Inclusion Compounds Formed from N,N-bis(2-hydroxybenzyl)alkylamine Derivatives and Transition Metal Ions via Molecular Assembly

A series of N,N-bis(2-hydroxybenzyl)alkylamine derivatives (1–5) have been found to form host–guest compounds with transition metal ions. The inclusion phenomena in solution are confirmed from the new peak at 415?nm observed by UV-Vis (ultraviolet-visible) spectroscopy and the aromatic and methylene peak shifts observed by ¹H NMR (proton nuclear magnetic resonance) spectroscopy. Comparative studies on 1–5 by liquid–liquid extraction studies suggest that the bulky group at the aza position of the derivatives obstructs the ion interaction resulting in the decrease in ion extraction ability. Inclusion depends on the interaction of the transition metal ions with the compounds 1–5 at the aza and hydroxyl groups as identified by the two-dimensional nuclear Overhauser enhancement technique (¹H–¹H NOESY). The results from Job's plot and electrospray ionization mass spectroscopy (ESIMS) imply molecular assembly of the host–guest system in a 2:1 ratio. Comparative studies among different ions, i.e., Cu²⁺, Zn²⁺ and Cd²⁺ suggest that the host–guest formation is effective when electron sharing is possible through the outer orbital of the transition metal ions. In the case of inclusion in the solid state, the FTIR (Fourier transform infrared) spectra show the changes in vibrational mode of the functional groups in host molecules whereas the X-ray diffraction (XRD) patterns suggest a change in the packing structure of the host molecules. After host–guest formation, the thermal stability of the host molecules decreases as a result of the change in the packing structure from a hydrogen-bonded network to one of ionic interaction with the guest.     

氨基甲酸酯型脱氧胆酸分子钳对中性分子的识别性能研究

利用差紫外光谱法考察了新型分子钳1～6对苯胺、对硝基苯胺、对甲氧基苯胺等中性分子的识别性能, 测定了25 ℃下, 在CHCl₃中主客体间的结合常数(K_a)和自由能变化(ΔG⁰). 结果表明, 所有分子钳主体对所考察的客体分子显示良好的识别作用, 主客体间形成1∶1型主客体络合物. 识别作用的主要推动力为多重氢键和π-π重叠等的作用. 讨论了主客体间形状、大小匹配和几何互补及识别模式等因素对识别能力的影响, 并利用核磁共振氢谱与计算机模拟作为辅助手段对实验结果进行了解释.     

芳酰胺-吖啶分子钳对中性分子的识别性能. II. 新型吖啶类分子钳的研究

采用差紫外谱法研究了新型芳酰胺-吖啶分子钳(1～7)对苯胺、苯二胺(邻, 间, 对)等中性分子的识别性能. 测定了结合常数(K_a)和自由能变化(ΔG°), 结果表明, 所有的分子钳受体与所考察的客体分子均形成1∶1型超分子配合物. 识别作用的主要推动力为多重氢键、van der Waals等的协同作用. 主客体间尺寸/形状匹配、几何互补等因素对识别性能均有重要的影响. 利用核磁氢谱与计算机模拟作为辅助手段对主要的实验结果与现象进行了解释.     

Host–Guest Interactions of Phosphorescent Molecular Tweezers Based on an Alkynylplatinum(II) Terpyridine System with Polyaromatic Hydrocarbons

