Two guest complexation modes in a cyclotriveratrylene-based molecular container

N um ber 39 | 2009 C hem C om m Pages 5769–5924 FEATURE ARTICLE Mikiko Sodeoka and Yoshitaka Hamashima Chiral Pd aqua complex-catalyzed asymmetric C–C bond-forming reactions: a Brønsted acid–base cooperative system ISSN 1359-7345 COMMUNICATION Sheng-Hsien Chiu et al. Two guest complexation modes in a cyclotriveratrylene-based molecular container 1359-7345(2009)39;1-S www.rsc.org/chemcomm Number 39 | 21 October 2009 | Pages 5769–5924 Chemical Communications Discover… Read… Follow… Register today www.rsc.org/chemicalscience Registered Charity Number 207890 N um ber 14 | 2009 C hem C om m Pages 1781–1920 FEATURE ARTICLE Li-Wen Xu, Jie Luo and Yixin Lu Asymmetric catalysis with chiral primary amine-based organocatalysts ISSN 1359-7345 COMMUNICATION Ruizhi Wu, Talal F. Al-Azemi and Kirpal S. Bisht Spatially directional multiarm poly(ε-caprolactone) based on resorcin[4]arene cavitand core 1359-7345(2009)14;1-2 www.rsc.org/chemcomm Number 14 | 14 April 2009 | Pages 1781–1920 Chemical Communications Registered Charity Number 207890 ISSN 1757-9694 www.rsc.org/ibiology Quantitative biosciences from nano to macro 1754-5692(2008)1:1;1-6 Volume 1 | Number 1 | January 2009 | Pages 1–100 1756-5901(2009) 1:1;l-m The Current issue is freely available online - Go online today! Mina Bissell, Editorial Board chair “I am convinced that � nally the time is right to launch a truly unique and multidisciplinary journal that strives to introduce novel technologies to answer signi� cant questions in biology.” www.rsc.org/ibiology Forthcoming Articles 010941 Forthcoming articles include: Microscale electroporation for biological applications Ali Khademhosseini et al, Harvard-MIT, USA Bio-electrospraying embryonic stem cells: interrogating cellular viability and pluripotency Suwan Jayasinghe et al, University College London, UK Cellular observations enabled by microculture: paracrine signaling and population demographics David Beebe et al, University of Wisconsin, USA The compaction of gels by cells: a case of collective mechanical activity Andreas Bausch et al, Technical University of Munich, Germany cc009014_Cover.indd 1 12/03/2009 15:18:01 Volum e 38 | N um ber 5 | 2009 C hem Soc Rev Them ed issue: M etal–organic fram ew orks Pages 1201–1508 TUTORIAL REVIEW Takashi Uemura, Nobuhiro Yanai and Susumu Kitagawa Polymerization reactions in porous coordination polymers ISSN 0306-0012 CRITICAL REVIEW Omar M. Yaghi et al. Secondary building units, nets and bonding in the chemistry of metal–organic frameworks 0306-0012(2009)38:5;1-4 www.rsc.org/chemsocrev Volume 38 | Number 5 | May 2009 | Pages 1201–1508 Chemical Society Reviews www.rsc.org/chemsocrev Registered Charity Number 207890 ‘Chem Soc Rev book of choice’ Why not take advantage of free book chapters from the RSC? Through our ‘Chem Soc Rev book of choice’ scheme Chem Soc Rev will regularly highlight a book from the RSC eBook Collection relevant to your research interests. Read the latest chapter today by visiting the Chem Soc Rev website. The RSC eBook Collection offers:  Over 900 new and existing books  Fully searchable  Unlimited access Why not take a look today? Go online to find out more! www.rsc.org/chemsocrev Volume 36 | Number 9 | September 2007 | Pages 1385 - 1532 Chemical Society Reviews TUTORIAL REVIEW Jason S. Fisk, Robert A. Mosey and Jetze J. Tepe The diverse chemistry of oxazol-5- (4H)-ones ChemSocRev ISSN 0306-0012 0306-0012(2007)36:9;1-8 TUTORIAL REVIEW René Severin and Sven Doye The catalytic hydroamination of alkynes Themed issue: Metal–organic frameworks Guest editors: Jeffrey Long and Omar Yaghi csr038005_Cover.indd 1 07/04/2009 14:22:06 Impact Factor 5.340 Impact Factor 17.419 ISSN 0306-0012 www.rsc.org/chemsocrev Chemical Society Reviews 1359-7345(2009)14;1-2 Pages 1781–1920 N um ber 1 | 2009 C hem ical Science Pages 1–140 ISSN 2041-6520 www.rsc.org/chemicalscience Volume 1 | Number 1 | 2010 Chemical Science Dynamic Editor-in-Chief Professor David MacMillan of Princeton, USA will lead a dynamic international team of Associate Editors who will