Biomedical subjects
Publications and source records attributed to Kazuhiro Yamato.
The hydrogen bond rigidified backbones of aromatic oligoamides are temporarily interrupted by replacing the amide hydrogens with the acid-labile 2,4-dimethoxybenzyl (DMB) group, which allows the efficient preparation of long folding oligomers that, upon removal of the DMB groups, fold into multiturn helices. [structure: see text]
Oligoamide strands that associate in a sequence-specific fashion into hydrogen-bonded duplexes in nonpolar solvents were converted into disulfide cross-linked duplexes in aqueous media. Thus, by incorporating trityl-protected thiol groups, which allows the reversible formation of disulfide bonds, into the oligoamide strands, only duplexes consisting of complementary hydrogen-bonding sequences were formed in aqueous solution as well as in methanol. The sequence-specific cross-linking of oligoamide strands was confirmed by MALDI-TOF, reverse-phase HPLC, and by isolating a cross-linked duplex. This study demonstrates that the sequence-specificity characteristic of multiply hydrogen-bonded systems can be extended into competitive media through the interplay of H-bonding and reversible covalent interactions, based on which a new class of molecular associating and ligating units that are compatible with both polar and nonpolar environments can be conveniently obtained.
Alkoxy side-chain-flanked diarylsulfonamide serves as a reliable structural motif for constructing macrocyclic aromatic tetrasulfonamides. This 90 degrees structural motif is persistent both in solution and in the solid state, which allows the one-step formation of tetrasulfonamide macrocycles. These macrocycles adopt a cone-shaped conformation in solution and in the solid state. For each molecule, an interior cavity surrounded by the aromatic residues is formed. The cavity sizes of the macrocycles can be tuned by incorporating aromatic residues of proper sizes. Guest (solvent) molecules are found in the cavities and bound by side chains. In solution, 1H NMR shows that the cone conformations undergo rapid interconversion at room temperature. The alkoxy side chains are found to be indispensable for maintaining the cone conformation. In addition, these porous molecules self-assemble into hollow tubular structures in the solid state. A variety of host molecules and building blocks for constructing nanoporous solid-state structures can be expected from these molecules.
Aromatic oligoureas are forced into well-defined conformation by incorporated intramolecular hydrogen bonds. Shape-persistent tetraureas macrocycles were obtained in a one-step [2+2] reaction in good yields.
[structures: see text] This article describes the synthetic procedures for the preparation of crescent (and helical) aromatic oligoamides developed in recent years in our laboratory. The large-scale preparation of a variety of monomers derived from various tetrasubstituted benzenes is presented. Three different strategies for constructing various oligomers consisting of meta- and meta/para-linked benzene residues are discussed. Factors affecting coupling efficiency and yields are analyzed. The developed synthetic methods have provided the basis for the preparation of longer oligomers and for the development of solid-phase synthesis.
A class of six-residue, shape-persistent aromatic oligoamide macrocycles bind the guanidinium ion with very high selectivity.
Aromatic tetrasulfonamide macrocycles carrying alkoxy side chains adopt a stable cone conformation in both the solid state and solution.
Factors responsible for the folding of aromatic oligoamides with backbones rigidified by local three-center H-bonds were investigated. The stability of the three-center H-bonds was quantified by the half-lives of amide proton-deuterium exchange reactions, which show that the three-center H-bonds were largely intact at room temperature in the oligomer examined. This result is consistent with our current and previous 2D NMR studies. The overall helical conformation of nonamer 1 was found by variable-temperature NOESY studies to be dynamic. As temperature rose, the end-to-end NOEs rapidly disappeared, while the amide side chain NOEs were still readily detectable, corresponding to the "breath" and stretching of the helix by slightly twisting the local H-bonded rings. Based on the simple repetition of the same structural motif and local conformational preference, undecamer 2 was found to fold into well-defined helical conformation. The predictability of the folding of these backbone-rigidified aromatic oligoamides was demonstrated by a simple modeling method using structural parameters from oligomers with known crystal structures. The reliability and generality of the modeling methods were shown by the excellent agreement between the modeled structures corresponding to 1 and 2 and data from NOESY studies.
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Highly efficient, one-step macrocyclizations leading to the formation of macrocyclic hexa(aramides) in high yields (69-82%) are described. The one-step macrocyclizations were facilitated by the preorganization or folding of the backbones of uncyclized precursors in the course of macrocyclization. The preorganization of backbones was achieved by the presence of localized three-centered hydrogen bonds that were adopted in the design of a class of closely related, backbone-rigidified foldamers. The macrocyclization involved reactions between diacid chloride 1 and diamine 2. The crude reaction mixtures and products were conveniently examined by mass spectrometric method (MALDI-TOF). Compared to most traditional one-step macrocyclizations that usually require high dilution conditions and often lead to very low overall yields of the desired products, cyclic hexamers 3 were obtained as the overwhelmingly major product under a variety of reaction conditions, suggesting the generality of this approach.
Oligo(m-phenylene ethynylenes) (oligo(m-PE)) with backbones rigidified by intramolecular hydrogen bonds were found to fold into well-defined conformations. The localized intramolecular hydrogen bond involves a donor and an acceptor from two adjacent benzene rings, respectively, which enforces globally folded conformations on these oligomers. Oligomers with two to seven residues have been synthesized and characterized. The persistence of the intramolecular hydrogen bonds and the corresponding curved conformations were established by ab initio and molecular mechanics calculations, 1D and 2D (1)H NMR spectroscopy, and UV spectroscopy. Pentamer 5, hexamer 6, and heptamer 7 adopt well-defined helical conformations. Such a backbone-based conformational programming should lead to molecules whose conformations are resilient toward structural variation of the side groups. These m-PE oligomers have provided a new approach for achieving folded unnatural oligomers under conditions that are otherwise unfavorable for previously described, solvent-driven folding of m-PE foldamers. Stably folded structures based on the design principle described here can be developed and may find important applications.
Molecules and assemblies of molecules with well-defined secondary structures have been designed and characterized by controlling noncovalent interactions. By specifying intermolecular interactions, a class of information-storing molecular duplexes have been successfully developed. These H-bonded molecular duplexes demonstrate programmable, sequence-specificity and predictable, tunable stabilities. Based on these highly specific molecular zippers (or glues), a systematic approach to designing self-assembled structures is now feasible. Duplex-directed formation of beta-sheets, block copolymers and templated organic reactions have been realized. By specifying intramolecular noncovalent interactions, a backbone-rigidification strategy has been established, leading to unnatural molecular strands that adopt well-defined, crescent or helical conformations. The generality of this backbone-rigidification strategy has been demonstrated in three different classes of unnatural oligomers: oligoaramides, oligoureas and oligo(phenylene ethynylenes). Large nanosized cavities have been created based on the folding of these helical foldamers. Tuning the size of the nanocavities has been achieved without changing the underlying helical topology. These helical foldamers can serve as novel platforms for the systematic design of nanostructures.
Cyclohexano-15-crown-5, cyclohexano-18-crown-6, dicyclohexano-15-crown-5, and dicyclohexano-18-crown-6, but not dicylohexano-16-crown-5, in THF dissolve potassium metal to form dark blue potassium alkalide solutions at ambient temperature. On standing, the potassium alkalide complexes decompose and the solutions turn colorless at differing rates. Identification of the products provides insight into the decomposition mechanism.