Helical molecular programming: folding of oligopyridine-dicarboxamides into molecular single helices

Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyridinedicarbonyl units have been designed to self-organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric strand 15 have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X-ray diffraction analysis for four of these compounds. Helices from pentameric strands 12 and 14 extend over one turn, and helices from heptameric 20 and undecameric 15 species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation.     

Helical molecular duplex strands: multiple hydrogen-bond-mediated assembly of self-complementary oligomeric hydrazide derivatives

Careful examination of the X-ray structure of a ditopic hydrazide derivative 7 led to the concept that with malonyl groups as interhydrazide linkers hydrogen-bonding-mediated molecular duplex strands might be obtained. Complexation studies between 7, 8, and 9 confirmed this hypothesis. Two quadruple hydrogen-bonded heterodimers formed, in which spectator repulsive secondary electrostatic interaction was found to play an important role in determining the stability of the complexes. Extensive studies on 1-4 indicated that the hydrogen-bonding mode could persist in longer oligomeric hydrazide derivatives with chain extension from monomer to tetramer. Molecular duplex strands via two to fourteen interstrand hydrogen bonds were obtained. In addition to affecting the stability of the duplex strands, spectator repulsive secondary electrostatic interaction also played an important role in determining dynamic behavior of the duplex strands as exemplified by variable temperature (1)H NMR experiments. IR studies confirmed stronger hydrogen bonding in the longer oligomers. The assemblies of 1-4 on HOPG were also studied by STM technology. Molecular mechanical calculations further revealed double-helical structures for the longer oligomers. The results provide new opportunities for development of polymeric helical duplexes with well-defined structures.     

Assessing the mechanical properties of a molecular spring

We report on the dramatic effect of increasing helix diameter on the hybridization of oligopyridine-dicarboxamide strands into double helices. Upon replacing a single pyridine by a 1,8-diazaanthracene unit within an oligomeric strand, a 4.7 A enlargement of the helix diameter occurs parallel to the long anthracene axis. This structure change results in a spectacular stabilization of the double helical hybrids derived from these strands (factors of over 10(7)). Detailed investigations of the hybridization process using X-ray crystallography, NMR, fluorescence measurements and molecular mechanics calculations allowed us to assign the duplex stabilization to two enthalpic effects. First, the increase in diameter results in an augmented surface, involved in intermolecular pi-pi stacking. Second, the enlarged diameter leads to a lower tilt angle of the helical strand, with respect to the helix axis, which in turn results in smaller dihedral angles at the aryl-amide linkages and thus a considerably lowered enthalpic cost of the spring-like extension of the strands during the hybridization process. These results provide novel insights into how subtle tuning of molecular components may result in considerable and rationalizable changes in double helical supramolecular architectures.     

Diversity of interstrand π—π stacking motifs in the double helices of pyridinedicarboxamide oligomers

Winding of oligoamide strands of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid into molecular duplexes is illustrated by two new crystal structures of double helical dimers. The relative positions of the two strands within the double helices in these two structures are different; they also differ from the structures reported previously. Unlike the single helical structure of the monomeric strands, the double helical motif is not highly stable in the solid state. This implies that the interactions that lead to duplex formation are not directional. It suggests that the two strands have a significant motional freedom in the duplex.     

Double versus single helical structures of oligopyridine-dicarboxamide strands. Part 1: Effect of oligomer length