drive the scientific development and make decisions on the content Unique A dedicated home for findings of exceptional significance from across ALL the chemical sciences. In a break with tradition, the journal will give authors the freedom and flexibility to publish more extensive accounts of their novel research without page restrictions A leader At the forefront of the most exciting developments in the chemical sciences, helping to define the important areas by publishing the most significant cutting-edge research High impact Building on the successes of related RSC flagship journals Chemical Communications and Chemical Society Reviews, both of which enjoy an international reputation for high quality content and speed of publication A new journal for findings of exceptional significance across the chemical sciences Launching mid 2010 Pu bl is he d on 2 9 Ju ne 2 00 9. D ow nl oa de d by U ni ve rs id ad d e O vi ed o on 2 7/ 10 /2 01 4 08 :0 9: 54 . View Article Online / Journal Homepage / Table of Contents for this issue http://dx.doi.org/10.1039/b906075h http://pubs.rsc.org/en/journals/journal/CC http://pubs.rsc.org/en/journals/journal/CC?issueid=CC009039 Two guest complexation modes in a cyclotriveratrylene-based molecular containerw Ming-Jhe Li,a Chien-Chen Lai,b Yi-Hung Liu,a Shie-Ming Penga and Sheng-Hsien Chiu*a Received (in Cambridge, UK) 26th March 2009, Accepted 12th June 2009 First published as an Advance Article on the web 29th June 2009 DOI: 10.1039/b906075h We report the synthesis of a cyclotriveratrylene-based molecular container and its distinctly different modes of complexation with dimethyldiazapyrenium and 4,40-biphenylbisdiazonium ions. Trapping guests in container-like host molecules is a relatively unexplored means of catalyzing reactions, delivering potent molecules, and isolating or protecting reactive chemical species.1 Cyclotriveratrylene (CTV), which was discovered almost a century ago, has a fascinating concave molecular structure that makes it a unique building block for the construction of host molecules.2 Although most simple CTV derivatives display poor guest complexation abilities in solution, linking two of them together in a face-to-face manner with spacers connecting the aromatic rings produces cryptophane-type hosts (Fig. 1) that can bind alkylammonium cations,3 haloalkane units,4 and xenon atoms5 as guests. To allow CTV-based container-like molecules to recognize other possible guest molecules—so that they can also be extended into the field of molecular switches and functional inter- locked molecules—we sought to functionalize the linkers between a pair of CTV units with specific guest-complexing moieties. In particular, we suspected that the significant complexation properties of crown ethers would make oligoethylene glycol chains attractive linkers within CTV-based container-like hosts for a variety of guest species. Herein, we report the synthesis of the CTV-based molecular container 1 and its dual modes of complexation with dimethyl- diazapyrenium (DMDAP) and 4,4 0-biphenylbisdiazonium (BPBD) ions. We synthesized the molecular container 1 in three steps from the dialdehyde 2 (Scheme 1).6 NaBH4-mediated reduction of the dialdehyde 2, followed by oxidation of the resulting diol with pyridinium chlorochromate (PCC), afforded the aldol 3. Condensation of the benzyl alcohol functionalities of three units of 3, catalyzed by Sc(OTf)3, provided the CTV-based trisaldehyde 4.7 Reduction of the three formyl groups of 4 followed by Sc(OTf)3 (8 mol%)-catalyzed macrocyclization/CTV formation gave the desired molecular container 1. Previously, we reported that the molecular cage 5 forms an extremely stable complex with DMDAP through the cooperative effect of many weak [C–H� � �O] hydrogen bonds (Fig. 2).8 Thus, we anticipated that the ethylene glycol chains in the molecular container 1 would similarly assist in stabilizing the positioning of a DMDAP unit within its internal cavity. Because the molecular container 1 has two types of openings (i.e., 24- and 34-membered rings), pairs of which are positioned adjacent and opposite to one