An Autocatalytic System of Photooxidation-Driven Substitution Reactions on a Fe^II₄L₆Cage Framework

The functions of life are accomplished by systems exhibiting nonlinear kinetics: autocatalysis, in particular, is integral to the signal amplification that allows for biological information processing. Novel synthetic autocatalytic systems provide a foundation for the design of artificial chemical networks capable of carrying out complex functions. Here we report a few Feᴵᴵ₄L₆ cages containing BODIPY chromophores having tuneable photosensitizing properties. Electron-rich anilines were observed to displace electrondeficient anilines at the dynamic-covalent imine bonds of these cages. When iodoaniline residues were incorporated, heavy-atom effects led to enhanced ¹O₂ production. The incorporation of (methylthio)aniline residues into a cage allowed for the design of an autocatalytic system: oxidation of the methylthio groups into sulfoxides make them electron-deficient and allows their displacement by iodoanilines, generating a better photocatalyst and accelerating the reaction.This work was funded by the European Research Council (259352).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/ange.20150704

Stimuli-Responsive Metal-Ligand Assemblies.

The Engineering and Physical Sciences Research Council and the European Research Council are acknowledged for financial support.This is the accepted manuscript of a paper published in Chemical Reviews (McConnell AJ, Wood CS, Neelakandan PP, Nitschke JR, Chemical Reviews (2015) 115(15):7729-7793. doi:10.1021/cr500632f). The final version is available at http://dx.doi.org/10.1021/cr500632

DNA-assisted long-lived excimer formation in a cyclophane

A color-changed sandwich: A novel water-soluble cyclophane containing anthracene and imidazolium moieties (see structure) exhibits dual emission in aqueous medium and undergoes sequence-selective interactions with DNA but not with proteins and micelles. In the presence of DNA, it forms a sandwich-type excimer, which exhibits an unusually long lifetime (T) and red-shifted emission. This cyclophane can be used for DNA recognition through "turned on" excimer emission

Encapsulation of electron donor-acceptor dyads in β-cyclodextrin cavity: unusual planarization and enhancement in rate of electron-transfer reaction

Interaction of β-cyclodextrin (β-CD) with a few novel electron donor acceptor dyads 1a-c and 2a-c, having aryl and flexible methylene spacer groups, has been investigated through photophysical, chiroptical, electrochemical, NMR, and microscopic techniques. Dyads 1a and 1c, with p-tolyl and biphenyl spacer groups, respectively, exhibited significantly decreased fluorescence quantum yields and lifetimes in the presence of β-CD, while negligible changes were observed for dyad 1b with an o-tolyl spacer. In contrast, spacer-length-dependent significant enhancement in fluorescence quantum yields and lifetimes was observed for dyads 2a-c, with flexible polymethylene (n = 1, 3, 11) spacer groups. Association constants of β-CD encapsulated complexes have been determined and the contrast behavior observed in these systems is explained through an electron transfer (k<SUB>ET</SUB>) mechanism based on calculated favorable change in free energy (ΔG<SUB>ET</SUB> = −1.27 eV) and the redox species characterized through laser flash photolysis studies. Rates of k<SUB>ET</SUB> have been estimated and are found to increase ca. 2-fold in the case of dyads 1a and 1c when encapsulated in β-CD, while significantly decreased k<SUB>ET</SUB> values were observed for the dyads 2a-c with flexible spacer (ca. 9-fold for 2c). As characterized through cyclic voltammetry, 2D NMR [correlated (COSY) and nuclear Overhauser enhancement (NOESY) spectroscopy], and laser flash photolysis studies, theβ-CD encapsulation of dyads with aliphatic spacer groups leads to the conformational unfolding of a sandwich type of structure, whereas dyads with rigid aryl spacer groups undergo unusual planarization as compared to the uncomplexed dyads, resulting in enhanced electron-transfer reaction between the donor and acceptor moieties

A supramolecular ON-OFF-ON fluorescence assay for selective recognition of GTP

With the objective of developing small molecule based receptors for nucleosides and nucleotides, interactions of a cyclic donor-acceptor conjugate 1 with adenosine, AMP, ADP, CTP, UTP, ITP, ATP, and GTP have been investigated by absorption, steady-state, and time-resolved fluorescence, cyclic voltammetry (CV), NMR, and fluorescence indicator displacement techniques. Titration of 1 with the fluorescent indicator, 8-hydroxy-1,3,6-pyrene trisulfonate (HPTS), resulted in nearly complete fluorescence quenching of HPTS, along with 25% hypochromicity in its absorption spectrum. Benesi-Hildebrand analysis gave a 1:1 stoichiometry for the complex between the receptor 1 and HPTS with an association constant (Kass) of 4.66 × 104 M−1 in buffer. The driving force for such a complexation was evaluated to be the synergistic effects of π-stacking and electrostatic interactions inside the cavity as confirmed by the effect of ionic strength, temperature, and the negative results obtained with the model compound 2. Titration of the nonfluorescent complex [1.HPTS] with various nucleosides and nucleotides resulted in revival of fluorescence of the indicator, HPTS. It was observed that GTP induces maximum displacement of HPTS from the complex [1.HPTS] with an overall fluorescence enhancement of ca. 150-fold. The addition of adenosine, AMP, ADP, CTP, and UTP showed negligible changes, whereas ca. 45- and 50-fold enhancement was observed with ATP and ITP, respectively. The competitive displacement of the indicator by various analytes is found to be in the order GTP (buffer) ≈ GTP (biofluid) » ITP ≈ ATP &gt; UTP &gt; CTP ≈ ADP ≈ AMP ≈ Ade. By virtue of having a better π-electron cloud, GTP undergoes effective electronic, π-stacking, and electrostatic interactions inside the cavity and forms a stable complex with the receptor 1. The uniqueness of this assay is that it differentiates GTP from ATP and other nucleotides and signals the event through a visual "turn on" fluorescence mechanism in buffer as well as in biological fluids

