Proposed Hydrogen-Bonding Index of Donor or Acceptor Reflecting Its Intrinsic Contribution to Hydrogen-Bonding Strength.

In this work, we tentatively propose that the hydrogen-bonding strength EHB (referring to the minimal hydrogen-bonding energy) and its corresponding hydrogen-bond (HB) distance (referring to the optimal HB distance dHB) for simple mono-HB systems have an exponential relationship on the basis of MP2 and DFT computational results. We take a step further and propose that the hydrogen-bonding indices of the donor (Idonor) and acceptor (Iacceptor), reflecting their intrinsic contributions to hydrogen-bonding strength, also have an exponential relation with the hypothetical effective hydrogen-bond radii of the donor (rdonor) and acceptor (racceptor), respectively. On the basis of extensive quantum-mechanical calculations, relevant assumptions about the hydrogen-bonding index are rationalized. Moreover, the hydrogen-bonding index is also suggested as an additional prefiltering criterion for virtual screening besides the widely accepted Lipinski's rule of five. Finally, a "Hydrogen-Bond Index Estimator (HBIE)" module has been implemented in our Visual Force Field Derivation Toolkit (VFFDT) program to approximately and rapidly estimate the hydrogen-bonding indices of any small molecules in batch and screen possible stronger donors or acceptors from the small-molecule database. To the best of our knowledge, the concept of the hydrogen-bonding index and its potential application are proposed here for the first time.

Foldamer-tuned switching kinetics and metastability of [2]rotaxanes.

Slip sliding away: foldamers can function as modular stoppers to regulate the slippage and de-slippage of pseudorotaxanes and the switching kinetics and metastability of bistable rotaxanes. By simply changing the solvent or the length of the hydrogen-bonded foldamer, the lifetime of the metastable co-conformation state can be increased dramatically, from several minutes to as long as several days.

Hydrogen bonding-directed quantitative self-assembly of cyclotriveratrylene capsules and their encapsulation of C60 and C70.

Under the direction of intramolecular three-center hydrogen bonding, two cyclotriveratrylene (CTV)-based capsules are assembled quantitatively from C(3)-symmetric CTV precursors by forming three imine bonds from arylamide-derived foldamer segments. (1)H and (13)C NMR and UV/vis experiments reveal that the capsules strongly encapsulate C(60) and C(70) in discrete solvents.

Vesicle self-assembly by tetrathiafulvalene derivatives in both polar and nonpolar solvents and pseudo-rotaxane mediated vesicle-to-microtube transformation.

This paper reports the self-assemblies of vesicles from two tetrathiafulvalene (TTF) derivatives (T1 and T2), that bear four or two amphiphilic side chains, in both polar and nonpolar solvents. The formation of vesicles is evidenced by scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) experiments, while the microstructural aspects of the vesicles are investigated by UV-vis, (1)H NMR, and high resolution TEM, which support a monolayer model for the vesicles. It is revealed that the formation of vesicles is driven by the combination of multiple noncovalent interactions, including pi-pi stacking, hydrogen-bonding, van der Waals force, and S...S interactions. It is also found that, in the presence of electron-deficient cyclobis(paraquat-p-phenylene) tetracation cyclophane, vesicles of T2 can transform into microtubes as a result of the formation of the pseudo[2]rotaxane between the TTF unit of T2 and the cyclophane. This process can be reversed by introducing pristine TTF into the solution of microtubes, due to release of T2 from the pseudo[2]rotaxane through the formation of a more stable complex between pristine TTF and tetracation cyclophane.

Folding of aromatic amide-based oligomers induced by benzene-1,3,5-tricarboxylate anion in DMSO.