another (Fig. 1), we suspected that threading of the termini of the rigid DMDAP guest in solution would mainly occur through either two 24-membered-ring openings or two oppositely located, unequally sized openings.9 Fig. 1 Scheme 1 Synthesis of the CTV-based molecular container 1. aDepartment of Chemistry, National Taiwan University, Taipei, Taiwan, 10617, R.O.C. E-mail: [email protected]; Fax: þ886 2 33661677; Tel: þ886 2 33661675 b Institute of Molecular Biology, National Chung Hsing University and Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan, R.O.C. w Electronic supplementary information (ESI) available: Experimental procedures for the preparation of all new compounds and their characterization data. CCDC 722771 and 722772. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/b906075h 5814 | Chem. Commun., 2009, 5814–5816 This journal is �c The Royal Society of Chemistry 2009 COMMUNICATION www.rsc.org/chemcomm | ChemComm Pu bl is he d on 2 9 Ju ne 2 00 9. D ow nl oa de d by U ni ve rs id ad d e O vi ed o on 2 7/ 10 /2 01 4 08 :0 9: 54 . View Article Online http://dx.doi.org/10.1039/b906075h The 1H NMR spectrum of an equimolar (2 mM) mixture of the molecular container 1 and DMDAP�2PF6 in CDCl3–CD3CN (1 : 1) at ambient temperature displays significant changes in the chemical shifts of the protons of the complex relative to those of its free components (Fig. 3). We observe no signals of the free species in the spectrum, suggesting that either the rates of complexation and decomplexation are fast under these conditions (i.e., time-averaged signals) or that the rates of complexation and decomplexation are slow on the 1H NMR spectroscopic timescale and the complex forms with a high association constant. The 1H NMR spectrum of a nonstoichiometric mixture of the molecular container 1 (2 mM) and DMDAP�2PF6 (4 mM) in CDCl3–CD3CN (1 : 1) reveals two sets of signals, present in a 1 : 1 ratio, where one set corresponds to the signals of the free DMDAP ions (Fig. 3d) and the other to the signals of a 1 : 1 complex. Thus, the binding stoichiometry of the molecular container 1 to DMDAP is 1 : 1 and the rates of exchange for the complexa- tion and decomplexation processes are slow on the 1H NMR spectroscopic timescale under these conditions. The significant upfield shifts of the aromatic protons Hd of DMDAP and Hc of the molecular container 1 are consistent with the formation of an inclusion complex between the two species. The existence of [C–H� � �O] hydrogen bonds between the two species is supported by the observation of a significant downfield shift in the signal of the methyl protons of the complexed DMDAP unit. No signals for the free species appeared in the 1H NMR spectra upon diluting an equimolar mixture of the molecular container 1 and DMDAP�2PF6 from 1 mM to 10 mM (see the Supporting Informationw), suggesting that the binding affinity of the two units is very strong (Ka 410 5 M�1). Only one set of aromatic signals appeared for the DMDAP21 unit in the 1H NMR spectra recorded after cooling an equimolar (2 mM) solution of the molecular container 1 and DMDAP�2PF6 in CDCl3–CD3CN (1 : 1) from 298 to 253 K, suggesting that the chemical environments of the two cationic pyridinium motifs were identical in the complex under these conditions. This behavior, in conjunction with the slow exchange characteristics, led us to suspect that the structure of the complex [1*DMDAP][2PF6] in CDCl3–CD3CN (1 : 1) featured the cationic termini of DMDAP21 positioned within two different DB24C8-like openings (Fig. 2). We grew single crystals suitable for X-ray crystallography through liquid diffusion of isopropyl ether into an equimolar CH3CN solution of the molecular container 1 and DMDAP� 2PF6. 