Synthesis of a novel cyclic donor-acceptor conjugate for selective recognition of ATP

Novel cyclophane 1 was synthesized, and its interactions with phosphate, adenosine, AMP, ADP, and ATP have been investigated. With addition of ATP, significant decrease in absorbance of 1 was observed, whereas other guest molecules showed negligible effect. The complex between 1 and ATP was confirmed through cyclic voltammetry and 1H NMR. The uniqueness of the system is that it complexes selectively with ATP in a cavity and involves synergistic effects of both electrostatic and π-π stacking interactions

A supramolecular Cu(II) metallocyclophane probe for guanosine 5'-monophosphate

We demonstrate Cu<SUP>2+</SUP> ion induced formation of a novel water soluble metallocyclophane [1.CuCl<SUB>2</SUB>]<SUB>2</SUB>, which uniquely recognizes guanosine 5'-monophosphate through changes in emission intensity utilizing synergistic effects of electrostatic, coordinative and p-stacking interactions inside the cavity

DNA-assisted white light emission through FRET

We observed FRET between an excimer of a partially intercalated cyclophane and ethidium bromide, a classical intercalator in presence of DNA and by fine-tuning the molar concentrations of these three components, we could generate white light emission in the aqueous and non-aqueous media

Effect of bridging units on photophysical and DNA binding properties of a few cyclophanes

A few novel anthracene-based cyclophanes CP-1, CP-2 and CP-3 were synthesized and their interactions with DNA were investigated employing photophysical and biophysical techniques. In methanol and acetonitrile, these systems exhibited optical properties characteristic of the anthracene chromophore. However, in the aqueous medium, the symmetric cyclophane CP-1 showed a dual emission having λ<SUB>max</SUB> at 430 and 550 nm, due to the monomer and excimer, respectively. In contrast, the cyclophanes CP-2 and CP-3 in the aqueous medium showed structured anthracene absorption and emission spectra similar to those obtained in methanol and acetonitrile. DNA binding studies indicate that CP-1 undergoes efficient nonclassical partial intercalative interactions with DNA resulting in the exclusive formation of a sandwich-type excimer having enhanced emission intensity and lifetimes. The cyclophane CP-2 having one anthracene moiety exhibited nonclassical intercalative binding with DNA, albeit with less efficiency compared with CP-1. In contrast, CP-3, having sterically bulky viologen bridging group showed DNA electrostatic as well as groove binding interactions. These results demonstrate that the nature of the bridging unit plays an important role in the binding mode of the cyclophanes with DNA and in the formation of the novel sandwich-type excimer

Study of cavity size and nature of bridging units on recognition of nucleotides by cyclophanes

We synthesized a few novel cyclophanes CP-1 to CP-4 containing anthracene units linked together through different bridging and spacer groups and have investigated their interactions with various nucleosides and nucleotides. Of these systems, CP-1 and CP-3 showed selectivity for 5'-GTP and 5'-ATP as compared to other nucleotides and nucleosides, whereas negligible selectivity was observed with CP-2 and CP-4. Interestingly, CP-1, CP-2 and CP-3 exhibited significant binding interactions with the fluorescent indicator, 8-hydroxy-1,3,6-pyrene trisulfonate (HPTS), resulting in the formation of non-fluorescent complexes. Titration of these complexes with nucleosides and nucleotides resulted in the displacement of HPTS, leading to the revival of its fluorescence intensity. It was observed that 5'-GTP induced the maximum displacement of HPTS from the complex [CP-1.HPTS] with an overall fluorescence enhancement of ca. 150-fold, while 5'-ATP induced ca. 45-fold. Although the displacement of HPTS from the complexes [CP-2.HPTS] and [CP-3.HPTS] was found to be similar to that of [CP-1.HPTS], these complexes showed lesser selectivity and sensitivity. In contrast, negligible displacement of HPTS was observed from the complex [CP-4.HPTS] under similar conditions. These results indicate that CP-1, having a well-defined cavity and good electron acceptor (viologen), is capable of forming selective and stable complexes. Though CP-2 and CP-3 retain the good electron acceptor (viologen), their reduced aromatic surface and larger cavity, respectively, resulted in lesser sensitivity. In contrast, CP-4 having a large cavity and a poor acceptor (1,2-bis(pyridin-4-yl)ethene) showed negligible selectivity, thereby indicating the importance of cavity size, bridging unit and aromatic surface on biomolecular recognition properties of cyclophanes