Synthesis, characterization and complexation studies of some novel cyclophane amides and sulfonamides

A series of tricyclic tetraamides have been synthesized and were characterized from spectral and XRD studies. XRD studies revealed that the pyridine-based tricyclic cyclophane amide exists with twisted phenyl rings. All the cyclophane compounds form charge-transfer (CT) complexes with TCNQ. Metal ion complexation studies show that the cyclophane amides are more selective towards Cu(II) ions rather than Ni(II) and Cd(II) ions.     

Synthesis, characterization and ion transportation studies of some novel cyclophane amides

Various novel cyclophane amides with a large cavity have been synthesized. The structures of cyclophane amides 14 and 15 were resolved using XRD studies. Cyclophane amide 28 shows a shift in λ_max in the UV/Vis. spectra when treated with Cu (II) ion as well as with Pb (II) ion. Ion transportation studies were carried out with cyclophane amide 14 which proved that the Na⁺ ion passes through the cavity while K⁺ ions are retained.     

Spectroscopic properties of cyclophane/anthracene and cyclophane/9-fluorenone complexes in dichloromethane

Host/guest interactions of cyclophane/anthracene (C/A) and cyclophane/9-fluorenone (C/F) complexes in dichloromethane, where the cyclophane molecule is the host, are investigated. The stability constants, log K_a, for the C/A and C/F complexes are determined by absorption and fluorescence spectroscopy. For the C/A system, log K_a is 4.2±0.2 as determined from absorption (at 325 nm) and emission (at 382, 403 and 427 nm) spectroscopic data. The analogous measurements yield 3.6±0.2 from absorption (at 309 nm) and emission (at 505 nm) spectroscopic data for the C/F system. Heats of formation of these complexes were determined by measuring the complex association constants at 25, 29 and 32 °C. These results reveal that binding of the anthracene guest by this cyclophane molecule is thermodynamically favored over that for a 9-fluorenone guest. Excited state lifetimes of these systems are also determined.     

Substrate specificity and reaction directionality of a three-residue cyclophane forming enzyme PauB

Three-residue cyclophane-forming enzymes (3-CyFEs) are a group of radical S-adenosylmethionine (SAM) enzymes involved in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs). 3-CyFE catalyzes the crosslinking between an aromatic residue (Ω1) and a non-aromatic residue (X3) in a Ω1-X2-X3 motif to produce a cyclophane ring, a key step in the biosynthesis of the RiPP natural product triceptide. In this study, we perform a genome-wide search for the Xye-type triceptides, showing these RiPPs are likely class-specific and only present in gamma-proteobacteria. The 3-CyFE PauB from Photorhabdus australis exhibits a relaxed substrate specificity on the X3 position, but glycine in this position is not suitable for cyclophane formation. We also reconstituted the activity of PauB in vitro, showing it produces the N-terminal cyclophane firstly, and then the C-terminal ring, whereas the middle cyclophane is produced in the last step.     

Conformational restriction of cyclic dinucleotides with triazole-linked cyclophane analogues

Cyclic dinucleotides (CDN) such as c-di-GMP and c-di-AMP are important multi-functional compounds that regulate a diverse range of processes in bacteria. The diversity of the functions is enabled by the two distinct conformations, that is, open and close conformations. We herein report the concise synthesis of triazole-linked analogues (c-di-GMP^TL, c-di-AMP^TL) through click dimerization of nucleoside analogues. The implementation of a cyclophane system in the central macrocycle furnished the structure with the conformational restriction to maintain the structure similar to the open conformer of natural congeners.     

Complex formation of mono-and binuclear dimeric cyclophane zinc diphenylporphyrinates with pyridine

The formation of host-guest complexes between zinc diphenylporphyrinates of dimeric diphenylporphyrins and pyridine in toluene has been studied by the spectrophotometric titration method and ¹H NMR spectroscopy. The zinc porphyrinates with pyridine form “internal” or “external” 1: 1 or 1: 2 complexes, depending on the length of binding ether O(CH₂)_nO bridges (n = 2, 3) of the cyclophane dimers and the reactant concentration. The stability constants of the porphyrinate-ligand complexes and concentration ranges of their formation have been determined.     

Synthesis and guest-binding study of polytopic multi(cyclophane) hosts

Novel bis(cyclophanes) bearing glucosides and pentakis(cyclophanes) bearing glucosides were prepared as water-soluble hosts by connecting two or five macrocyclic skeletons, respectively. The guest-binding affinities of the present bis(cyclophanes) and pentakis(cyclophanes) toward a hydrophobic dye, 6-p-toluidinonaphthalene-2-sulfonate, were enhanced 13- and 1200-fold, respectively, relative to that by a corresponding monocyclic cyclophane, reflecting multivalency effects in macrocycles.     