In this paper, we describe the folding of a series of linear arylamide oligomers in DMSO that is induced by benzene-1,3,5-tricarboxylate anion. The oligomers are comprised of naphthalene-2,7-diamine and 1,3,5-benzenetricarboxylic acid segments with two (tert-butoxycarbonylamino) groups at the ends and two to four hydrophilic N,N-bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)amino groups at one side of the backbones. (2D NOESY) (1)H NMR, fluorescence and UV-vis studies indicate that the oligomers do not adopt defined conformations in DMSO but fold into compact structures in the presence of the anion. It is revealed that the folded conformation is induced by intermolecular hydrogen bonds between the amide and aromatic hydrogen atoms of the oligomers and the oxygen atoms of the anion. (1)H NMR and UV-vis titrations support a 1:1 binding stoichiometry, and the associated constants are determined, which are found to increase with the elongation of the oligomers.

A click chemistry approach for the synthesis of macrocycles from aryl amide-based precursors directed by hydrogen bonding.

This paper describes the synthesis of four aryl amide-based macrocycles through the 1 + 1 formation of two 1,2,3-triazole units by click chemistry. Two series of aryl amide-based precursors that bear two azide or acetylene units have been prepared. Intramolecular hydrogen bonding has been utilized to induce them to adopt a U-styled conformation, which remarkably promotes the macrocyclization of two structurally matched precursors.

Hydrogen-bonding-mediated dynamic covalent synthesis of macrocycles and capsules: new receptors for aliphatic ammonium ions and the formation of pseudo[3]rotaxanes.

This paper describes a novel, highly efficient approach to the self-assembly of monomacrocycles and two-layered capsules by using dynamic covalent chemistry. Intramolecular hydrogen-bonding was used to preorganize aromatic amide-based monomers that contain aldehyde and tert-butoxycarbonylamino units. As a result, in the presence of an excess of trifluoroacetic acid (TFA), four monomers could self-couple to produce macrocycles selectively through the formation of three imine or hydrazone bonds. Three dipodal precursors were also prepared by connecting two hydrogen-bonded segments with a flexible linker. In the presence of TFA, these precursors could also self-couple, leading to the exclusive formation of two-layered capsules. As a result of intramolecular hydrogen-bonding, all the macrocycles and capsules were stable in solution and could be purified by simple recrystallization. The new capsules were able to form complexes with linear propylenediammonium derivatives to give unique two-layered pseudo[3]rotaxanes.

Self-assembly of vesicles from amphiphilic aromatic amide-based oligomers.

A novel class of linear arylamide oligomers has been designed and synthesized from naphthalene-2,7-diamine and benzene-1,3,5-tricarboxylic acid segments. The molecules carry two (tert-butoxycarbonylamino) groups at the ends and one to three hydrophilic N,N-bis(2-(2-(2-methoxyethoxy)ethoxy)ethyl)amino groups at one side of the backbone. The oligomers self-assembled into vesicular structures in methanol as a result of ordered stacking of the oligomeric amide backbones, which were evidenced by SEM, AFM, TEM, and fluorescent micrography experiments. It was also found that the tert-butoxycarbonylamino groups at the ends played an important role in promoting the ordered stacking of the backbones. Structural factors that affected the self-assembly of the oligomers were investigated. A two-layer model that was supported by TEM has been proposed for the formation of the vesicular structures, which was driven by both the hydrogen bonding and aromatic stacking.

Cholesterol-appended aromatic imine organogelators: a case study of gelation-driven component selection.

This letter describes a novel approach for developing organogelators through the formation of reversible imine bonds from two molecular components and the enriching behavior of the gelating imines. Cholesterol-appended aniline 1 and 4-substituted benzaldehydes 2a-d did not gelate any solvents. Their condensation products, imines 3a-d, however, could gelate alcohols because of the enhanced stacking interaction of the imine unit. For a further component selectivity test, the reactions of the mixture of 1, 2b-d, and cholesterol-free aniline 7 (1:1:1) in different solvents were performed. The resulting imines were reduced to the corresponding amines and analyzed with 1H NMR. It was revealed that, for the reactions resulting in no formation of the gel phase, imines 8a-c formed from 2b-d and 7 were obtained as the major product (64-76%) and all of the reactions that led to the formation of the gel phase gave rise to 3b-d as the major product (55-61%).