Oligoamides of 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid were previously shown to fold into single helical monomers and to hybridize into double helical dimers. A new series of these oligomers comprising 5 to 15 pyridine units, 4-decyloxy residues, and benzylcarbamate end groups were synthesized using a new convergent scheme that involves an early disymmetrization of the diamine and of the diacid. The hybridization of these compounds into double helices was studied by ¹H NMR spectroscopy in chloroform solutions at various temperatures. Somewhat unexpectedly, these studies revealed that dimerization increases with oligomer length up to a certain point, and then decreases down to undetectable levels for the longest strands. NMR studies show that both double helices and single helices become more stable when strand length increases. The measured values of enthalpy and entropy of hybridization for oligomers of various length show that the enthalpic gain constantly decreases with strand length. This can be interpreted as being the result of an increasing enthalpic price of the spring-like extension that the strand undergoes upon hybridization as its length increases. On the other hand, the entropic loss of hybridization also constantly decreases with strand length. Presumably, the helical preorganization of the monomers increases with strand length, which allows the longer strands to hybridize with a minimal loss of motional freedom, that is to say at a low entropic price. The competiton between these two factors results in a maximum of hybridization for the strands having an intermediate length.     

Phenanthroline dicarboxamide-based helical foldamers: stable helical structures in methanol

A series of new aromatic oligoamides 2-5 based on 1,10-phenanthroline diacid and o-phenylenediamine have been synthesized through a convergent segment coupling strategy. These oligomers can fold into well-defined helical structures in solution through intramolecular hydrogen bonds and aromatic stacking interactions, which has been established by 1H NMR, fluorescence, and UV/vis spectra. In particular, it was found that the oligomers were more favorable to fold into stable helical structures in methanol than in chloroform and dichloromethane. The helical foldamers formed in the solid state have been characterized by single-crystal X-ray diffraction analysis. The results showed that the high curvature of the strands led to one and a half turns for both 2 and 21, three turns for 4, and nearly four turns for 5.     

Dipeptide-induced chirality organization

This review describes an outline of dipeptide-induced chirality organization by using molecular scaffolds. A variety of ferrocene-dipeptide conjugates as bioorganometallics are designed to induce chirality-organized structures of peptides. The ferrocene serves as a reliable organometallic scaffold with a central reverse-turn unit for the construction of protein secondary structures via intramolecular hydrogen bondings, wherein the attached dipeptide strands are constrained within the appropriate dimensions. Another interesting feature of ferrocene-dipeptide conjugates is their strong tendency to self-assemble through contribution of available hydrogen bonding sites for helical architectures in solid states. Symmetrical introduction of two dipeptide chains into a urea molecular scaffold is performed to induce the formation of the chiral hydrogen-bonded duplex, wherein each hydrogen-bonded duplex is connected by continuous intermolecular hydrogen bonds to form a double helix-like arrangement.     

Dynamic chemical devices: generation of reversible extension/contraction molecular motion by ion-triggered single/double helix interconversion

The polyheterocyclic strands 1-H and 2-H adopt a helical shape enforced by the pyridine-pyrimidine helicity codon. The crystal structure of 2-H shows the formation of stacks of dimers of right- and left-handed individual helices. Treatment of 1-H and 2-H with silver triflate results in the generation of double-helical entities 1-DH and 2-DH, containing two strands and two silver ions. NMR studies and determination of the crystal structure of 2-DH indicate that the duplex is stabilized by coordination of each Ag(+) ion to two terminal bipyridine units, one from each strand, and by pronounced pi-pi stacking interactions between the internal heterocycles of the strands, yielding a very robust double helical structure. Reversible interconversion of the single and double helix may be achieved by addition of a cryptand capable of sequestering Ag(+) and releasing it by protonation. Thus, successive addition of acid and base leads to reversible interconversion between the shorter ( approximately 3.6 A) single helix and the longer ( approximately 10.3 A) double helix, resulting in the generation of pronounced extension/contraction motion. The system 1,2-H/1,2-DH represents a dynamic chemical device undergoing ionic modulation of reversible molecular mechanical motion fueled by acid/base neutralization.     