Host–guest interactions of a molecular tweezer complex 1 with various planar organic molecules including polyaromatic hydrocarbons (PAHs) were investigated by 1D and 2D ¹H NMR spectroscopy, UV/Vis absorption and emission titration studies. 2D and DOSY NMR spectroscopies support the sandwiched binding mode based on 1:1 host–guest interactions. The binding constants (K_S) of complex 1 for various PAHs were determined by NMR titration studies and the values were found to span up to an order of 10⁴ M ^?1 for coronene to no observable interaction for benzene, indicating that the π‐surface area is important for such host–guest interactions. The substituent effect on the host–guest interaction based on the guest series of 9‐substituted anthracenes was also studied. In general, a stronger interaction was observed for the anthracene guest with electron‐donating groups, although steric and π‐conjugation factors cannot be completely excluded. The photophysical responses of complex 1 upon addition of various PAHs were measured by UV/Vis and emission titration studies. The UV/Vis absorption spectra were found to show a drop in absorbance of the metal‐to‐ligand charge‐transfer (MLCT) and ligand‐to‐ligand charge‐transfer (LLCT) admixture band upon addition of various guest molecules to 1 , whereas the emission behavior was found to change differently depending on the guest molecules, showing emission enhancement and/or quenching. It was found that emission quenching occurred either via energy transfer or electron transfer pathway or both, while emission enhancement was caused by the increase in rigidity of complex 1 as a result of host–guest interaction.     

A New Functional Cyclophane Host. Synthesis, Complex Formation and Crystal Structures of Three Inclusion Compounds

A new macrocyclic host compound 2 having an octamethylsubstituted cyclophane structure with two intra-annular carboxylic acid functions has beensynthesized. The properties of crystalline inclusion formation are studied and X-ray crystalstructures of three inclusion complexes including acetic acid, propionic acid and acetone asthe guest molecules are reported. Inter-host channel formation with complexed guest moleculesaccommodated into the channels are typical features of the acetic acid and acetone 1 : 4 (host : guest) stoichiometric complexes being also hydrated species, while the propionicacid 1 : 2 complex is of the close packing type containing no additional water molecules.Systems of hydrogen bonds involving the host and guest functional groups are common toall structures. In the case of the acetic acid inclusion compound, a complex supramolecularhydrogen-bonded array comprising a bordering tricyclic assembly of eight molecular species exists.     

环双(对-蒽基-对草快)的分子识别与谱学性质

环双(对-蒽基-对草快)是一种新型的缺电子大环仿生主体, 分子识别是其最重要的应用之一. 考察主体对一系列客体分子如水、氨、醇及杂环等的识别能力, 用密度泛函理论(DFT)中的B3LYP/3-21G基组对主客体复合物的结构进行优化. 在B3LYP/6-31G(d)水平上进行单点能计算, 校正后得到复合物的结合能. 用B3LYP/3-21G方法计算13C和3He化学位移. 结果表明, 主体对客体分子的识别主要靠客体上的杂原子与主体上的氢原子之间的氢键进行. 复合物的稳定化能受氢键的数目和距离影响. 氢键的形成导致部分复合物LUMO与HOMO能隙增大, 同时导致与氢键相连的C—H键上C原子的化学位移向低场移动. 复合物的芳香性与其结合能的大小及结合方式有关. 主体的芳香性因其与客体之间的弱相互作用而提高, 但太强的相互作用及客体在主体空腔内都将影响主体的环电流, 从而削弱其芳香性.     

Kinetic and thermodynamic inclusion complexes of symmetric teramethyl-substituted cucurbit[6]uril with HCl salts of N,N′-bis(pyridylmethyl)-1,6-hexanediamine

The host–guest interaction of symmetrical α,α′,δ,δ′-tetramethyl-cucurbit[6]uril (TMeQ[6]) with the hydrochloride salts of N,N′-bis(4-pyridylmethyl)-1,6-hexanediamine (P6), N,N′-bis(3-pyridyl-methyl)-1,6-hexanediamine (M6) and N,N′-bis(2-pyridylmethyl)-1,6-hexanediamine (O6) was investigated via single crystal X-ray diffraction, ¹H NMR spectroscopy, electronic absorption spectroscopy and fluorescence spectroscopy. Single crystal X-ray diffraction showed that the hexyl moiety of P6 or M6 was incorporated in the cavity of TMeQ[6], while the two pyridylmethyl moieties of O6 were incorporated in the TMeQ[6] cavity in the solid state. The ¹H NMR results in aqueous solution revealed that the TMeQ[6]-P6 and TMeQ[6]-M6 host–guest interaction systems produce a kinetic dumbbell-shaped inclusion complex at the initial stage and then an equilibrium pseudorotaxane-shaped inclusion complex as the only product after heating. However, only the pseudorotaxane-shaped inclusion complex was observed for the TMeQ[6]-O6 host–guest interaction system. Aqueous absorption spectrophotometric analysis showed that the dumbbell-shaped inclusion complexes were stable at pH 5.6, had a host–guest ratio of 2:1 and formed quantitatively at ～10¹¹ l²/mol² for the TMeQ[6]-M6 and TMeQ[6]-O6 systems. The transformation from dumbbell to pseudorotaxane-shaped inclusion complexes for the TMeQ[6]-P6 and TMeQ[6]-M6 host–guest systems yielded activation energies of 59.35 ± 1.55 and 78.7 ± 3.45 kJ/mol, respectively. The pseudorotaxane-shaped inclusion complexes were stable at pH 5.6, had a host–guest ratio of 1:1 and formed quantitatively at ～10⁷ l/mol for the TMeQ[6]-M6 and TMeQ[6]-P6 systems.     