Foldamer organogels: a circular dichroism study of glucose-mediated dynamic helicity induction and amplification.

This paper reports a systematic study of the dynamic process for the self-assembly of chiral organogels from achiral hydrogen bonded hydrazide foldamers by induction of chiral glucose. Six foldamers incorporated with six decyl chains and two benzene, naphthalene, anthracene, or pyrene units at the ends are revealed to strongly gelate apolar and polar solvents, including alkanes, arenes, esters, alcohols, and 1,4-dioxane. The gels are characterized by UV-vis, fluorescent, XRD, SEM, and AFM methods, based on which a dislocated "tail-to-tail" stacking pattern is proposed. Addition of octylated glucose considerably enhances the capacity of the foldamers to gelate apolar solvents due to strong complexation. The complexation also causes unique dynamic helicity induction in the gels, which is studied systematically by circular dichroism. The results are treated with the Avrami theory according to a reported method (J. Am. Chem. Soc. 2005, 127, 4336), which suggests that the gelation involves a nucleation-elongation mechanism. In addition, the "Sergeants and Soldiers" effect in the gel phase is also revealed.

Vesicles and organogels from foldamers: a solvent-modulated self-assembling process.

Nonamphiphilic, hydrogen-bonded hydrazide foldamers appended with four or six long flexible chains were revealed to spontaneously assemble to form vesicles in methanol and organogels in aliphatic hydrocarbons. SEM, AFM, TEM, DLS, and fluorescence microscopy were all used to identify the structures of the vesicles. It was proposed that intermolecular pi stacking of the folded frameworks and hydrogen bonding of the amide units in the appended chains induced the molecules to produce cylindrical aggregates. In polar methanol, these aggregates packed together to generate one-layered vesicles owing to hydrophobically induced entanglement of the peripheral chains, while in nonpolar hydrocarbons, the peripheral chains entwined across stacked cylinders to form three-dimensional networks and thus immobilize the liquid molecules.

Geometrical Preferences of the Hydrogen Bonds on Protein-Ligand Binding Interface Derived from Statistical Surveys and Quantum Mechanics Calculations.

We have conducted potential of mean force (PMF) analyses to derive the geometrical parameters of various types of hydrogen bonds on protein-ligand binding interface. Our PMF analyses are based on a set of 4535 high-quality protein-ligand complex structures, which are compiled through a systematic mining of the entire Protein Data Bank. Hydrogen bond donor and acceptor atoms are classified into several basic types. Both distance- and angle-dependent statistical potentials are derived for each donor-acceptor pair, from which distance and angle cutoffs are obtained in an objective, unambiguous manner. These donor-acceptor pairs are also studied by quantum mechanics (QM) calculations at the MP2/6-311++G** level on model molecules. Comparison of the outcomes of PMF analyses and QM calculations suggests that QM calculation may serve as an alternative approach for characterizing hydrogen bond geometry. Both of our PMF analyses and QM calculations indicate that C-H···O hydrogen bonds are relatively weak as compared to common hydrogen bonds formed between nitrogen and oxygen atoms. A survey on the protein-ligand complex structures in our data set has revealed that Cα-H···O hydrogen bonds observed in protein-ligand binding are frequently accompanied by bifurcate N-H···O hydrogen bonds. Thus, the Cα-H···O hydrogen bonds in such cases would better be interpreted as secondary interactions.

Diastereomeric recognition of chiral foldamer receptors for chiral glucoses.

[reaction: see text] Three chiral aromatic hydrazide foldamers have been designed and synthesized, in which two R- or S-proline units were incorporated at the terminals of their backbones. The 1H NMR, circular dichroism (CD), and fluorescent experiments and molecular dynamics simulations revealed that the foldamers adopted a chiral helical conformation and complexed alkylated glucoses in chloroform with a good diastereomeric selectivity.