10,11 The solid state structure confirms our proposed binding geometry for the complex [1*DMDAP]21 (Fig. 4): the two N-methylpyridinium units of DMDAP21 are threaded through two DB24C8-like openings and 12 [C–H� � �O] hydrogen bonds are formed between the methyl and a-pyridinium C–H units and the oxygen atoms on the ethylene glycol chains.11 It has been reported that small crown ethers, such as 18C6 and 21C7, can form such stable complexes with diazonium ions that their further reactions are inhibited.12 Although the complexation of larger crown ethers with diazonium ions is relatively weak, we suspected that the collaborative effect of the six triethylene glycol chains in the molecular container 1 would allow its complexation to the 4,40-biphenylbisdiazonium (BPBD) ion with reasonable affinity. Single crystals suitable for X-ray crystallography were grown through diffusion of isopropyl ether into an equimolar CH3CN solution of the molecular container 1 and BPBD�2PF6; the solid state structure revealed13 a binding mode for the 1 : 1 complex in which one of the diazonium moieties of BPBD21 is located within the cavity of the DB24C8-like unit and the other is positioned within the oppositely located 34-membered ring (Fig. 5). Upon titration with BPBD�2PF6, the 1H NMR spectra of a solution of the molecular cage 1 in CDCl3–CD3CN (1 : 1) at Fig. 2 Fig. 3 Partial 1H NMR spectra [400 MHz, CDCl3–CD3CN (1 : 1), 298 K] of (a) the molecular container 1, (b) an equimolar (2 mM) mixture of 1 and DMDAP�2PF6, (c) DMDAP�2PF6, and (d) a mixture of 1 (2 mM) and DMDAP�2PF6 (4 mM). Fig. 4 Ball-and-stick representation of the solid state structure of the complex [1*DMDAP]21. This journal is �c The Royal Society of Chemistry 2009 Chem. Commun., 2009, 5814–5816 | 5815 Pu bl is he d on 2 9 Ju ne 2 00 9. D ow nl oa de d by U ni ve rs id ad d e O vi ed o on 2 7/ 10 /2 01 4 08 :0 9: 54 . View Article Online http://dx.doi.org/10.1039/b906075h room temperature display (see the Supporting Informationw) an increase in the intensities of the signals of the complex together with a decrease in those of the free molecular container 1. The spectra suggest that the binding stoichiometry of the molecular container 1 to BPBD�2PF6 is 1 : 1 and that the rates of exchange during the complexation and decomplexation processes are slow under these conditions. Unlike the complexation between the molecular container 1 and DMDAP�2PF6, which displayed only one set of signals for the complexed DMDAP21 units, the complexation between molecular container 1 and BPBD�2PF6 gave two sets of signals for the protons of the complexed BPBD21 moieties. Theoretically, threading this bisdiazonium ion through oppositely located 24- and 34-membered-ring openings would result in a 1H NMR spectrum displaying two sets of signals with equal intensity for the desymmetrized a and b protons of the complexed BPBD21 unit. We find, however, that the integration ratios of the signals in the various spectra were not close to 1 : 1, suggesting that two or more complexation modes are possible in solution; e.g., the two diazonium units of BPBD21 are located within two DB24C8-like openings, as we observed for the complexation of the molecular container 1 and DMDAP21, or within oppositely located 24- and 34-membered rings. When we cooled an equimolar (2 mM) mixture of the molecular container 1 and BPBD�2PF6 in CDCl3–CD3CN (1 : 1) to 253 K, signals representative of the desymmetrized complexed structure disappeared while the other remained as a sharp AB pattern. This result suggested that the two diazonium moieties of BPBD�2PF6 were positioned within the cavities of identically sized macrocyclic rings of the molecular container 1. Because the smaller DB24C8-like units in the molecular container 1 presumably interact with the diazonium ions more strongly than do the larger 34-membered-ring units, we suspect that threading of both diazonium moieties through two DB24C8-like cavities is most likely the predominant structure at low temperature. The linking of two CTV units with six triethylene glycol chains provides a molecular container 1 that is capable of complexing DMDAP21 and BPBD21 ions in solution. We have identified two possible binding modes for molecular container 1 to complex with these linear cationic species. This unique molecular container has the potential to be applied to the construction of novel interlocked molecules and molecular machines. Currently, we are synthesizing molecular containers of different sizes and are