Light-activated ruthenium complexes photobind DNA and are cytotoxic in the photodynamic therapy window.

Downloaded by Korea Advanced Institute of Science & Technology / KAIST on 01 August 2012 Published on 02 May 2012 on http://pubs.rsc.org | doi:10.1039/C2CC32499G View Online / Journal Homepage / Table of Contents for this issue This article is part of the Aromaticity web themed issue Guest editors: Nazario Martín, Michael Haley and Rik Tykwinski All articles in this issue will be gathered together online at www.rsc.org/cc/aroma ChemComm Dynamic Article Links Cite this: Chem. Commun., 2012, 48, 6791–6793 COMMUNICATION Downloaded by Korea Advanced Institute of Science & Technology / KAIST on 01 August 2012 Published on 02 May 2012 on http://pubs.rsc.org | doi:10.1039/C2CC32499G www.rsc.org/chemcomm A rigid donor–acceptor daisy chain dimerwz Dennis Cao,ab Cheng Wang,a Marc A. Giesener,a Zhichang Liua and J. Fraser Stoddart*ab Received 6th April 2012, Accepted 30th April 2012 DOI: 10.1039/c2cc32499g A functionalised cyclobis(paraquat-p-phenylene) attached by a rigid linker to a tetrathiafulvalene unit, which is incapable of self-complexation, forms preferentially a [c2]daisy chain which undergoes rapid disassociation and reassociation on the 1H NMR time-scale above room temperature. Artificial molecular muscles and actuators have become a source of interest in recent years because of their incorporation into nanoelectromechanical systems (NEMS)1 in order to transduce nanoscale molecular motions into macroscopic movements.2 Elastomers,3 conducting polymers,4 and carbon nanotubes,5 capable of actuation, have all been a part of this interest. Simultaneously, mechanically interlocked molecules2 (MIMs) which mimic protein filaments in biological systems, have generated attention since the discrete relative movements of their components can be controlled by a number of different stimuli. To this end, in addition to electrochemicallystimulated doubly bistable [3]rotaxanes,6 both acid–base7 and chemically8b actuated bistable [c2]daisy chains have been introduced. The latter have been designed and synthesised around metal–ligand coordination,8 hydrogen bonding,7,9 hydrophobic,10 and p-donor/acceptor interactions,11 as the sources of their mutual recognition units. More often than not, however, daisy chain monomers self-assemble in solution to give10c–d,11 a mixture of linear and cyclic oligomers, depending on the concentration of the monomer. In the case of donor–acceptor-based daisy chains, there have been numerous attempts to attach flexible donating units to the electron-deficient cyclobis(paraquat-p-phenylene)12 (CBPQT4+) ring. These monomers, however, have shown13 a strong tendency to self-complex, rather than form higher order superstructures, no doubt as a consequence of the considerable entropic penalty associated with the generation of supramolecular polymers, be they cyclic or acyclic. In order to circumvent self-complexation, we envisage that the use of a rigid spacer of an appropriate length between the donor and the CBPQT4+ ring might eliminate the possibility for intramolecular interactions altogether, thus favouring the formation of daisy chains. Herein, we report the synthesis and characterisation of a daisy chain-forming compound 14+ which consists (Fig. 1) of a tetrathiafulvalene (TTF) unit joined by rigid aromatic linkers to a CBPQT4+ ring for the all but exclusive construction of a donor–acceptor [c2]daisy chain. Several important considerations were taken into account in designing 14+, including (i) the rigidity of the linker which was enforced by a phenylacetylene-containing spacer whose length (11.6 Å) is greater than the length (9.9 Å) of the CBPQT4+ cavity, ensuring that self-complexation cannot occur, (ii) the choice of TTF as the electron-rich donor since previously we have noted14 that 1-ethynyl-5-hydroxynaphthalene derivatives have a low binding affinity for the CBPQT4+ ring, and (iii) the use of a phthalimide linker in place of one of the xylylene units in the CBPQT4+ ring because substituents