3,3'-Bis(acylamino)-2,2'-bipyridine discotics : desymmetrization and functionalization

In the field of supramolecular chemistry control over self-assembly is one of the main targets. This might be accomplished by adaptation of the environment of organic assemblies by allowing their interaction with other molecules or substrates. To do so, the assembling component has to be equipped with a functional site, which requires derivatization. Also, derivatization in itself may result in enhanced, beneficial supramolecular behavior. In this thesis, derivatization of disc-shaped molecules at their periphery is described with the goal of introducing functionality into the discotic systems and of allowing the discotics to perform desirable, programmed interactions with other molecules. The discotics are composed of a central trimesic core and radially equipped with three 2,2'-bipyridinyl-3,3'-diamine moieties that in turn are linked to three gallic moieties decorated with peripheral alkyl tails. In Chapter 1 an overview of functionalized and desymmetrized discotics is given, with the focus on single-core discotics like triphenylenes, hexabenzocoronenes, phthalocyanines, porphyrins and benzene-1,3,5-tricarboxamides. The synthesis of the desymmetrized derivatives as well as their enhanced supramolecular and material properties is described. It is clear that desymmetrization and functionalization of the originally symmetrical discotics allows programmed interaction with other molecules or gives rise to functional materials besides the original focus on one-dimensional assembly and columnar liquid crystals. In Chapter 2, two synthetic strategies to replace one of the 3,4,5-trialkoxyphenyl units of bis(acylamino)-2,2'-bipyridine based discotics with a phenyl (disc 1, Figure 1) or 4-pyridyl (disc 2, Figure 1) unit are proposed. The first synthetic strategy is based on a statistical approach and the second one on a step-wise approach involving protective-group chemistry. Both strategies have afforded the desired non-symmetrical discotics but the second strategy has many advantages over the first one, like easier purification steps and accessibility to multigram amounts of the desired discs and their valuable precursors. Importantly, the desymmetrization does not affect significantly the preorganized hydrogen-bonded structure of the discotics. The self-assembly properties of non-symmetrical discotics 1 and 2 are reported in Chapter 3. Both discotics display helical self-assembly in the mesophase and in apolar solution. Importantly, this assembly of discs 2 is similar to that of their C3-symmetical analogues showing that desymmetrization and functio-nalization of the discotics is feasible without undoing their self-assembly capabilities. In Chapter 4, the interaction of disc 2, possessing a peripheral 4-pyridyl group, with chiral acids is described as well as the supramolecular transfer of chirality. First several acids had to be screened to reveal which acids bind selectively with the discotic without disrupting its supramolecular properties. Apparently, acids of intermediate strength like phosphonic and tartaric acids satisfy this requirement. The appropriate chiral acids have then been used to induce chirality into the helical assemblies of disc 2 in solution. Apparently, the efficiency of the transfer of chirality is not only determined by the strength of the chiral acid, but also by steric effects. The stability of the chiral complex is highly sensitive and depends on the helix stability, the strength of the acid-base complex, and the solubility of the components. Chapter 5 deals with the incorporation of a functionalized discotic in methacrylate based polymers. Desymmetrized discotic 3 (Figure 1) carrying a dangling hydroxy group is synthesized that may act as a starting point for a wide variety of functionalized discotics. This is illustrated by transforming disc 1 into a polymerizable disc carrying a methacrylate group. This disc is then copolymerized under ATRP conditions to afford a disc-functionalized poly(butyl methacrylate) copolymer. The latter may serve as a novel material for supramolecular, fluorescent polymeric nanoparticles. In Chapter 6, a novel C3-symmetrical, heavily fluorinated disc 4 (Figure 1) is introduced. Replacing the originally hydrophobic hydrocarbon periphery by a fluorophilic fluorocarbon periphery (disc 4, Figure 1) allows helical self-assembly in fluorinated media. Teflon star 4 forms very stable columnar mesophases in which helicity may be present. Surprisingly, a proper choice of solvent combination allows the formation of mixed assemblies in which discotics possessing both a chiral, hydrocarbon periphery and fluorinated discotics 4 are present. This allows transfer of chirality from the former to the latter with the expression of amplification of chirality. Figure 1: Discotics described in this thesis. Non-symmetrical discotics 1 and 2 figure as the main topics in Chapters 2, 3 and 4. Hydroxy-disc 3 is applied in Chapter 5 and teflon disc 4 is the key molecule in Chapter 6

