe(IV)(O)](2+) to thioanisoles rather than outer-sphere PCET.

Dioxygen Activation by a Non-Heme Iron(II) Complex: Theoretical Study toward Understanding Ferric-Superoxo Complexes.

We present a systematic study using density functional theory (DFT) and coupled cluster (CCSD(T)) computations with an aim of characterizing a non-heme ferric-superoxo complex [(TMC)Fe(O2)](2+) (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) that was proposed to perform allylic C-H activation of cyclohexene (Lee, Y.-M. et al. J. Am. Chem. Soc.2010, 132, 10668). As such, we investigated a series of iron-O2 species without and with a sixth ligand bound to the iron ion in different O2 coordination modes (end-on and side-on) and different spin states. Most of the iron-O2 complexes were found to be iron(III)-superoxo species, Fe(III)(O2(-)), with high-spin (S = 5/2) or intermediate-spin (S = 3/2) ferric centers coupled ferromagnetically or antiferromagnetically to the superoxide anion radical. One iron(IV)-peroxo state, Fe(IV)(O2(2-)), was also examined. The preference for ferromagnetic or antiferromagnetic coupling modes between the superoxo and ferric radicals was found to depend on the FeOO angle, where a side-on tilt favors ferromagnetic coupling whereas the end-on tilt favors antiferromagnetic states. Experimental findings, e.g., the effects of solvent, spin state, and redox potential of non-heme Fe(II) complexes on O2 activation, were corroborated in this work. Solvent effects were found to disfavor O2 binding, relative to the unbound ferrous ion and O2. The potential H-abstraction reactivity of the iron(III)-superoxo species was considered in light of the recently proposed exchange-enhanced reactivity principle (Shaik, S.; Chen, H.; Janardanan, D. Nat. Chem.2011, 3, 19). It is concluded that localization and/or decoupling of an unpaired electron in the d-block of high-spin Fe(III) center in the S = 2 and 3 ferric-superoxo complexes during H abstractions enhances exchange stabilization and may be the root cause of the observed reactivity of [(TMC)Fe(O2)](2+).

A chromium(III)-superoxo complex in oxygen atom transfer reactions as a chemical model of cysteine dioxygenase.

Metal-superoxo species are believed to play key roles in oxygenation reactions by metalloenzymes. One example is cysteine dioxygenase (CDO) that catalyzes the oxidation of cysteine with O(2), and an iron(III)-superoxo species is proposed as an intermediate that effects the sulfoxidation reaction. We now report the first biomimetic example showing that a chromium(III)-superoxo complex bearing a macrocyclic TMC ligand, [Cr(III)(O(2))(TMC)(Cl)](+), is an active oxidant in oxygen atom transfer (OAT) reactions, such as the oxidation of phosphine and sulfides. The electrophilic character of the Cr(III)-superoxo complex is demonstrated unambiguously in the sulfoxidation of para-substituted thioanisoles. A Cr(IV)-oxo complex, [Cr(IV)(O)(TMC)(Cl)](+), formed in the OAT reactions by the chromium(III)-superoxo complex, is characterized by X-ray crystallography and various spectroscopic methods. The present results support the proposed oxidant and mechanism in CDO, such as an iron(III)-superoxo species is an active oxidant that attacks the sulfur atom of the cysteine ligand by the terminal oxygen atom of the superoxo group, followed by the formation of a sulfoxide and an iron(IV)-oxo species via an O-O bond cleavage.

Photoelectrocatalysis to Improve Cycloreversion Quantum Yields of Photochromic Dithienylethene Compounds

An open and shut case: photoirradiation of the 9-mesityl-10-methylacridinium ion, which acts as a photoredox catalyst, evoked catalytic cycloreversion of the photochromic 1,2-dithienylethene (DTE) compounds with one order of magnitude enhancement in quantum yields. Mechanistic studies revealed that the back electron transfer and electron transfer from the neutral closed form of DTE compounds to the open-form radical cation are key steps.

Double Action: Toward Phosphorescence Ratiometric Sensing of Chromium Ion

The phosphorescence double ratiometric sensor detects Cr(III) ions by taking advantage of reversible coordination binding and the biomimetic oxidation reaction.

Mechanism and Fluorescence Application of Electrochromism in Photochromic Dithienylcyclopentene

The kinetic process of key intermediates involved in the electrochemical ring opening of photochromic dithienylcyclopentenes (DTEs) has been observed for the first time, where the electronic nature of the DTEs is an important factor that determines the rate-determining step in the electrochromism. The dual chromic property has been implemented to a single molecular fluorescence memory.

Fluorescence ratiometric zinc sensors based on controlled energy transfer

The high-fidelity detection of labile zinc is of central importance for understanding the molecular mechanisms that link zinc homeostasis and human pathophysiology. Fluorescence ratiometric sensors are most suitable for the detection and trafficking of intracellular zinc ions. Here, we report the development of fluorescence ratiometric zinc sensors (HN1 and HN2) based on two-fluorophore platforms. The sensor constructs include blue fluorescent umbelliferone and an energy-accepting chromophore that absorbs the blue fluorescence. Zinc binding was found to promote fluorescence turn-on of the umbelliferone emission by suppression of intramolecular photoinduced electron transfer, thereby facilitating resonance energy transfer to the energy acceptors. The net observables were the fluorescence ratiometric changes, the extent of which depended strongly on the chemical structures of the acceptors. Photophysical investigations, including steady-state and transient photoluminescence spectroscopy, suggested a mechanism for the fluorescent zinc response that involved a combination of the intramolecular electron transfer and the interchromophoric energy transfer. The zinc probes displayed sensing capability that is suitable for the detection of biological zinc ions, with good selectivity, pH tolerance, and appropriate Kd values. Finally, zinc detection was demonstrated by fluorescence ratiometric visualization of exogenously supplied zinc ions in live HeLa cells. The probes enabled the reliable monitoring of zinc equilibration across the cell membrane.

Predictive studies of H-atom abstraction reactions by an iron(IV)–oxo corrole cation radical oxidant

Density functional theory calculations compare the reactivity of iron(IV)-oxo porphyrin and corrole cation radical species in H-atom abstraction reactions.