attached to the imide nitrogen are oriented at right angles to the mean plane of the CBPQT4+ ring, a situation which maintains a plane of symmetry in a perpendicular direction, thus avoiding the generation of isomeric [c2]daisy chains. The synthesis (Scheme 1) of 14PF6 begins15 with a Diels– Alder reaction between 2,5-dimethylfuran and maleic anhydride. Subsequent elimination of H2O from the adduct under strongly acidic conditions yields the anhydride 2 which, when condensed with 4-iodoaniline, yields 3. Dibromide 4, generated by the NBS bromination of 3, was hydrolysed to afford the diol 5 in order to ‘‘protect’’ the benzylic bromides during the subsequent Sonogashira coupling. The TTF derivative 616 was then coupled to 5 to yield the intermediate 7. Since standard PBr3 bromination to regenerate the dibromide proved to be too harsh, mesylation of the diol followed by chloride substitution was used to generate the dichloride 8 which was a Center for the Chemistry of Integrated Systems, Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA. E-mail: stoddart@northwestern.edu; Fax: (+1)-847-491-1009; Tel: (+1)-847-491-3793 b NanoCentury KAIST Institute and Graduate School of EEWS (WCU), Korea Advanced Institute of Science and Technology (KAIST), 373-1 Guseong Dong, Yuseong Gu, Daejeon 305-701, Republic of Korea w This article is part of the ChemComm ‘Aromaticity’ web themed issue. z Electronic Supplementary Information (ESI) available: Synthesis and characterization. See DOI: 10.1039/c2cc32499g This journal is c The Royal Society of Chemistry 2012 Fig. 1 The structural formula of 14+ which contains a TTF unit linked to a CBPQT4+ ring by means of a phenylacetylene spacer. Chem. Commun., 2012, 48, 6791–6793 6791 Downloaded by Korea Advanced Institute of Science & Technology / KAIST on 01 August 2012 Published on 02 May 2012 on http://pubs.rsc.org | doi:10.1039/C2CC32499G Scheme 1 Synthesis of 14PF6. reacted in MeCN with an excess of 4,4 0 -bipyridine to yield 92PF6 after counterion exchange. Finally, 1,4-bis(bromomethyl)benzene was reacted with 92PF6 in the presence of template 10 to yield 14PF6 after counterion exchange and purification by high-performance liquid chromatography. High resolution electrospray ionization mass spectrometry of a 3 mM solution of 14PF6 revealed peaks at m/z = 1326.0789 and 2797.1162 Da, corresponding to the loss of one PF6 counterion from the monomer and dimer of 14+, respectively. UV-Vis spectrophotometric investigations on a model TTF compound (S1z) and CBPQT4+ (S24+z) confirm that the TTF units functionalized with a rigid linker bind to the CBPQT4+ ring. Indeed, when handling 14PF6, it was noticeable immediately that the colour of the solution is dependent on the concentration (Fig. 2) and the temperature. At higher concentrations, the green colour resulting from the charge transfer (CT) between TTF and CBPQT4+ persists while, at lower concentrations, the yellow colour corresponding to a characteristic absorption band appears to dominate. A serial dilution of a solution of 14PF6 in MeCN from 2.7 mM down to 0.1 mM reveals (see SIz) a CT band at 780 nm for the interaction between TTF and the CBPQT4+ ring. The intensity of the band decreases as the concentration is lowered. Applying the Benesi–Hildebrand method (see SIz) reveals a nonlinear relationship between the inverse concentration and the inverse change in absorption intensity, an observation which suggests that the formation of the CT complex is most likely the result of dimerisation rather than as a consequence of selfcomplexation or oligomerisation. The equilibrium (Fig. 3a) between the monomer and dimeric [c2]daisy chain can be followed by variable temperature (VT) 1 H NMR spectroscopy. At low temperatures, relatively sharp resonances corresponding to the cyclic dimer can be observed. With the assistance of 1H-1H-g-DQF-COSY and 1H-1H ROESY NMR (see SIz), the resonances for all the protons in 14+ can be assigned (Fig. 3b) at 233 K. The resonances corresponding to the TTF protons are shifted upfield and well Fig. 2 Solutions of 14+ in MeCN demonstrating the change in colour as a function of concentration. 