A Pyrrolyl-Based Triazolophane: A Macrocyclic Receptor With CH and NH Donor Groups That Exhibits a Preference for Pyrophosphate Anions

Sessler, Jonathan L.,Cai, Jiajia,Gong, Han-Yuan,Yang, Xiaoping,Arambula, Jonathan F.,Hay, Benjamin P. American Chemical Society 2010 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.132 No.40

<P>A pyrrolyl-based triazolophane, incorporating CH and NH donor groups, acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO<SUB>4</SUB><SUP>−</SUP> > H<SUB>2</SUB>PO<SUB>4</SUB><SUP>−</SUP> > Cl<SUP>−</SUP> > Br<SUP>−</SUP> (all as the corresponding tetrabutylammonium salts), with NH−anion interactions being more important than CH−anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot <I>via</I> NH and CH hydrogen bonds.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2010/jacsat.2010.132.issue-40/ja107098r/production/images/medium/ja-2010-07098r_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja107098r'>ACS Electronic Supporting Info</A></P>

Ion pair receptors

Kim, Sung Kuk,Sessler, Jonathan L. Royal Society of Chemistry 2010 Chemical Society reviews Vol.39 No.10

<P>Compared with simple ion receptors, which are able to bind either a cation or an anion, ion pair receptors bearing both a cation and an anion recognition site offer the promise of binding ion pairs or pairs of ions strongly as the result of direct or indirect cooperative interactions between co-bound ions. This critical review focuses on the recent progress in the design of ion pair receptors and summarizes the various binding modes that have been used to accommodate ion pairs (110 references).</P>

Tetrathiafulvalene (TTF)-Annulated Calix[4]pyrroles: Chemically Switchable Systems with Encodable Allosteric Recognition and Logic Gate Functions

Park, Jung Su,Sessler, Jonathan L. American Chemical Society 2018 Accounts of chemical research Vol.51 No.10

<P><B>Conspectus</B></P><P>Molecular and supramolecular systems capable of switching between two or more states as the result of an applied chemical stimulus are attracting ever-increasing attention. They have seen wide application in the development of functional materials including, but not limited to, molecular and supramolecular switches, chemosensors, electronics, optoelectronics, and logic gates. A wide range of chemical stimuli have been used to control the switching within bi- and multiple state systems made up from either singular molecular entities or supramolecular ensembles. In general, chemically triggered switching systems contain at least two major functional components that provide for molecular recognition and signal transduction, respectively. These components can be connected to one another via either covalent or noncovalent linkages.</P><P>Of particular interest are switchable systems displaying cooperative or allosteric features. Such advanced control over function is ubiquitous in nature and, in the case of synthetic systems, may allow the capture and release of a targeted chemical entity or permit the transduction of binding information from one recognition site to another. Allosterically controlled complexation and decomplexation could also permit the amplification or deamplification of analyte-specific binding affinity, lead to nonlinear binding characteristics, or permit a magnification of output signals.</P><P>Our own efforts to develop chemically driven supramolecular switches, advanced logic gates, and multifunction cascade systems have focused on the use of tetrathiafulvalene (TTF) annulated calix[4]pyrroles (C4Ps). These systems, TTF-C4Ps, combine several orthogonal binding motifs within what are conformationally switchable receptor frameworks. Their basic structure and host-guest recognition functions can be controlled via application of an appropriate chemical stimulus. Homotropic or heterotropic allosteric molecular recognition behavior is often seen. This has allowed us to (1) produce self-assembled structures, (2) control switching between bi- and multistate constructs, (3) generate chemical logic gates performing chemical-based Boolean logic operations, (4) create ionically controlled three-state logic systems that release different chemical messengers and activate disparate downstream reactions, and (5) encode a variety advanced functional operations into what are relatively simple molecular-scale devices.</P><P>Looking to the future, we believe that exploiting allosteric control will expand opportunities for supramolecular chemists and allow some of the complexity seen in biology to be reproduced in simple constructs. Of particular appeal would be a capacity to release chemical messengers at will, perhaps after a prior capture and chemical modification step, that then encode for further downstream functions as seen in the case of the small molecules, such as neurotransmitters and pheromones, used by nature for the purpose of intraentity communication. Molecular scale logic devices with allosteric functions are thus the potential vanguard of a new area of study involving interactions between multiple discrete components with an emphasis on functional outcomes.</P> [FIG OMISSION]</BR>

