Selective and Sensitive Superoxide Detection with a New <i>Diselenide</i>-Based Molecular Probe in Living Breast Cancer Cells

Manjare, Sudesh T.,Kim, Sungsoo,Heo, Won Do,Churchill, David G. American Chemical Society 2014 Organic letters Vol.16 No.2

<P>A diselenide-based BODIPY probe was prepared; it was found to be sensitive and selective for superoxide in giving [-Se(O)Se(O)-] oxidation. Probing was reversible through the use of biothiols; <SUP>77</SUP>Se NMR and other types of spectroscopy were employed. Practical medicinal utility was demonstrated in MCF-7/ADR cancer cells.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2014/orlef7.2014.16.issue-2/ol4033013/production/images/medium/ol-2013-033013_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol4033013'>ACS Electronic Supporting Info</A></P>

Selenium- and Tellurium-Containing Fluorescent Molecular Probes for the Detection of Biologically Important Analytes

Manjare, Sudesh T.,Kim, Youngsam,Churchill, David G. American Chemical Society 2014 Accounts of chemical research Vol.47 No.10

<title>Conspectus</title><P>As scientists in recent decades have discovered, selenium is an important trace element in life. The element is now known to play an important role in biology as an enzymatic antioxidant. In this case, it sits at the active site and converts biological hydrogen peroxides to water. Mimicking this reaction, chemists have synthesized several organoselenium compounds that undergo redox transformations. As such, these types of compounds are important in the future of both medicinal and materials chemistry. One main challenge for organochalcogen chemists has been to synthesize molecular probes that are soluble in water where a selenium or tellurium center can best modify electronics of the molecule based on a chemical oxidation or reduction event.</P><P>In this Account, we discuss chemists’ recent efforts to create chalcogen-based chemosensors through synthetic means and current photophysical understanding. Our work has focused on small chromophoric or fluorophoric molecules, in which we incorporate discrete organochalcogen atoms (e.g., R-Se-R, R-Te-R) in predesigned sites. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively oxidize compounds and to study the level of analyte selectivity by way of their optical responses. All the reports we discussed here deal with <I>well-defined and small synthetic</I> molecular systems.</P><P>With a large number of reports published over the last few years, many have notably originated from the laboratory of K. Han (P. R. China). This growing body of research has given chemists new ideas for the previously untenable reversible reactive oxygen species detection. While reversibility of the probe is technically important from the stand-point of the chalcogen center, facile regenerability of the probe using a secondary analyte to recover the initial probe is a very promising avenue. This is because (bio)chalcogen chemistry is extremely rich and bioinspired and continues to yield important developments across many scientific fields. Organochalcogen (R-E-R) chemistry in such chemical recognition and supramolecular pursuits is a fundamental tool to allow chemists to explore stable organic-based probe modalities of interest to develop better spectroscopic tools for (neuro)biological applications.</P><P>Chalcogen donor sites also provide sites where metals can coordinate, and facile oxidation may extend to the sulfone analogues (R-EO<SUB>2</SUB>-R) or beyond. Consequently, chemists can then make use of reliable reversible chemical probing platforms based on the chemical redox properties valence state switching principally from 2 to 4 (and back to 2) of selenium and tellurium atoms. The main organic molecular skeletons have involved chemical frames including boron-dipyrromethene (BODIPY) systems, extended cyanine groups, naphthalimide, rhodamine, and fluorescein cores, and isoselenazolone, pyrene, coumarin, benzoselenadiazole, and selenoguanine systems.</P><P>Our group has tested many such molecular probe systems in cellular milieu and under a series of conditions and competitive environments. We have found that the most important analytes have been reactive oxygen species (ROS) such as superoxide and hypochlorite. Reactive nitrogen species (RNS) such as peroxynitrite are also potential targets. In addition, we have also considered Fenton chemistry systems. Our research and that of others shows that the action of ROS is often reversible with H<SUB>2</SUB>S or biothiols such as glutathione (GSH).</P><P>We have also found that a second class of analytes are the thiols (RSH), in particular, biothiols. Here, the target group might involve an R-Se-Se-R group. The study of analytes also extends to metal ions, for example, Hg<SUP>2+</SUP>, and anions such as fluoride (F<SUP>–</SUP>), and we have developed NIR-based systems as well. These work through various photomechanisms, including photoinduced electron transfer (PET), twisted i