6792 Chem. Commun., 2012, 48, 6791–6793 separated from each other, while the peaks for the methylene protons closest to the phthalimide unit separate into an AX system. We hypothesize that this AX system is a result of the stable nature of the [c2]daisy chain at low temperatures where the imide functionality sits exclusively on one side of the CBPQT4+ face, imposing diastereotopism upon the HMTD protons on opposite sides of the CBPQT4+ ring. As a consequence of the sidedness of the CBPQT4+ ring in the dimeric [c2]daisy chain, the resonances corresponding to the bipyridinium protons, HaD1, HaD2, HbD1, and HbD2, as well as to the phenylene protons, HPBD, also divide up into four and two sets of resonances, respectively. Upon increasing the temperature of a CD3CN solution of 14PF6 from 233 to 323 K, changes occur (Fig. 4) in the 1H NMR spectra. The resonances corresponding to HaD1, HaD2, HbD1, HbD2, and HPBD coalesce between 248 and 263 K, indicating that the rotations of the pyridinium and phenylene rings become fast on the NMR time-scale. The peaks for the protons employed to probe the energy barriers for rotation, using the coalescence method, results17 in very similar energies of activation DGz, namely 13.8–14.5 kcal mol1 from the bipyridinium and phenylene protons, indicating that we are looking at a situation involving numerous probes and realizing they reflect the same mechanism—removal of TTF units from inside CBPQT4+ rings followed by pyridinium and phenylene ring rotations. At around 293 K, whereas the HTTF2D and HTTF3D resonances essentially spread out into the baseline, between 293 and 323 K, some of the peaks begin to shift while the HTTF2D and HTTF3D resonances reappear at around 6.3 ppm, similar to the TTF resonances in the free model compound S1 Fig. 3 (a) The proposed equilibrium between the monomer and dimer of 14+. (b) 1H NMR spectrum (600 MHz, 2 mM, 233 K, CD3CN) of 14PF6 and assignment of the resonances. This journal is c The Royal Society of Chemistry 2012 Downloaded by Korea Advanced Institute of Science & Technology / KAIST on 01 August 2012 Published on 02 May 2012 on http://pubs.rsc.org | doi:10.1039/C2CC32499G Fig. 4 VT 1H NMR spectra (600 MHz, 2 mM, CD3CN) of 14+. (see SIz), indicating that above room temperature there is a fast equilibrium occurring between the monomer and [c2]daisy chain dimer which begins to favour the free species at 323 K. Indeed, when the NMR tube was removed from the spectrometer at 323 K, the solution was yellow, and only returns to green upon cooling to room temperature. Going higher in temperature than 323 K results in the decomposition of the compound. We have demonstrated the preferential formation of a [c2]daisy chain as a consequence of the rigidity in the monomer unit which rules out intramolecular interactions leading to selfcomplexation. The supramolecular complex undergoes rapid disassociation and reassociation on the 1H NMR timescale above RT as indicated by the fact that certain protons on the CBPQT4+ ring undergo fast exchange. The next challenge is to design and synthesize rigid donor–acceptor daisy chains with bistability. This research is supported by the National Science Foundation (NSF) under grant CHE-0924620. D. C. and J. F. S. were supported by the WCU Program (NRF R-31-2008-000-10055-0) funded by the Ministry of Education, Science and Technology, Korea. D. 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The Eyring equation, DGzc = RTln(kch/kBTc) was used to calculate the DGzc value at the lower limit of the Tc value for the (i) HaD1 (Dn = 49.8 Hz, kc = 110.6, Tc = 263 K, DGzc = 14.0  0.1 kcal mol1), (ii) HaD2 (Dn = 14.6 Hz, kc = 32.5, Tc = 248 K, DGzc = 14.5  0.4 kcal mol1), (iii) HbD (Dn = 48.6 Hz, kc = 108.0, Tc = 263 K, DGzc = 14.0  0.1 kcal mol1), and (iv) HPBD (Dn = 47.5 Hz, kc = 105.4, Tc = 258 K, DGzc = 13.8  0.1 kcal mol1) resonances. See: I. O. Sutherland, Annu. Rep. NMR Spectrosc., 1972, 4, 71–235. Chem. Commun., 2012, 48, 6791–6793 6793