Brice Kauffmann

Helix-rod host-guest complexes with shuttling rates much faster than disassembly.

A molecular helix wrapped around a rigid rod can unwind and move between binding sites. Dynamic assembly is a powerful fabrication method of complex, functionally diverse molecular architectures, but its use in synthetic nanomachines has been hampered by the difficulty of avoiding reversible attachments that result in the premature breaking apart of loosely held moving parts. We show that molecular motion can be controlled in dynamically assembled systems through segregation of the disassembly process and internal translation to time scales that differ by four orders of magnitude. Helical molecular tapes were designed to slowly wind around rod-like guests and then to rapidly slide along them. The winding process requires helix unfolding and refolding, as well as a strict match between helix length and anchor points on the rods. This modular design and dynamic assembly open up promising capabilities in molecular machinery.

Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose

The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements. Starting from a first-principles design taking size, shape and hydrogen-bonding ability into account and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallize, a sequence that binds to β-D-fructopyranose in organic solvents with atomic-scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol for the development of selective receptors.

Cascading transformations within a dynamic self-assembled system

Molecular subcomponents such as phosphate groups are often passed between biomolecules during complex signalling cascades, the flow of which define the motion of the machinery of life. Here, we show how an abiological system consisting of organic subcomponents knitted together by metal-ion coordination can respond to simple signals in complex ways. A Cu(I)(3) helicate transformed into its Zn(II)(2)Cu(I) analogue following the addition of zinc(II), and the ejected copper(I) went on to induce the self-assembly of a Cu(I)(2) helicate from other free subcomponents present in solution. The addition of an additional subcomponent, 8-aminoquinoline, resulted in the formation of a third, more stable Cu(I)(3) helicate, requiring the destruction of both the Zn(II)(2)Cu(I) and Cu(I)(2) helicates to scavenge sufficient Cu(I) for the new structure. This system thus demonstrates two examples in which the application of one signal provokes two distinct responses involving the creation or destruction of complex assemblies as the system seeks thermodynamic equilibrium following perturbation.

Quadruple and Double Helices of 8‐Fluoroquinoline Oligoamides

The assembly of molecular strands into multiple helical hybrids represents a major strategy that nature uses to control elongated supramolecular architectures such as nucleic acids, collagen, or other coiled strands. Multiple-helix formation from non-natural oligomers has thus emerged as an important subject. Nucleic acids and some artificial oligomers adopt a single-stranded helical conformation in the monomeric state and can wind around one another without significantly changing their helical pitch. In other hybrids, for example, pyridine carboxamide oligomers and gramicidin D, compact single-helical conformers must increase their helical pitch and undergo a springlike extension to accommodate a complementary strand and wind into a double helix (Scheme 1, top). For those latter hybrids, double-helix formation thus critically depends on the ease of increasing the helical pitch. We recently found that the hybridization of pyridine carboxamide oligomers is dramatically enhanced when one unit that is designed to enlarge the helix diameter—that is, consisting of three fused aromatic rings—is introduced in the sequence, precisely because this unit lowers the enthalpic cost of springlike extension. Aggregation and, possibly, hybridization are also promoted in helical pyridine–pyridazine oligomers because of their large diameter. Intrigued by the possible outcomes of using exclusively units that give rise to a large helix diameter, we designed tetrameric and octameric amides of 7-amino-8-fluoro-2-quinolinecarboxylic acid, compounds 1 and 2. Herein, we present their remarkable

Diastereoselective encapsulation of tartaric acid by a helical aromatic oligoamide.

A helical aromatic oligoamide foldamer encapsulates tartaric acid with exceptional affinity, selectivity, and diastereoselectivity. The structure of the complex has been elucidated both in solution by NMR spectroscopy and in the solid state by X-ray crystallography, making it possible to rationalize the strong effects observed, particularly the role of hydrogen bonds between the hydroxyl and carboxylic acid groups of tartaric acid and the inner wall of the helically folded capsule, which completely surrounds the guest and insulates it from the solvent.

Converting sequences of aromatic amino acid monomers into functional three-dimensional structures: second-generation helical capsules.

The relationships between primary sequence, folded structure, and function are the basic tenets of nucleic acids and protein machineries. Both comprise a main chain that consists of a constant repeat unit—the sugar–phosphate backbone and the a-peptidic backbone—and variable sequences of side chains—nucleobases and amino acid residues—that determine their structure and, ultimately, their function. Foldamers are synthetic oligomers that adopt stable folded conformations. As biopolymers, many foldamers are based on a constant main chain and variable side chains. However, increasing attention is being paid to sequences in which the main chain also features variable components. Some prime examples include hybrid sequences of a and b peptides and hybrid sequences of aliphatic and aromatic units. Here we present our investigation of an oligoamide foldamer sequence containing five different aromatic units. Its folded structure and its function, namely, specific molecular recognition of alkane diols and alkane diamines, are essentially defined by main-chain sequence variations, and the role of side chains is limited to determining solubility. These results represent significant steps towards the elaboration of new, nonnatural codes for sequence–structure– function relationships. Like other aromatic oligoamide foldamers, compound 1 was designed to fold into a robust helical structure stabilized by local conformational preferences at each rotatable bond and by intramolecular aryl–aryl interactions. It is composed of five different units that have all been characterized independently in the context of simpler sequences consisting of only one or two types of units: 8-amino-2-quinolinecarboxylic acid (Q), 2,6-diaminopyridine and 2,6-pyridinedicarboxylic

