Photoinduced conformational changes of azoaromatic polyaspartates containing octadecyl side chains

Copolymers of p-(phenylazo)benzyl-L-aspartate and n-octadecyl-L-aspartate exist as right- and left-handed α-helices in solution at 25°C depending on the copolymer composition: the reversal of helix sense from a right- to left-handed one occurs with increasing the azobenzene content. The α-helices of the copolymers are very sensitive to trifluoroacetic acid (TFA), and are converted into random coil below 2.0% of TFA. Among the copolymers, the copolymer containing 47% azobenzene groups is unique since it exhibits a TFA-induced conformational change from right-handed α-helix to random coil via left-handed α-helix. Upon UV light irradiation at 25°C, the copolymers containing 68 and 89% azobenzene groups caused the reversal in helix sense from a left- to right-handed one. The conformations of the copolymers were dependent on temperature, mostly right-handed and left-handed α-helices at lower and higher temperatures, respectively. On this basis, the copolymer containing 47% azobenzene groups could be made to undergo a photoinduced helix reversal at high temperatures.     

Spontaneously resolved homochiral 3D lanthanide-silver heterometallic coordination framework with extended helical Ln-O-Ag subunits

Two novel homochiral lanthanide-silver heterometallic coordination polymers LnAg(OAc)(IN)3 [Ln = Nd (1), Eu (2), HIN = isonicotinic acid, HOAc = acetic acid] have been prepared under hydrothermal conditions, which were characterized by elemental analysis, infrared, thermogravimetric analysis, and single-crystal X-ray diffraction. Both complexes are isostructural and crystallize in a hexagonal system, chiral space group P6(1)22. Both polymers are constructed from infinite right-handed homochiral helical chains with Ln-O-Ag connectivity, representing the first examples of homochiral lanthanide-transition metal heterometallic coordination polymers with a 3D coordination framework based on spontaneous resolution. Furthermore, the luminescent properties of 2 were studied.     

Homochirality and life

Before the emergence of life, left-handed amino acids (L-enantiomers) were selected and right-handed amino acids (D-enantiomers) were eliminated on the primal earth. Nevertheless, with the progress of analytical methods, D-amino acids have recently been found in higher order living organisms in the form of free amino acids, peptides, and proteins. Free D-amino acids have numerous physiological functions. D-amino acids containing animal peptides are well known as opioid peptides. D-amino acids in protein are related to aging. In this review, we describe the D-amino acids that are present and function as D-amino acid biosystems in our bodies.     

Peptide models. XIV. Ab initio study on the role of side-chain backbone interaction stabilizing the building unit of right- and left-handed helices in peptides and proteins

Previous ab initio computations revealed that the conformational building unit of the right-handed helix (ϕ ≈ −54°, ψ ≈ −45°) is not an energy minimum on two-dimensional-type Ramachandran potential energy surfaces (E = E{ϕ, ψ}). Theoretical investigations were performed on several single-amino-acid diamides such as For-Gly-NH₂, For-L-Ala-NH₂, Ac-L-Ala-NHMe, and For-L-Val-NH₂ containing amino acid residues (e.g., Ala) which can often be found in helices as shown by X-ray data analysis of globular proteins. The current ab initio [self-consistent field (SCF)] results (based on four different basis sets [3-21G, 4-21G, 4-21G^*, and 6-31G^*]) presented point toward an intrinsic (i.e., non-environmental-assisted) stability of the right-handed helical subconformation of a simple amino acid diamide if the residue contains a polar side chain. Such is the case for a serine derivative when its (SINGLE BOND)CH₂OH side chain is favorably oriented. For the For-L-Ser-NH₂ model compound two slightly different right-handed helical backbone conformations were determined. Depending on the relative orientation of the side chain, the conformational monomer of the 3₁₀ helix (a sharper helical structure with an [i, i + 3]-type H-bond network) as well as the building block of the “standard” α-helix (the regular helical structure with an [i, i + 4]-type H-bond network) were determined computationally by geometry optimization. © 1997 John Wiley & Sons, Inc.     

一个手性吡啶甲酸铕(Ⅲ)配合物的合成、晶体结构和荧光性能

合成了1个以2-吡啶甲酸为配体的铕(Ⅲ)配合物[Eu(pic)₃]_n(1),通过红外光谱,元素分析,热重分析和X-射线单晶衍射对其进行了表征。配体2-吡啶甲酸通过其N,O螯合作用桥联了铕(Ⅲ)离子,形成了具有2₁右手螺旋结构的一维链状配合物1。荧光分析表明,配合物1的荧光光谱表现出铕(Ⅲ)的特征光致发光。     

Side-chain chiral centers of amino acid and helical-screw handedness of its peptides

Both diastereomeric right-handed (P) and left-handed (M) 310-helices exist in homopeptides having twelve chiral centers at the side-chain bicyclic skeletons.     