Modern reaction-based indicator systems

Cho, Dong-Gyu,Sessler, Jonathan L. Royal Society of Chemistry 2009 Chemical Society reviews Vol.38 No.6

<P>Traditional analyte-specific synthetic receptors or sensors have been developed on the basis of supramolecular interactions (<I>e.g.</I>, hydrogen bonding, electrostatics, weak coordinative bonds). Unfortunately, this approach is often subject to limitations. As a result, increasing attention within the chemical sensor community is turning to the use of analyte-specific molecular indicators, wherein substrate-triggered reactions are used to signal the presence of a given analyte. This <I>tutorial review</I> highlights recent reaction-based indicator systems that have been used to detect selected anions, cations, reactive oxygen species, and neutral substrates.</P> <P>Graphic Abstract</P><P>This tutorial review describes current progress in the development of reaction-based indicators that show promise for use in detecting various anions, cations, reactive oxygen species, and neutral substrates. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b804436h'> </P>

Disulfide-Based Multifunctional Conjugates for Targeted Theranostic Drug Delivery

Lee, Min Hee,Sessler, Jonathan L.,Kim, Jong Seung American Chemical Society 2015 Accounts of chemical research Vol.48 No.11

<title>Conspectus</title><P>Theranostics, chemical entities designed to combine therapeutic effects and imaging capability within one molecular system, have received considerable attention in recent years. Much of this interest reflects the promise inherent in personalized medicine, including disease-targeted treatments for cancer patients. One important approach to realizing this latter promise involves the development of so-called theranostic conjugates, multicomponent constructs that selectively target cancer cells and deliver cytotoxic agents while producing a readily detectable signal that can be monitored both <I>in vitro</I> and <I>in vivo</I>. This requires the synthesis of relatively complex systems comprising imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands. Ideally, the cleavage process should take place within or near cancer cells and be activated by cellular components that are associated with cancer states or specifically expressed at a higher level in cancer cells. Among the cleavable linkers currently being explored for the construction of such localizing conjugates, disulfide bonds are particularly attractive. This is because disulfide bonds are stable in most blood pools but are efficiently cleaved by cellular thiols, including glutathione (GSH) and thioredoxin (Trx), which are generally found at elevated levels in tumors. When disulfide bonds are linked to fluorophores, changes in emission intensity or shifts in the emission maxima are typically seen upon cleavage as the result of perturbations to internal charge transfer (ICT) processes. In well-designed systems, this allows for facile imaging. In this Account, we summarize our recent studies involving disulfide-based fluorescent drug delivery conjugates, including preliminary tests of their biological utility <I>in vitro</I> and <I>in vivo</I>.</P><P>To date, a variety of chemotherapeutic agents, such as doxorubicin, gemcitabine, and camptothecin, have been used to create disulfide-based conjugates, as have a number of fluorophores, including naphthalimide, coumarin, BODIPY, rhodol, and Cy7. The resulting theranostic core (drug–disulfide–fluorophore) can be further linked to any of several site-localizing entities, including galactose, folate, biotin, and the RGD (Arg-Gly-Asp) peptide sequence, to create systems with an intrinsic selectivity for cancer cells over normal cells. Site-specific cleavage by endogenous thiols serves to release the cytotoxic drug and produce an easy-to-monitor change in the fluorescence signature of the cell. On the basis of the results summarized in this Account, we propose that disulfide-based cancer-targeting theranostics may have a role to play in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/achre4/2015/achre4.2015.48.issue-11/acs.accounts.5b00406/production/images/medium/ar-2015-00406b_0018.gif'></P>