Facile <i>meso</i>-BODIPY Annulation and Selective Sensing of Hypochlorite in Water

Manjare, Sudesh T.,Kim, Jin,Lee, Yunho,Churchill, David G. American Chemical Society 2014 Organic letters Vol.16 No.2

<P>Annulated BODIPY chalcogenide (Se, Te) systems were synthesized from their respective bis(<I>o</I>-formylphenyl)dichalcogenide intermediates. The annulated BODIPY selenide product was confirmed by X-ray diffraction. The red-shifted telluride version was found to be sensitive and selective for hypochlorite detection, reversible upon treatment with biothiols.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2014/orlef7.2014.16.issue-2/ol403405n/production/images/medium/ol-2013-03405n_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol403405n'>ACS Electronic Supporting Info</A></P>

Novel Reversible Zn²⁺-Assisted Biological Phosphate “Turn-On” Probing through Stable Aryl-hydrazone Salicylaldimine Conjugation That Attenuates Ligand Hydrolysis

Tsay, Olga G.,Manjare, Sudesh T.,Kim, Hyungjun,Lee, Kang Mun,Lee, Yoon Sup,Churchill, David G. American Chemical Society 2013 Inorganic Chemistry Vol.52 No.17

<P>A novel reversible zinc(II) chemosensing ensemble (<B>2</B>·Zn<SUP>2+</SUP>) allows for selective “turn-on” fluorescence sensing of ATP and PPi in aqueous media (detection limits: 2.4 and 1.0 μM, respectively) giving selective binding patterns: ATP ∼ PPi > ADP ≫ AMP > monophosphates ≈ remaining ions tested. The conjugated hydrazone [CN<I>NH</I>R] resists hydrolysis considerably, compared to the imine [CN<I>CH</I><SUB><I>2</I></SUB>R, pyridin-2-ylmethanamine] functionality, and generalizes to other chemosensing efforts. Prerequisite Zn<SUP>2+</SUP>·[O<SUB>phenol</SUB>N<SUB>imine</SUB>N<SUB>pyr</SUB>] binding is selective, as determined by UV–vis and NMR spectroscopy; ATP or PPi extracts Zn<SUP>2+</SUP> to regenerate the ligand–fluorophore conjugate (PPi: turn-on, 512 nm; detection limit, 1.0 μM). Crystallography, 2-D NMR spectroscopy, and DFT determinations (B3LYP/631g*) support the nature of compound <B>2</B>. 2-Hydrazinyl-pyridine-salicylaldehyde conjugation is unknown, as such; a paucity of chemosensing-Zn<SUP>2+</SUP> binding reports underscores the novelty of this modifiable dual cation/anion detection platform. A combined theoretical and experimental approach reported here allows us to determine both the potential uniqueness as well as drawbacks of this novel conjugation.</P><P>A chemosensing ensemble, involving conjugated hydrazone [CN<I>NH</I>R], greatly resists hydrolysis to allow for reversible and selective “turn-on” fluorescence sensing of ATP and PPi in aqueous media: ATP ∼ PPi > ADP ≫ AMP > monophosphates ≈ others.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/inocaj/2013/inocaj.2013.52.issue-17/ic4013526/production/images/medium/ic-2013-013526_0011.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ic4013526'>ACS Electronic Supporting Info</A></P>

Solvent-controlled Novel Cu+ and Cu+/2+ Fluorescent “Turn-ON” Probing

하용황,Dhiraj P. Murale,Sudesh T. Manjare,Minseong Kim,Jeong A. Jeong,처칠 대한화학회 2016 Bulletin of the Korean Chemical Society Vol.37 No.1