Three 2D Ag(I)-framework isomers with helical structures controlled by the chirality of camphor-10-sulfonic acid

Three 2D Ag(I)-framework isomers were constructed from enantiopure camphor-10-sulfonic acids or racemic camphor-10-sulfonic acids, together with achiral 4-aminobenzoic acids. In complex 1, (+)-camphor-10-sulfonic acids bridge the single left-handed helices that are made up of Ag ions and 4-aminobenzoic acids, generating a homochiral 2D layer. In such a structure, the interweaving of triple left-handed homohelices was also found. It is worth noting that the helicity of complex 2 could be controlled by the handedness of the camphor-10-sulfonic acid. In complex 2, there are right-handed helical structures, including single right-handed and triple right-handed helical structures connected by (-)-camphor-10-sulfonic acids. For a comparative study, (±)-camphor-10-sulfonic acids were utilized to synthesize complex 3, in which equal numbers of right-handed or left-handed double-helical chains are created. All the complexes were characterized by single-crystal X-ray structure determination, powder X-ray diffraction, IR, TGA and element analysis. Circular dichroism spectra of complexes 1 and 2 were been studied to confirm the fact that enantiopure bridging ligands do not racemize.     

Control of peptide helix sense by temperature tuning of noncovalent chiral domino effect

We have investigated temperature effect on control of a peptide helix sense through the noncovalent chiral domino effect (NCDE: Inai, Y. et al., J. Am. Chem. Soc. 2003, 125, 8151-8162). Nonapeptide (1: Inai, Y.; Komori, H. Biomacromolecules 2004, 5, 1231-1240), which alone prefers a right-handed helix, maintained a screw-sense balance or a small imbalance at room temperature in the presence of Boc-d-amino acid. Cooling of the solution induced a left-handed helix more clearly. Conversely, heating from room temperature recovered the original right-handed sense. This helix-helix transition was essentially reversible in cooling-heating cycles. An increase in the Boc-d-amino acid concentration elevated temperature for switching CD signs based on the conformational transition. A similar thermal-driven inversion of helix sense was observed for 1 at other initial concentrations, suggesting that this behavior is insensitive to some peptide aggregation. NMR study provided direct evidence for the domino-type control of helix sense, in which Boc-Leu-OH is mainly located at the N-terminal segment. In addition, a left-handed helix induced by the d-isomer was shown to participate in equilibrium with a right-handed helix, whereas the right-handed helix was predominant in the presence of l-isomer. Consequently, we here have proposed a model for controlling a peptide helix sense (or its screw-sense bias) through temperature tuning of the external chiral interaction specific to the N-terminal sequence.     

Design of an Amphiphilic Perylene Diimide for Optical Recognition of Anticancer Drug through a Chirality-Induced Helical Structure

Introduction of chirality into a supramolecular self-assembly system plays an indispensable role in attaining specific molecular recognition ability. Herein, a chiral anticancer drug 5′-deoxy-5-fluorouridine (5′DFU) was explored for inducing the self-assembly of a cationic perylene diimide derivative containing boronic acid groups (PDI-PBA) into a highly ordered right-handed helical structure. As a result, PDI-PBA exhibited a molecular recognition ability towards 5′DFU among other cis-diols and anticancer drugs. With the help of a dynamic covalent bond and favorable hydrogen-bonding interactions, chirality transfer from chiral 5′DFU to achiral PDI-PBA breaks down the strong π–π stacking of PDI-PBA and makes it reorganize into highly ordered helical supramolecular structures. This work provides an insight into chiral anticancer drug tuning interactions of π-chromophores and the inducement of hierarchical self-assembly to achieve specific molecular recognition.     

Right-handed helical structure of expanded oligo(L-leucine) containing [Ru(terpyridine)2]2+ moieties

Expanded oligo(l-leucine)s, containing an alternate arrangement of a bis(terpyridine)ruthenium(II) moiety and a l-leucine residue, were synthesized and characterized by 1H NMR, UV, CD, and electrochemical properties. The intensity of CD spectra per ruthenium unit increased with the elongation of the peptide chain. 1H NMR analysis of a tetramer indicated the right-handed helical structure in acetonitrile.     