A Calix[4]arene Strapped Calix[4]pyrrole: An Ion-Pair Receptor Displaying Three Different Cesium Cation Recognition Modes

Kim, Sung Kuk,Sessler, Jonathan L.,Gross, Dustin E.,Lee, Chang-Hee,Kim, Jong Seung,Lynch, Vincent M.,Delmau, Lætitia H.,Hay, Benjamin P. American Chemical Society 2010 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.132 No.16

<P>An ion-pair receptor, the calix[4]pyrrole-calix[4]arene pseudodimer <B>2</B>, bearing a strong anion-recognition site but not a weak cation-recognition site, has been synthesized and characterized by standard spectroscopic means and <I>via</I> single-crystal X-ray diffraction analysis. In 10% CD<SUB>3</SUB>OD in CDCl<SUB>3</SUB> (v/v), this new receptor binds neither the Cs<SUP>+</SUP> cation nor the F<SUP>−</SUP> anion when exposed to these species in the presence of other counterions; however, it forms a stable 1:1 solvent-separated CsF complex when exposed to these two ions in concert with one another in this same solvent mixture. In contrast to what is seen in the case of a previously reported crown ether “strapped” calixarene−calixpyrrole ion-pair receptor <B>1</B> (J. Am. Chem. Soc. 2008, 130, 13162−<lpage>13166</lpage>), where Cs<SUP>+</SUP> cation recognition takes place within the crown, in <B>2</B>·CsF cation recognition takes place within the receptor cavity itself, as inferred from both single-crystal X-ray diffraction analyses and <SUP>1</SUP>H NMR spectroscopic studies. This binding mode is supported by calculations carried out using the MMFF94 force field model. In 10% CD<SUB>3</SUB>OD in CDCl<SUB>3</SUB> (v/v), receptor <B>2</B> shows selectivity for CsF over the Cs<SUP>+</SUP> salts of Cl<SUP>−</SUP>, Br<SUP>−</SUP>, and NO<SUB>3</SUB><SUP>−</SUP> but will bind these other cesium salts in the absence of fluoride, both in solution and in the solid state. In the case of CsCl, an unprecedented 2:2 complex is observed in the solid state that is characterized by two different ion-pair binding modes. One of these consists of a contact ion pair with the cesium cation and chloride anion both being bound within the central binding pocket and in direct contact with one another. The other mode involves a chloride anion bound to the pyrrole NH protons of a calixpyrrole subunit and a cesium cation sandwiched between two cone shaped calix[4]pyrroles originating from separate receptor units. In contrast to what is seen for CsF and CsCl, single-crystal X-ray structural analyses and <SUP>1</SUP>H NMR spectroscopic studies reveal that receptor <B>2</B> forms a 1:1 complex with CsNO<SUB>3</SUB>, with the ions bound in the form of a contact ion pair. Thus, depending on the counteranion, receptor <B>2</B> is able to stabilize three different ion-pair binding modes with Cs<SUP>+</SUP>, namely solvent-bridged, contact, and host-separated.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2010/jacsat.2010.132.issue-16/ja100715e/production/images/medium/ja-2010-00715e_0014.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja100715e'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja100715e'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja100715e'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja100715e'>ACS Electronic Supporting Info</A></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja100715e'>ACS Electronic Supporting Info</A></P>

Naphthalimide trifluoroacetyl acetonate: a hydrazine-selective chemodosimetric sensor

Lee, M.,Yoon, B.,Kim, J.,Sessler, J. THE ROYAL SOCIETY OF CHEMISTRY 2013 Chemical science Vol.4 No.11

A dicationic calix[4]pyrrole derivative and its use for the selective recognition and displacement-based sensing of pyrophosphate

Sokkalingam, P.,Kim, D.,Hwang, H.,Sessler, J.,Lee, C. H. THE ROYAL SOCIETY OF CHEMISTRY 2012 Chemical Science Vol.3 No.6

Calix[4]pyrrole-calix[4]arene-crown-5 conjugate with flexible linkers as a model for a selective ion-pair container.