High-Affinity Hybridization of Complementary Aromatic Oligoamide Strands in Water

We prepared a series of water-soluble aromatic oligoamide sequences all composed of a segment prone to form a single helix and a segment prone to dimerize into a double helix. These sequences exclusively assemble as antiparallel duplexes. The modification of the duplex inner rim by varying the nature of the substituents borne by the aromatic monomers allowed us to identify sequences that can hybridize by combining two chemically different strands, with high affinity and complete selectivity in water. X-ray crystallography confirmed the expected antiparallel configuration of the duplexes whereas NMR spectroscopy and mass spectrometry allowed us to assess precisely the extent of the hybridization. The hybridization kinetics of the aromatic strands was shown to depend on both the nature of the substituents responsible for strand complementarity and the length of the aromatic strand. These results highlight the great potential of aromatic hetero-duplex as a tool to construct non-symmetrical dynamic supramolecular assemblies.     

Chalcogen-Bond-Induced Double Helix Based on Self-Assembly of a Small Planar Building Block

As a rule, helical structures at the molecular level are formed by non-planar units. This makes the design of helices, starting from planar building blocks via self-assembly, even more fascinating. Until now, however, this has only been achieved in rare cases, where hydrogen and halogen bonds were involved. Here, we show that the carbonyl-tellurium interaction motif is suitable to assemble even small planar units into helical structures in solid phase. We found two different types of helices: both single and double helices, depending on the substitution pattern. In the double helix, the strands are connected by additional Te⋅⋅⋅Te chalcogen bonds. In the case of the single helix, a spontaneous enantiomeric resolution occurs in the crystal. This underlines the potential of the carbonyl-tellurium chalcogen bond to generate complex three-dimensional patterns.     

Solution structure of a DNA duplex containing a biphenyl pair

Hydrogen-bonding and stacking interactions between nucleobases are considered to be the major noncovalent interactions that stabilize the DNA and RNA double helices. In recent work we found that one or multiple biphenyl pairs, devoid of any potential for hydrogen bond formation, can be introduced into a DNA double helix without loss of duplex stability. We hypothesized that interstrand stacking interactions of the biphenyl residues maintain duplex stability. Here we present an NMR structure of the decamer duplex d(GTGACXGCAG) d(CTGCYGTCAC) that contains one such X/Y biaryl pair. X represents a 3',5'-dinitrobiphenyl- and Y a 3',4'-dimethoxybiphenyl C-nucleoside unit. The experimentally determined solution structure shows a B-DNA duplex with a slight kink at the site of modification. The biphenyl groups are intercalated side by side as a pair between the natural base pairs and are stacked head to tail in van der Waals contact with each other. The first phenyl rings of the biphenyl units each show tight intrastrand stacking to their natural base neighbors on the 3'-side, thus strongly favoring one of two possible interstrand intercalation structures. In order to accommodate the biphenyl units in the duplex the helical pitch is widened while the helical twist at the site of modification is reduced. Interestingly, the biphenyl rings are not static in the duplex but are in dynamic motion even at 294 K.     

石油胶质结构性质的量子化学研究

采用量子化学AM1方法对石油胶质进行了优化计算，得到石油胶质单层结构SG、双层结构DG和三层结构TG的优化构型和分子间作用能。结果表明，石油胶质的稠环芳烃和脂环部分大体为平面结构，支链部分也伸展在平面上。分子中稠环、脂环和侧链中的C—C键长均分别比单独苯环、脂肪环和烷烃的C—C键短。侧链中的C—C键比芳环和脂环的C—C键弱，在催化剂的作用下将优先裂解。重叠形成DG和TG后，键长、键角和电荷略有变化。胶质分子的极性基团间存在氢键作用，DG和TG分子间的作用能分别为－22.8416kJ/mol和－43.8455kJ/mol。双层胶质DG和三层胶质TG结构的体积较大，难以扩散到分子筛催化剂的孔道内。     

Molecular electrotatic potential of a triple stranded helix: Poly(dT)·poly(dA)·poly(dT)

The molecular electrostatic potential of the triple helix poly(dT)·tpoly(dA)·poly(dT) is calculated, and the results are examined in relation to those obtained for its component double and single helical parts. For the double helix presenting the standard Watson–Crick hydrogen bonds, the deepest potentials are formed on the side of the major groove, a situation similar to that observed in the A-DNA duplex. For the double helix presenting Hoogsteen-type hydrogen bonds the deepest potentials lie in the major groove, on the side of the pyrimidine strand. In the triple helix the deepest potentials are located in the major groove in a narrow zone over the thymine bases of the Watson–Crick pair.     