Synthesis of a biphenyl-based cyclophane via benzidine rearrangement of a constrained m-nitrophenol derivative

The benzidine rearrangement of a constrained m-nitrophenol derivative results in production of a cyclophane comprising a biphenyl group and a polyether tether connected at the 4,4′ positions.     

Surface plasmon resonance study on binding interactions of multivalent cyclophane hosts with immobilized guests

Guest‐binding affinities of water‐soluble cyclophane heptadecamer (1) and pentamer (2) with immobilized guests such as 1‐pyrenylmethylamine (PMA) and 2‐(1‐ naphthyl)ethylamine (NEA) were investigated by surface plasmon resonance (SPR) measurements. As a typical example, the binding constants (K) for 1 and 2 with the immobilized PMA as a guest were evaluated to be 2.5 × 10⁷ and 2.7 × 10⁶ M^?1, respectively, and were much larger than that of a monocyclic reference cyclophane (K, 2.5 × 10⁴ M^?1). Interestingly, in the complexation of 1 and 2 with the immobilized guests, more favorable association and dissociation rate constant values (k_a and k_d, respectively) were observed in comparison with those for the monocyclic cyclophane, reflecting multivalent effects in macrocycles. The multivalent effects in macrocycles as well as molecular recognition abilities of the cyclophane oligomers were confirmed even when the guest molecules were immobilized on SPR sensor chip surfaces. Copyright © 2009 John Wiley & Sons, Ltd.     

Molecular association of benzene with a new cyclophane receptor

Host/guest interactions in the cyclophane-2/benzene system have been investigated by absorption and fluorescence spectroscopy in dichloromethane. The cyclophane serves as a host and the benzene as a guest. Absorption and fluorescence titration experiments are carried out by holding either the concentration of the host or guest constant while varying the concentration of the other component. When the concentration of benzene is kept constant, an isostilbic point at 288 nm is observed in the fluorescence spectral data, suggesting that only two absorbing species are present in equilibrium. Keeping the concentration of cyclophane-2 constant while increasing the concentration of benzene results in a hyposchromic shift of the emission peaks in the range 275–360 nm. The shift is attributed to interaction of the cyclophane with benzene. The average association constant of cyclophane-2 with benzene, K _a = 425 ± 54 M^?1, obtains from fitting the absorption and the fluorescence spectral data to the Bourson et al. equation using non-linear regression analysis.     

Synthesis of an imidazolium-linked cyclophane from histamine

The synthesis and structural characterization of a dicationic imidazolium-linked cyclophane 7 is reported. In 7, two imidazolium units that have histamine dihydrochloride as a precursor are bridged by two 2,6-bis(bromomethyl)-pyridine.     

Synthesis and structure of N-heterocyclic carbene complexes of rhodium and iridium derived from an imidazolium-linked cyclophane

This paper describes the synthesis, spectroscopic and structural characterisation, and electrochemical behaviour of some rhodium and iridium complexes of the form LM(X₁)(X₂)⁺, where L is a chelating bis(carbene) derived from an imidazolium-linked ortho-cyclophane. The complexes where X₁/X₂ = 1,5-cycooctadiene or norbornadiene were prepared from the imidazolium-linked cyclophane and the appropriate metal source. In these complexes, the M-L bonding was quite robust, but the diene could be displaced by CO to give the dicarbonyl complexes , from which one or both carbonyl ligands could be displaced by monodentate or bidentate phosphines, respectively. Structural studies revealed only minor variations in the cyclophane unit upon exchange of the ancillary ligands, in each case the rhodium complex being isomorphous with its iridium analogue. In cyclovoltammetric studies of LRh(dppe)⁺, reversible Rh(I/II) and Rh(II/III) redox couples were observed. The other rhodium complexes displayed more complex electrochemical behaviours and did not undergo simple reversible redox reactions.     

A general synthesis of bis(n6−[2n]cyclophane)ruthenium(II) compounds

Hydride reduction of (n⁶-arene)(n⁶?[2_n]cyclophane)ruthenium(II) compounds, followed by treatment with acid, gives (n⁶?[2_n]cyclophane)ruthenium(II) solvates and thus provides a general synthesis for bis(n⁶?[2_n]cyclophane)ruthenium(II) compounds.     

Synthesis of a ditopic cyclophane based on the cyclobutane ring by chalcone photocycloaddition

The intramolecular photocycloaddition of chalcones to give cyclobutanes has proven to be a fast and simple method to shrink a cyclophane ring to a tricyclic system, in order to prepare potential ditopic receptors. In particular, the chalcone 1, having dioxyethylene chains as spacers, is converted in high yield to the cyclobutane 2. NOESY spectroscopy indicates that the formation of 2 occurs by a head-to-head syn ring closure.     