Park, In-Won,Kim, Sung-Kuk,Lee, Mee-Ja,Lynch, Vincent M,Sessler, Jonathan L,Lee, Chang-Hee Wiley-VCH 2011 Chemistry - An Asian Journal Vol.6 No.11

Electroreduction and Acid–Base Properties of Dipyrrolylquinoxalines

Fu, Zhen,Zhang, Min,Zhu, Weihua,Karnas, Elizabeth,Mase, Kentaro,Ohkubo, Kei,Sessler, Jonathan L.,Fukuzumi, Shunichi,Kadish, Karl M. American Chemical Society 2012 The journal of physical chemistry. A, Molecules, s Vol.116 No.41

<P>The electroreduction and acid–base properties of dipyrrolylquinoxalines of the form H<SUB>2</SUB>DPQ, H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>), and H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB>2</SUB> were investigated in benzonitrile (PhCN) containing 0.1 M tetra-<I>n</I>-butylammonium perchlorate (TBAP). This study focuses on elucidating the complete electrochemistry, spectroelectrochemistry, and acid–base properties of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> (<I>n</I> = 0, 1, or 2) in PhCN before and after the addition of trifluoroacetic acid (TFA), tetra-<I>n</I>-butylammonium hydroxide (TBAOH), tetra-<I>n</I>-butylammonium fluoride (TBAF), or tetra-<I>n</I>-butylammonium acetate (TBAOAc) to solution. Electrochemical and spectroelectrochemical data provide support for the formation of a monodeprotonated anion after disproportionation of a dipyrrolylquinoxaline radical anion produced initially. The generated monoanion is then further reduced in two reversible one-electron-transfer steps at more negative potentials in the case of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>) and H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB>2</SUB>. Electrochemically monitored titrations of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> with OH<SUP>–</SUP>, F<SUP>–</SUP>, or OAc<SUP>–</SUP> (in the form of TBA<SUP>+</SUP>X<SUP>–</SUP> salts) give rise to the same monodeprotonated H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> produced during electroreduction in PhCN. This latter anion can then be reduced in two additional one-electron-transfer steps in the case of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>) and H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB>2</SUB>. Spectroscopically monitored titrations of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> with X<SUP>–</SUP> show a 1:2 stoichiometry and provide evidence for the production of both [H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB>]<SUP>−</SUP> and XHX<SUP>–</SUP>. The spectroscopically measured equilibrium constants range from log β<SUB>2</SUB> = 5.3 for the reaction of H<SUB>2</SUB>DPQ with TBAOAc to log β<SUB>2</SUB> = 8.8 for the reaction of H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB>2</SUB> with TBAOH. These results are consistent with a combined deprotonation and anion binding process. Equilibrium constants for the addition of one H<SUP>+</SUP> to each quinoxaline nitrogen of H<SUB>2</SUB>DPQ, H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>), and H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB>2</SUB> in PhCN containing 0.1 M TBAP were also determined via electrochemical and spectroscopic means; this gave rise to log β<SUB>2</SUB> values ranging from 0.7 to 4.6, depending upon the number of nitro substituents present on the H<SUB>2</SUB>DPQ core. The redox behavior of the H<SUB>2</SUB>DPQ(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> compounds of the present study were further analyzed through comparisons with simple quinoxalines that lack the two linked pyrrole groups, i.e., Q(NO<SUB>2</SUB>)<SUB><I>n</I></SUB> where <I>n</I> = 0, 1, or 2. It is concluded that the pyrrolic substituents play a critical role in regulating the electrochemical and spectroscopic features of DPQs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpcafh/2012/jpcafh.2012.116.issue-41/jp3074706/production/images/medium/jp-2012-074706_0017.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp3074706'>ACS Electronic Supporting Info</A></P>