How important is the dispersion interaction for cyclobis(paraquat‐p‐phenylene)‐based molecular “shuttles”? A theoretical study

Inclusion complexes of cyclobis(paraquat‐p‐phenylene) and various aromatic molecules in their neutral and oxidized form were studied at the LMP2/6‐311+G**//BHandHLYP/6‐31G* level of theory, which represents the highest level theoretical study to date for these complexes. The results show that it is dispersion interaction that contributes most to the binding energy. One electron oxidation of a guest molecule leads to complete dissociation of inclusion complex generating strong repulsion potential between guest and host molecules. Electrostatic interactions also can play an important role, provided the guest molecule has a dipole moment; however, dispersion interactions always dominate in binding energy. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Enantiodiscrimination of equol in β-cyclodextrin: an experimental and computational study

The interaction between the equol enantiomers and β -cyclodextrin is studied by molecular mechanics and molecular dynamics calculations. The chromatographic retention order is determined by these theoretical methods and compared with experimental findings. In the molecular mechanics calculations, the simultaneous relaxation of the host and the guest molecules is allowed, both in a vacuum and in aqueous solution. In the molecular dynamics calculations, the interaction energy between each enantiomer and the cavity is determined carrying out a simulation of 12 trajectories with different initial conditions at constant temperature (293 K), and minimising the energy of the structures extracted along the trajectories. To determine the preferential binding site and orientation of each guest molecule, the numerical density of presence in a volume element is calculated and compared with regions of maximum enantioselectivity. The more stable complex predicted in both cases is formed with R-equol, in agreement with experimental results.     

Host Perturbation in a β‐Hydroquinone Clathrate Studied by Combined X‐ray/Neutron Charge‐Density Analysis: Implications for Molecular Inclusion in Supramolecular Entities

X‐ray/neutron (X/N) diffraction data measured at very low temperature (15 K) in conjunction with ab initio theoretical calculations were used to model the crystal charge density (CD) of the host–guest complex of hydroquinone (HQ) and acetonitrile. Due to pseudosymmetry, information about the ordering of the acetonitrile molecules within the HQ cavities is present only in almost extinct, very weak diffraction data, which cannot be measured with sufficient accuracy even by using the brightest X‐ray and neutron sources available, and the CD model of the guest molecule was ultimately based on theoretical calculations. On the other hand, the CD of the HQ host structure is well determined by the experimental data. The neutron diffraction data provide hydrogen anisotropic thermal parameters and positions, which are important to obtain a reliable CD for this light‐atom‐only crystal. Atomic displacement parameters obtained independently from the X‐ray and neutron diffraction data show excellent agreement with a |ΔU| value of 0.00058 Ų indicating outstanding data quality. The CD and especially the derived electrostatic properties clearly reveal increased polarization of the HQ molecules in the host–guest complex compared with the HQ molecules in the empty HQ apohost crystal structure. It was found that the origin of the increased polarization is inclusion of the acetonitrile molecule, whereas the change in geometry of the HQ host structure following inclusion of the guest has very little effect on the electrostatic potential. The fact that guest inclusion has a profound effect on the electrostatic potential suggests that nonpolarizable force fields may be unsuitable for molecular dynamics simulations of host–guest interaction (e.g., in protein–drug complexes), at least for polar molecules.     