Ultra-high pressure synthesis of a tetrathiafulvalene-diquat cyclophane

Quaternization of a tetrathiafulvalene (TTF)/2,2′-bipyridine cyclophane under 10 kbar of pressure yields a TTF-diquat donor-acceptor cyclophane revealing distinct charge-transfer interactions.     

Methylated multibridged [2n]cyclophanes. All alternate synthesis of [26](1,2,3,4,5,6) cyclophane (superphane)

A sequence of formylation followed by a carbene insertion reaction has led to the stepwise introduction of additional ethano bridges into 4,5,7,8- tetramethyl [2₂](1,4)cyclophane ($\text{1}$), providing syntheses of 5,7,8-trimethyl- [2₃](l,2,4)cyclophane ($\text{6}$), a mixture of 5,8-dimethyl[2₄(1,2,4,5)cyclophane ($\text{10}$) and 5,7-dimethyl[2₄(1,2,3,5)cyclophane ($\text{11}$, and-4-methyl[2₅](1,2,3,4,5)-cyclophane ($\text{14}$). This route to $\text{14}$ completes a formal eight-step synthesis of [2₆](1,2,3,4,5,6)cyclophane ($\text{15}$, superphane) with an overall yield of 17%. A Birch reduction of $\text{6}$ readily gave 12,15-dihydro-5,7,8-trimethyl[2₃](1,2,4)-cyclophane ($\text{7}$) in 85% yield.     

Preparation of large macrocyclic tetra-amines consisting of a methylene backbone and a cyclophane type skeleton

Efficient synthetic routes to 1,10,19,28-tetraazacyclohexatriacontane, a 36-membered ring compound with a methylene backbone, and bis(N,N-octamethylene-4,4′-diaminodiphenylmethane), a 38-membered tetra-amine with a cyclophane skeleton, have been developed via reduction of tetralactam and via a double condensation reaction, respectively. Overall yields are 51% with 5 steps for the former, and 46% with 6 steps for the latter, while the corresponding 2 + 2 cyclization gave the cyclic compounds in poor yields, 9% and 4%, respectively, for the 36-membered tetra-aza ring and for the 38-membered cyclophane derivative.     

Preparation and multivalently enhanced guest-binding affinity of water-soluble cyclophane heptadecamers

Water-soluble cyclophane heptadecamers (17a and 17b), which were constructed with the core cyclophane heptadecamer and 36 polar side chains with a terminal galactose or glucose residue, respectively, were prepared. An analogous cyclophane pentamer (5a) was also prepared. The stoichiometry for the complex of the cyclophane oligomers with fluorescence guests such as TNS was confirmed to be 1:1 host:guest by a Job plot. The guest-binding affinity of cyclophane heptadecamers 17a and 17b was much enhanced relative to that of a corresponding monocyclic cyclophane (1a), i.e., the 1:1 binding constant (K) values for 17a with TNS, 2,6-ANS, and 1,8-ANS were ca. 1700-, 1600-, and 1500-fold larger than those of 1a for the identical guests, respectively, which reflects the multivalency effects in macrocycles. Meanwhile, the corresponding K values for the cyclophane pentamer 5a with TNS, 2,6-ANS, and 1,8-ANS were ca. 250-, 250-, and 110-fold larger than those of 1a for the identical guest, respectively.     

Synthesis of a cysteine-linked cyclophane dimer having two rhodamine moieties and its reduction-responsive degradation as studied by fluorescence spectroscopy

Cysteine-linked cyclophane dimer having two rhodamine moieties (2) was synthesized as a reduction-responsive host. Owing to self-quenching property of the two rhodamine moieties, cyclophane dimer 2 showed weak fluorescence intensity relative to that of the rhodamine B moiety itself. The cleavage of disulfide bond of 2 was performed by a treatment with reducing agents such as dithiothreitol, to give the corresponding monomeric cyclophanes having a rhodamine moiety. Such reductive degradation of 2 was detected by the increase on fluorescence intensity. As a host, cyclophane dimer 2 was found to show a stronger guest-binding affinity than the monomeric cyclophanes due to concentration effects of the macrocycles. In addition, reduction-responsive release of entrapped guest molecules by 2 was also monitored by fluorescence spectroscopy.     

Synthesis and solid-state structures of new cyclophane host molecules

Five new cyclophane host molecules (corrals) are prepared by linking together two α,α′-di(4-hydroxyphenyl)-1,4-diisopropylbenzene or α,α′-di(3,5-dimethyl-4-hydroxyphenyl)-1,4-diisopropylbenzene units with two permethylene spacers. Three small cyclophane hosts (boxes) are synthesized by cyclization of α,α′-di(4-hydroxyphenyl)-1,4-diisopropylbenzene with di(bromomethyl)benzene compounds. Solid-state structures of one corral and one box are reported.