investigating the possibility of incarcerating guest units within them. This study was supported by the National Science Council, Taiwan (NSC-95-2113-M-002-016-MY3). Notes and references 1 (a) D. J. Cram and J. M. Cram, Container Molecules and Their Guests, Royal Society of Chemistry, Cambridge, 1994; (b) A. Jasat and J. C. Sherman, Chem. Rev., 1999, 99, 931; (c) L. R. Macgillivray and J. L. Atwood, Angew. Chem., Int. Ed., 1999, 38, 1019; (d) M. Yoshizawa andM. Fujita, Pure Appl. Chem., 2005, 77, 1107; (e) G. Seeber, B. E. F. Tiedemann and K. N. Raymond, Top. Curr. Chem., 2006, 265, 147; (f) S. Biros and J. Rebek, Jr, Chem. Rev., 2007, 36, 93; (g) O. Ugono, J. P. Moran and K. T. Holman, Chem. Commun., 2008, 1404; (h) S. Liu and B. C. Gibb, Chem. Commun., 2008, 3709. 2 (a) A. Collet, Tetrahedron, 1987, 43, 5725; (b) J. W. Steed and J. L. Atwood, Supramolecular Chemistry, Wiley, Chichester, 2000; (c) J. M. Knaust, C. Inman and S. W. Keller, Chem. Commun., 2004, 492; (d) K. T. Holman, in Encyclopedia of Supramolecular Chemistry, ed. J. Atwood, Marcel Dekker, New York, 2004, p. 340; (e) T. Brotin and J.-P. Datasta, Chem. Rev., 2009, 109, 88. 3 (a) L. Garel, B. Lozach, J.-P. Dutasta and A. Collet, J. Am. Chem. Soc., 1993, 115, 11652; (b) M. Miura, S. Yuzawa, M. Takeda, M. Takeda, Y. Habata, T. Tanase and S. Akabori, Supramol. Chem., 1996, 8, 53; (c) P. D. Kirchhoff, J. P. Dutasta, A. Collet and J. A. Mccammon, J. Am. Chem. Soc., 1997, 119, 8015. 4 (a) J. Canceill, L. Lacombe and A. Collet, J. Am. Chem. Soc., 1986, 108, 4230; (b) L. Garel, J.-P. Dutasta and A. Collet, Angew. Chem., Int. Ed. Engl., 1993, 32, 1169; (c) M. R. Caira, A. Jacobs and L. R. Nassimbeni, Supramol. Chem., 2004, 16, 337. 5 (a) T. Brotin, A. Lesage, L. Emsley and A. Collet, J. Am. Chem. Soc., 2000, 122, 1171; (b) C. Hilty, T. J. Lowery, D. E. Wemmer and A. Pines, Angew. Chem., Int. Ed., 2006, 45, 70; (c) H. A. Fogarty, P. Berthault, T. Brotin, G. Huber, H. Desvaux and J.-P. Dutasta, J. Am. Chem. Soc., 2007, 119, 10332. 6 A. M. Elizarov, T. Chang, S.-H. Chiu and J. F. Stoddart, Org. Lett., 2002, 4, 3565. 7 T. Brotin, V. Roy and J.-P. Dutasta, J. Org. Chem., 2005, 70, 6187. 8 C.-F. Lin, Y.-H. Liu, C.-C. Lai, S.-M. Peng and S.-H. Chiu, Chem.–Eur. J., 2006, 12, 4594. 9 For examples of the binding bipyridinium guests with crown ether- based cryptand hosts, see: (a) F. Huang, H. W. Gibson, W. S. Bryant, D. S. Nagvekar and F. R. Fronczek, J. Am. Chem. Soc., 2003, 125, 9367; (b) A. M.-P. Pederson, R. C. Vetor, M. A. Rouser, F. Huang, C. Slebodnick, D. V. Schoonover and H. W. Gibson, J. Org. Chem., 2008, 73, 5570. 10 Crystallographic data (excluding structure factors) for [1*DMDAP]�2PF6 and [1*BPBD]�2PF6 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publications CCDC 722771 and 722772. 11 Crystal data for [1*DMDAP]�2PF6: [C94H110O24N2� 4CH3CN][2PF6]; Mr ¼ 2106.00; orthorhombic; space group Fdd2; a ¼ 22.4430(6), b ¼ 110.268(3), c ¼ 15.7305(4) Å; V ¼ 42 398.0(19) Å3; rcalcd ¼ 1.320 g cm�3; m(MoKa) ¼ 1.182 mm�1; T ¼ 200(2) K; colorless cubes; 16751 independent measured reflec- tions; Rint ¼ 0.1129; F2 refinement; R1 ¼ 0.1105; wR2 ¼ 0.2540. 12 (a) G. W. Gokel and D. J. Cram, J. Chem. Soc., Chem. Commun., 1973, 481; (b) R. A. Bartsch, H. Chen, N. F. Haddock and P. N. Juri, J. Am. Chem. Soc., 1976, 98, 6753; (c) R. M. Izatt, J. D. Lamb, C. S. Swain, J. J. Christensen and B. L. Haymore, J. Am. Chem. Soc., 1980, 102, 3032. 13 Crystal data for [1*BPBD]�2PF6: [C90H104O24N4� 5CH3CN][2PF6]; Mr ¼ 2120.98; triclinic; space group P�1; a ¼ 15.2574(6), b ¼ 15.6396(6), c ¼ 24.9315(9) Å; V ¼ 5192.4(3) Å3; rcalcd ¼ 1.357 g cm�3; m(MoKa) ¼ 1.219 mm�1; T ¼ 250(2) K; red cubes; 18 667 independent measured reflections; Rint ¼ 0.0189; F2 refinement; R1 ¼ 0.0734; wR2 ¼ 0.2072. Fig. 5 Ball-and-stick representation of the solid state structure of the complex [1*BPBD]21. 5816 | Chem. Commun., 2009, 5814–5816 This journal is �c The Royal Society of Chemistry 2009 Pu bl is he d on 2 9 Ju ne 2 00 9. D ow nl oa de d by U ni ve rs id ad d e O vi ed o on 2 7/ 10 /2 01 4 08 :0 9: 54 . View Article Online http://dx.doi.org/10.1039/b906075h