Bisthioxanthylidene biscrown ethers as potential stereodivergent chiral ligands

The concept of bisthioxanthylidene biscrown ethers as potential stereodivergent chiral ligands in asymmetric synthesis is introduced. Substituted bisthioxanthylidenes may be chiral and can exist as stable enantiomers due to their folded structure. As a result, both a right-handed helix (P) and left-handed helix (M) are present in this type of molecule. This offers the unique possibility to construct two crown ether moieties, attached to the same molecule, of which one exhibits (P)-helicity and the other (M)-helicity. When the crown ether moieties differ in size they can be complexed selectively with a base containing a cation of appropriate diameter. In this manner the (P)-helix and the (M)-helix can be activated selectively to serve as a chiral environment for base catalyzed asymmetric synthesis. Thus, we envisioned the new concept of a single chiral ligand to separately synthesize two enantiomers of a chiral product just by varying the added base. For this purpose, four new bisthioxanthylidene monocrown ethers and two new bisthioxanthylidene biscrown ethers were synthesized. Two biscrowns and two monocrowns were separated into their respective enantiomers (HPLC) and optical data (UV and CD) were collected to ensure stability of enantiomers at ambient temperatures. Ion complexation of one mono- and two biscrown ethers with potassium and sodium cations was investigated.     

Pseudohelical and helical primary structures of 1,2-spiroannelated four- and five-membered rings: syntheses and chiroptical properties

The pseudohelical hydrocarbons (R)-6, (S)-7, and (R)-8 and the helical hydrocarbon (P)-9, formally derived from the helical hydrocarbon (P)-4 by stepwise replacement of each of the four-membered rings by a five-membered ring, have been prepared. Their optical rotations vary systematically, both in magnitude and sign. Of the extremes, (P)-4 represents the usual case of a right-handed dextrorotatory helix, while (P)-9 represents the unusual case of a right-handed levorotatory helix. To rationalize these facts, DFT calculations of the rotatory power of (P)-helices of three-, four-, and five-membered rings have been performed. The results show a very good agreement with the experimental data for the rigid helices of three-membered rings and always show the correct sign and order of magnitude for the flexible helices of four- and five-membered rings for which Boltzmann-averaged optical rotations of up to six conformers had to be used. Within the conformers of the latter, a set of large dihedral angles for the bonds of the inner sphere correspond to a high specific rotation, and a set of small dihedral angles correspond to a low specific rotation. As a consequence, the Boltzmann-averaged values markedly depend on the geometry and weight of the conformers involved.     

SYNTHESIS OF AN EPOXY-TERMINATED HYPERBRANCHED AROMATIC POLYESTER

An epoxy-terminated hyperbranched aromatic polyester (P3) was synthesized from a hyperbranched aromaticpolyester containing carboxylic acid end groups (P1), which was derived from the condensation polymerization of the AB_2monomer, 5-acetoxyisophthalic acid. Polymer P1 was converted into the polymeric acid chloride by reaction with thionylchloride. The acid chloride was reacted with ethanol and glycidol to form a poly(ethyl ester) (P2) and an epoxy terminatedmaterial (P3), respectively. The reaction conditions in each step of these processes had to be controlled very carefully toavoid unwanted cross-linking reactions. The characterization of products and intermediates, including molecular weightdistributions and thermal properties, are reported.     

The structure of a TNA-TNA complex in solution: NMR study of the octamer duplex derived from alpha-(L)-threofuranosyl-(3'-2')-CGAATTCG

TNA (alpha-( l)-threofuranosyl-(3'-2') nucleic acid) is a nucleic acid in which the ribofuranose building block of the natural nucleic acid RNA is replaced by the tetrofuranose alpha-( l)-threose. This shortens the repetitive unit of the backbone by one bond as compared to the natural systems. Among the alternative nucleic acid structures studied so far in our laboratories in the etiological context, TNA is the only one that exhibits Watson-Crick pairing not only with itself but also with DNA and, even more strongly, with RNA. Using NMR spectroscopy, we have determined the structure of a duplex consisting entirely of TNA nucleotides. The TNA octamer (3'-2')-CGAATTCG forms a right-handed double helix with antiparallel strands paired according to the Watson-Crick mode. The dominant conformation of the sugar units has the 2'- and 3'-phosphodiester substituents in quasi-diaxial position and corresponds to a 4'-exo puckering. With 5.85 A, the average sequential P i -P i+1 distances of TNA are shorter than for A-type DNA (6.2 A). The helix parameters, in particular the slide and x-displacement, as well as the shallow and wide minor groove, place the TNA duplex in the structural vicinity of A-type DNA and RNA.     

Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility

Developed in the early 1990s, peptide nucleic acid (PNA) has emerged as a promising class of nucleic acid mimic because of its strong binding affinity and sequence selectivity toward DNA and RNA and resistance to enzymatic degradation by proteases and nucleases; however, the main drawbacks, as compared to other classes of oligonucleotides, are water solubility and biocompatibility. Herein we show that installation of a relatively small, hydrophilic (R)-diethylene glycol ("miniPEG", R-MP) unit at the γ-backbone transforms a randomly folded PNA into a right-handed helix. Synthesis of optically pure (R-MP)γPNA monomers is described, which can be accomplished in a few simple steps from a commercially available and relatively cheap Boc-l-serine. Once synthesized, (R-MP)γPNA oligomers are preorganized into a right-handed helix, hybridize to DNA and RNA with greater affinity and sequence selectivity, and are more water soluble and less aggregating than the parental PNA oligomers. The results presented herein have important implications for the future design and application of PNA in biology, biotechnology, and medicine, as well as in other disciplines, including drug discovery and molecular engineering.     

Effect of Molecular Structure on Complexation Between Acidic- and Basic-Polypeptides in Solution

Abstract

Interpolymer complex formation between basic polypeptides, poly(L- proline) Form I [PLP(I)], Form II [PLP(II)] and poly-4-hydroxy-L-proline (PHLP), and acidic polypeptides, poly(L-glutamic acid) (PLGA), poly(D- glutamic acid) (PDGA) and poly(L-aspartic acid) (PLAA), has been studied in water-methanol (1:2 v/v) mixed-solvent by viscometry, potentiometry, light scattering and circular dichroism (CD) measurements. It has been found that polymer complexes between basic- and acidic- polypeptides are formed via hydrogen bonding with a stoichiometric ratio of basic/acidic polypeptides =1:2 (in unit mole ratio) and that PLP(II) forms polymer complex more favorably with PLGA than with PLAA, and the complex of PLP(II) with PLGA is also more favorable than the complex formation of PHLP with PLGA. In addition, the complex formation is highly dependent on the conformation, especially the optical structure of the component polymers, i.e., the stereoselective complexation is observed. The PLGA having a right-handed helix at pH 3.2 formed the complex favorably and quickly with left-handed helix PLP(II), whereas PDGA having a left-handed helix at pH 3.2 favorably formed the complex with right-handed helix PLP(I).     

Helical structures of N-alkylated poly(p-benzamide)s

Poly(p-benzamide)s 1 bearing a chiral side chain on the nitrogen atom were synthesized by chain-growth polycondensation methodology. The polyamides exhibited well-defined molecular weights with narrow polydispersities. Solutions of the polyamides in several organic solvents (CH(3)CN, CHCl(3), and CH(3)OH) showed dispersion type CD signals characteristic of coupled-oscillator and much larger as compared with the corresponding monomer. The CD signals were dependent on the temperature and molecular weight of the polyamides but independent of the solvent, as far as examined. An exciton model analysis of the absorption and CD spectra provided a clear-cut picture for the secondary structure of these polyamides in solution that the N-alkylated poly(p-benzamide)s possess a right-handed helical conformation ((P)-helix). In the solid states, the results of X-ray crystallographic analysis of 4-(methylamino)benzoic acid oligomers substantiated that they have a helical conformation with three monomer units per turn.     

Palladium(ii) driven self-assembly of a saturated quadruple-stranded metallo helicate

Complexation of the bridging bidentate ligand N,N'-(pyridine-2,6-diyl)dinicotinamide, L with palladium(ii) resulted in a single discrete M(2)L(4) self-assembly, 1, in a quantitative manner. The entropically-controlled assembly of 1 resulted in a rare saturated, quadruple-stranded metallo-helicate, in which both the left-handed (M) and right-handed (P) helicates exist in the crystal structure.     

Expanding the conformational pool of cis-beta-sugar amino acid: accommodation of beta-hGly motif in robust 14-helix

Tendencies of forming stable helices of heterooligomers composed of alternating rigid cis-beta-sugar amino acid and flexible beta-hGly motifs have been investigated, using a combination of molecular mechanics, CD, FT-IR, and NMR techniques. The results show that the solution structures of these oligomers exist as robust right-handed 14-helices. Here, we examine the role of conformationally rigid cis-beta-sugar amino acid in preorganizing the conformation of beta-hGly to form the 14-helix. Our findings also show that a right-handed 14-helix can be formed with as few as four properly sequenced heterogeneous residues. These results represent the expansion of the conformational pool of sugar amino acid in the design of well-folded 14-helices, which can be used to develop beta-peptides endowed with biological activity.