A novel Schiff base probe, carbamoyl salicylimine benzothiazole hydrazine, was prepared and measured for its probing ability. High sensitivity was shown for Cu+ and Cu2+. When solvent polarity was regulated through a combination of H2O and acetonitrile, selective sensing of Cu+ or the total amount of Cu+ and Cu2+ was possible. In addition, a linear hypsochromic fluorescent shift of about 30 nm was shown. A binding stoichiometry of 1:1 exists at low concentration. Time-dependent emission measurement showed an exponential decay curve (τ1 = 2.99 × 103 s, 10 equiv of Cu+) and a linear decay line (slope = –0.0216, 5 equiv of Cu+). Interference experiments in 50% acetonitrile in H2O showed that the emission produced by Cu+ and Cu2+ was not disturbed by other metal ions or by acidity or basicity. Peroxynitrite changed the emission trends; Cu+ emission decreased (78%) and Cu2+ fluorescence increased (28-fold). Biothiols, l-cysteine, dl-homocysteine, reduced glutathione, and N-acetyl-l-cysteine affected the complete reversibility of Cu+-induced emission in 50% (v/v) acetonitrile in H2O, relative to partial reversibility of Cu2+ emission. Thus, by regulating the ratio between acetonitrile and H2O, Cu+ and Cu+/2+ can be probed selectively.

Fluorescence probing of the ferric Fenton reaction <i>via</i> novel chelation

Murale, Dhiraj P.,Manjare, Sudesh T.,Lee, Yoon-Sup,Churchill, David G. The Royal Society of Chemistry 2014 Chemical communications Vol.50 No.3

<P>A new probe-chelator PET dyad was synthesised, which can be used to detect Fe<SUP>3+</SUP><I>via</I> fluorescence enhancement to discriminate between Fe<SUP>2+</SUP> and Fe<SUP>3+</SUP><I>via</I> Fenton chemistry involving hydrogen peroxide. This is the first BODIPY which works as a 2 : 1 multiplexer for Fe<SUP>3+</SUP>, Fe<SUP>2+</SUP> and H<SUB>2</SUB>O<SUB>2</SUB>.</P> <P>Graphic Abstract</P><P>A new probe-chelator PET dyad was synthesised, which can be used to detect Fe<SUP>3+</SUP><I>via</I> fluorescence enhancement to discriminate between Fe<SUP>2+</SUP> and Fe<SUP>3+</SUP><I>via</I> Fenton chemistry involving hydrogen peroxide. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc47038e'> </P>

H⁺-Assisted fluorescent differentiation of Cu⁺ and Cu²⁺: effect of Al³⁺-induced acidity on chemical sensing and generation of two novel and independent logic gating pathways

Ha, Yonghwang,Murale, Dhiraj P.,Yun, Changsuk,Manjare, Sudesh T.,Kim, Hyungjun,Kwak, Juhyoun,Lee, Yoon Sup,Churchill, David G. The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.29

<P>A novel Schiff base probe exhibited strong ‘turn-ON’ fluorescence for Cu<SUP>2+</SUP> at 345 nm, Al<SUP>3+</SUP> at 445 nm, and Cu<SUP>+</SUP> at 360 nm in the presence of Al<SUP>3+</SUP> in organic solvent (acetonitrile), which allowed for construction of molecular logic gates ‘INH’ and ‘1:2 DEMULTIPLEXING.’ H<SUP>+</SUP> generated from Al<SUP>3+</SUP> contributed greatly to Cu<SUP>+</SUP> chemosensing based on a redox non-innocence mechanism.</P> <P>Graphic Abstract</P><P>A novel logic gate containing protecting groups interacts with various species (acetonitrile) with fluorescence responses relating to ligand non innocence. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc10025e'> </P>

Novel intramolecular π–π-interaction in a BODIPY system by oxidation of a single selenium center: geometrical stamping and spectroscopic and spectrometric distinctions

Kim, Youngsam,Jun, Taehong,Mulay, Sandip V.,Manjare, Sudesh T.,Kwak, Jinseong,Lee, Yunho,Churchill, David G. The Royal Society of Chemistry 2017 Dalton Transactions Vol.46 No.12

<▼1><P>A reversible fluorescent OFF–ON system displaying a novel <I>intramolecular</I> π–π interaction has been discovered and exploited for hypochlorite chemosensing.</P></▼1><▼2><P>A new BODIPY system displaying an intramolecular π–π-interaction was synthesized and studied. When the selenium center was oxidized, the substituted phenyl group undergoes π–π stacking with one side of the BODIPY core. The oxidized form showed, not only a down-field shift in the NMR peak, but also splitting due to geometrical changes that arise when going from <I>C</I>s to <I>C</I>1. The compound was characterized by X-ray diffraction; DFT methods helped elucidate the influence of the unexpected π–π stack and its connection to the photophysical properties imparted by the Se oxidation.</P></▼2>