Desymmetrization of 3,3'-bis(acylamino)-2,2'-bipyridine based discotics: the high fidelity of the self-assembly behavior in the liquid crystalline state and in solution

Two novel nonsymmetrical disc-shaped molecules 1 and 2 based on 3,3-bis(acylamino)-2,2-bipyridine units were synthesized by means of a statistical approach. Discotic 1 possesses six chiral dihydrocitronellyl tails and one peripheral phenyl group, whereas discotic 2 possesses six linear dodecyloxy tails and one peripheral pyridyl group. Preorganization by strong intramolecular hydrogen bonding and subsequent aromatic interactions induce self-assembly of the discotics. Liquid crystallinity of 1 and 2 was determined with the aid of polarized optical microscopy, differential scanning calorimetry, and X-ray diffraction. Two columnar rectangular mesophases (Colr) have been identified, whereas for C3-symmetrical derivatives only one Colr mesophase has been found.[1] In solution, the molecularly dissolved state in chloroform was studied with 1H NMR spectroscopy, whereas the self-assembled state in apolar solution was examined with optical spectroscopy. Remarkably, these desymmetrized discotics, which lack one aliphatic wedge, behave similar to the symmetric parent compound. To prove that the stacking behavior of discotics 1 and 2 is similar to that of reported C3-symmetrical derivatives, a mixing experiment of chiral 1 with C3-symmetrical 13 has been undertaken; it has shown that they indeed belong to one type of self-assembly. This helical J-type self-assembly was further confirmed with UV/Vis and photoluminescence (PL) spectroscopy. Eventually, disc 2, functionalized with a hydrogen-bonding acceptor moiety, might perform secondary interactions with molecules such as acids

Synthesis of 3,6-Diaminophthalimides for Ureidophthalimide-Based Foldamers

An improved methodol. for the synthesis of a variety of 3,6-diaminophthalimides in high yields was reported. This enables decoration of the periphery of foldamers with a wide range of functionalities. Thus, reaction of 3,4,5-tris[[(3S)-3,7-dimethyloctyl]oxy]benzenamine with N,N'-(1,3-dihydro-1,3-dioxo-4,7-isobenzofurandiyl)bis(acetamide) gave 4,7-diamino-2-[3,4,5-tris[[(3S)-3,7-dimethyloctyl]oxy]phenyl]-1H-isoindole-1,3(2H)-dione via a bis(acetamido)-protected synthetic intermediate

Chiral poly(ureidophthalimide) foldamers in water

Poly(ureidophthalimide)s decorated with hydrophilic side chains, that ensure soly. in aq. media, have been synthesized and characterized by UV/Vis and CD (CD) spectroscopy. Temp. and concn. dependent CD measurements in water have revealed an almost temp. and concentra-ion independent Cotton effect, indicative for a strong intramol. organization. Similar studies in THF demonstrate the dynamic nature of the secondary architecture, a characteristic of foldamers. In addn., the bisignated Cotton effect in water is opposite in sign to that in THF, suggestive for a solvent-dependent preference for one helical handedness. Mixing expts. prove the dominance of water in detg. the handedness of the helical architecture. The solvent allows for control over the helical architecture and thus governs the supramol. synthesis

Radical cation formation in characterization of novel C3-symmetric disks and their precursors by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Four C3-symmetrical tris(dipeptide) disks and their precursors were characterized using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). The C3-symmetrical disks were based on a benzene-1,3,5-triscarboxamide core extended by oligopeptides with trialkoxyanilide tails. The results indicate that MALDI TOF MS is a powerful and straightforward analytical technique for characterizing C3-symmetrical disks and their precursors. Clear (pseudo)-molecular ion peaks could readily be identified. It is remarkable that strong radical ion signals were observed for all the compounds, including the anilines that were expected to be protonated prior to laser irradiation using acidic MALDI matrixes. Possible mechanisms for radical ion formation were investigated with the employment of radical scavengers, with various matrixes and with direct laser desorption/ionization (LDI). Most likely the radicals are formed by losing one electron from the aniline nitrogen and stabilized by conjugation through the phenyl ring. It appears that direct photo/thermal ionization of analytes is an important route for the radical ion formation of the compounds with trialkoxy aniline/anilide groups