Hybridization energies of double strands composed of DNA, RNA, PNA and LNA

The electronic properties of double strands composed of trimeric LNA, PNA, DNA and RNA single strands were investigated by density-functional molecular orbital calculations. The computed hybridization energies for the double strands involving PNA or LNA are larger than those for DNA-DNA and RNA-RNA. The larger stability is attributed to the presence of a larger positive charge of the hydrogen atoms contributing to the hydrogen bonds in the PNA-DNA and LNA-DNA double-strands. These results are comparable to the experimental finding that PNA and LNA single strands display high affinity toward a complementary DNA or RNA single strand.     

Dynamic decomposition/recombination of hydrogen bonds in molecular duplex strands

Dynamic decomposition/recombination of hydrogen bonds in the hydrazide based molecular duplex strands was explored by variable-temperature 1H NMR experiments. A shuttle-like dynamic process of the two constituent molecules of the duplex strands between two degenerate states was observed.     

Watson–Crick Base Pairing Controls Excited‐State Decay in Natural DNA

Excited‐state dynamics are essential to understanding the formation of DNA lesions induced by UV light. By using femtosecond IR spectroscopy, it was possible to determine the lifetimes of the excited states of all four bases in the double‐stranded environment of natural DNA. After UV excitation of the DNA duplex, we detected a concerted decay of base pairs connected by Watson–Crick hydrogen bonds. A comparison of single‐ and double‐stranded DNA showed that the reactive charge‐transfer states formed in the single strands are suppressed by base pairing in the duplex. The strong influence of the Watson–Crick hydrogen bonds indicates that proton transfer opens an efficient decay path in the duplex that prohibits the formation or reduces the lifetime of reactive charge‐transfer states.     

Highly effective acyclic carbohydrate receptors consisting of aminopyridine, imidazole, and indole recognition units

Neutral imidazole/aminopyridine- and indole/aminopyridine-based receptors, 1 and 2, have been established as highly effective and selective carbohydrate receptors. These receptors effectively recognise neutral carbohydrates through multiple interactions, including neutral hydrogen bonds and CH...pi interactions between the sugar CH groups and the aromatic rings of the receptors. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein-carbohydrate complexes. The formation of very strong complexes with beta-glucopyranoside 5, beta-maltoside 8, and alpha-maltoside 9 in organic media has been characterised by 1H NMR spectroscopy and confirmed by a second, independent technique, namely fluorescence spectroscopy. The syntheses, molecular-modelling studies, binding properties of the receptors 1 and 2 toward selected mono- and disaccharides as well as comparative binding studies with receptors 3 and 4 are described.     

Pressure effects on the structural,electronic, and optical properties of Sin@SWCNTs

Well‐ordered single, double/four parallel, three/four‐strands helical chains, and five‐strand helical chain with a single atom chain at the center of Si nanowires (NWs) inside single‐walled carbon nanotubes (Si_n@SWCNTs) are obtained by means of molecular dynamics. On the basis of these optimized structures, the structural evolution of Si_n@SWCNTs subjected to axial stress at low temperature is also investigated. Interestingly, the double parallel chains depart at the center and transform into two perpendicular parts, the helical shell transformed into chain, and the strand number of Si NWs increases during the stress load. Through analyzis of pair correlation function (PCF), the density of states (DOS), and the z‐axis polarized absorption spectra of Si_n@SWCNTs, we find that the behavior of Si_n@SWCNTs under stress strongly depends on SWCNTs' symmetry, diameter, as well as the shape of NWs, which provide valuable information for potential application in high pressure cases such as seabed cable. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009