Template-Induced Screw Motions within an Aromatic Amide Foldamer Double Helix†

Important steps have been made to control motion at the molecular scale in synthetic systems. Examples of elementary molecular motions such as rotations and translations have been reported, as well as combined motions such as coupled rotations, coupled translations, and springlike extensions. In addition, the direction of molecular movements can sometimes be controlled in translations (shuttling) and in rotations. Herein, we focus on a less-investigated motion, the screw motion, which consists of the linear combination of a rotation and a translation. We found that the sliding of two molecular tapes along one another within a double-helical duplex can be controlled by rodlike guests, so that the length of the duplex matches with the length of the guest (Figure 1a). We recently described the ability of some multiturn singlehelical aromatic amide foldamers to wind around rodlike guests and form stable complexes in which the guest resides in the helix cavity. By analogy with rotaxanes, these complexes can be termed foldaxanes. When the rods have bulky residues at the termini, foldaxanes do not form by the threading of the rod into the helix cavity but by the unfolding/ refolding of the helix around the rod. This creates a high kinetic barrier, owing to the high energy cost to unfold a helical aromatic oligoamide foldamer, as shown, for example, in quinolinecarboxamide oligomers. The unusual kinetic stability of the foldaxanes has allowed us to induce and observe shuttling of the helix between distinct stations along a dumbbell rod at timescales that are much shorter than the timescale of foldaxane dissociation. Foldaxane formation is

Self-assembly of supramolecular fullerene ribbons via hydrogen-bonding interactions and their impact on fullerene electronic interactions and charge carrier mobility.

The anisotropy of the electronic interactions between fullerenes in crystalline solids was examined using a confocal fluorescence microscope by probing the polarization of the fluorescence emission arising from fullerene excimer-like emitting states. Crystals of C(60) obtained by vacuum-sublimation or from chloroform solution exhibited no or little polarization (p = 0 or 0.11, respectively), as expected from the high symmetry of the C(60) fcc lattice or the low degree of anisotropy induced by included solvent molecules. The use of hydrogen-bonding to supramolecularly control interfullerene electronic interactions was explored using a fullerene derivative (1) combining a solubilizing 3,4-di-tert-butylbenzene group and a barbituric acid hydrogen-bonding (H-B) moiety. The crystal structure of 1 establishes the existence of fullerene H-B tapes along which interfullerene electronic interactions are expected to be large. In agreement with this, we observe very strong polarization of the fullerene excimer-like emission (p = 0.78), indicative of a high degree of anisotropy in the fullerene interactions. The charge-carrier mobility of 1 as determined from OFET devices was found to be lower than that of C(60) (1.2 x 10(-4) vs 1.2 x 10(-2) cm(2)/s V), which is rationalized on the basis of the reduced dimensionality of 1 as a wire-like semiconductor and variations in the morphology of the device active layer revealed by AFM measurements.

Functional and Structural Aspects of Poplar Cytosolic and Plastidial Type A Methionine Sulfoxide Reductases

The genome of Populus trichocarpa contains five methionine sulfoxide reductase A genes. Here, both cytosolic (cMsrA) and plastidial (pMsrA) poplar MsrAs were analyzed. The two recombinant enzymes are active in the reduction of methionine sulfoxide with either dithiothreitol or poplar thioredoxin as a reductant. In both enzymes, five cysteines, at positions 46, 81, 100, 196, and 202, are conserved. Biochemical and enzymatic analyses of the cysteine-mutated MsrAs support a catalytic mechanism involving three cysteines at positions 46, 196, and 202. Cys46 is the catalytic cysteine, and the two C-terminal cysteines, Cys196 and Cys202, are implicated in the thioredoxin-dependent recycling mechanism. Inspection of the pMsrA x-ray three-dimensional structure, which has been determined in this study, strongly suggests that contrary to bacterial and Bos taurus MsrAs, which also contain three essential Cys, the last C-terminal Cys202, but not Cys196, is the first recycling cysteine that forms a disulfide bond with the catalytic Cys46. Then Cys202 forms a disulfide bond with the second recycling cysteine Cys196 that is preferentially reduced by thioredoxin. In agreement with this assumption, Cys202 is located closer to Cys46 compared with Cys196 and is included in a 202CYG204 signature specific for most plant MsrAs. The tyrosine residue corresponds to the one described to be involved in substrate binding in bacterial and B. taurus MsrAs. In these MsrAs, the tyrosine residue belongs to a similar signature as found in plant MsrAs but with the first C-terminal cysteine instead of the last C-terminal cysteine.

Absolute control of helical handedness in quinoline oligoamides.

The synthesis of quinoline-derived helically folded aromatic oligoamides functionalized by various chiral functions at their N-terminus is reported. When a (1S)-(-)-camphanyl moiety was introduced, it was found that helix handedness was completely shifted to right-handed helicity (de > 99%), in both protic and nonprotic solvents. The absolute helical sense and the de values were unambiguously characterized by using (1)H NMR, circular dichroism (CD), and X-ray crystallography. The crystal structure of these compounds allowed us to propose a rationale for the efficiency of helix handedness induction based on a combination of steric factors and intramolecular hydrogen bonding.