Helical self-assembly and amplification in chirality in fluorinated, preorganized discotic systems (mixing on the molecular level with apolar discs)

The synthesis and self-assembly properties of a fluorinated C3-symmetrical 3,3'-bis(acylamino)-2,2'-bipyridine discotic (1) in the mesophase and in solution are described. First, 3,4,5-tris-(1H,1H,2H,2H,3H,3H-perfluoroundecyl-1-oxy)benzoyl chloride was coupled to mono-t-BOC protected 2,2'-bipyridine-3,3'-diamine to afford after deprotection the corresponding fluorinated aromatic amine on a multigram scale. Then, three-fold reaction of this amine with trimesyl chloride yielded the target C3-symmetrical fluorinated disc. The latter displayed columnar liquid crystallinity over a temperature range of more than 350 K in which helical rectangular and hexagonal columnar mesophases were detected by X-ray diffraction measurements. 1H-NMR spectroscopy showed a preorganized structure due to strong intramolecular hydrogen bonding between the amide N–H's and bipyridine nitrogen atoms, even in the presence of a large excess of hexafluoroisopropanol. This preorganized structure allows the formation of helical self-assemblies in fluorinated solvents, as was established using UV-Vis spectroscopy. The fluorinated disc and two chiral hydrocarbon analogues (a C3-symmetrical and a desymmetrized disc) were mixed in a 1:10 v:v mixture of methoxynonafluorobutane (MNFB) and 1,1,2-trichloro-1,2,2-trifluoroethane (Freon 113). Importantly, the C3-symmetrical hydrocarbon disc dissolves only in the presence of fluorinated disc in the latter solvent mixture, proving a mutual interaction. CD spectroscopy performed on these mixtures points to a preference for alternating self-assemblies of fluorinated and chiral hydrocarbon discotics

The degradation and performance of electrospun supramolecular vascular scaffolds examined upon in vitro enzymatic exposure

To maintain functionality during in situ vascular regeneration, the rate of implant degradation should be closely balanced by neo-tissue formation. It is unknown, however, how the implant's functionality is affected by the degradation of the polymers it is composed of. We therefore examined the macro- and microscopic features as well as the mechanical performance of vascular scaffolds upon in vitro enzymatic degradation. Three candidate biomaterials with supramolecularly interacting bis-urea (BU) hard blocks ('slow-degrading' polycarbonate-BU (PC-BU), 'intermediate-degrading' polycarbonate-ester-BU (PC(e)-BU), and 'fast-degrading' polycaprolactone-ester-BU (PCL-BU)) were synthesized and electrospun into microporous scaffolds. These materials possess a sequence-controlled macromolecular structure, so their susceptibility to degradation is tunable by controlling the nature of the polymer backbone. The scaffolds were incubated in lipase and monitored for changes in physical, chemical, and mechanical properties. Remarkably, comparing PC-BU to PC(e)-BU, we observed that small changes in macromolecular structure led to significant differences in degradation kinetics. All three scaffold types degraded via surface erosion, which was accompanied by fiber swelling for PC-BU scaffolds, and some bulk degradation and a collapsing network for PCL-BU scaffolds. For the PC-BU and PC(e)-BU scaffolds this resulted in retention of mechanical properties, whereas for the PCL-BU scaffolds this resulted in stiffening. Our in vitro study demonstrates that vascular scaffolds, electrospun from sequence-controlled supramolecular materials with varying ester contents, not only display different susceptibilities to degradation, but also degrade via different mechanisms. STATEMENT OF SIGNIFICANCE: One of the key elements to successfully engineer vascular tissues in situ, is to balance the rate of implant degradation and neo-tissue formation. Due to their tunable properties, supramolecular polymers can be customized into attractive biomaterials for vascular tissue engineering. Here, we have exploited this tunability and prepared a set of polymers with different susceptibility to degradation. The polymers, which were electrospun into microporous scaffolds, displayed not only different susceptibilities to degradation, but also obeyed different degradation mechanisms. This study illustrates how the class of supramolecular polymers continues to represent a promising group of materials for tissue engineering approaches