Encapsulation of adefovir bis(l-leucine propyl)ester pro-virucide in cucurbit[7]uril and its activity against tobacco mosaic virus

The interaction of cucurbit[7]uril (Q[7]) with a pro-virucide, adefovir bis(l-leucine propyl)ester (PMEA-Leu) in aqueous solutions and in solid state was studied by ¹H NMR, UV absorption spectroscopy, fluorescence and IR spectroscopy. The ¹H NMR revealed that the leucine propyl moiety of the compound could be entrapped in the cavity of the host Q[7], and the other moiety except for leucine propyl moieties, including aminopurine, was probably located at the portal area of Q[7]. Absorption and fluorescence spectroscopy proved that the interaction of Q[7] with PMEA-Leu led to the formation of host–guest inclusion complexes (2:1) that were controlled by the concentration of the host Q[7]. Formation of the inclusion complex between Q[7] and PMEA-Leu was confirmed by IR spectroscopy in solid state. In addition, deliquescent stability studies indicated that the moisture stability of the host–guest complex was significantly enhanced. The phenomenon was explained by the fact that the formation of solid inclusion complexes can prevent the compounds from absorbing water. Finally, bioactivity of PMEA-Leu and its inclusion complex against tobacco mosaic virus (TMV) was tested. The compound PMEA-Leu and its inclusion complexes showed some inhibitory activity against TMV at 500 μg/ml in vivo.     

Crystalline complexes of N,N'-ditritylurea (DTU) and N-tritylurea (NTU) hosts with molecular guests

This paper reports crystalline complexes of the new hosts N,N'-ditritylurea (DTU) and N-tritylurea (NTU) with various uncharged molecular guests. The crystal structures of the following complexes were elucidated by single crystal X-ray diffraction analysis at 115^oK: (I) 1:1 DTU-propanamide — space group C2/c, a=15.839Å, b=9.088Å, c=24.584Å, =111.05^o, Z=4; (II) 1:1 DTU-ethyl N-acetylglycinate — space group P1, a=9.010Å, b=10.800Å, c=19.810 Å, =105.29^o =94.33^o, =93.03^o, Z=2; (III) 2:1 NTU-N, N-dimethylformamide — space group Cc, a=29.614Å, b=8.906Å, c=16.127Å, =121.04^o, Z=4. The three crystal structures are stabilized mainly by a cooperative effect of hydrogen bonding between amide fragments displaced along the shortest axis of each crystal. This interaction occurs between host and guest in complexes I and II, and between host and host in complex III. The latter also represents a cage-type clathrate in which the guest molecules are accommodated in voids between the hydrophobic fragments of four neighboring NTU hosts. On the other hand, complexes of DTU are characterized by a more specific interaction between the two components, each guest molecule being inserted between two adjacent hosts (related by translation) and strongly bound to them via hydrogen bridges. These results illustrate a useful concept in the design of molecular species which can be potential hosts upon crystallization with neutral molecular guests. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82022 (7 pages).     

β-Cyclodextrin Complexes of Benzaldehyde,Vanillin and Cinnamaldehyde: A Raman Spectroscopic Study1

Abstract

Raman spectra of benzaldehyde, vanillin and trans-cinnamaldehyde, and of their complexes in β-cyclodextrin are presented and discussed. The guest molecules provide both an aromatic ring for privileged interaction with the cyclodextrin cavity, and characteristic vibrations (e.g., vC=O, vC=C, vCC? (?=phenyl), vC-H?) with group frequencies in spectral regions free from cyclodextrin bands which are useful for probing the guest perturbed by complex formation with β-cyclodextrin. In particular, the C=O bond is shown to be a good vibrational spectroscopic probe to monitor the effects of both the medium, through its dielectric constant, and of specific interactions, namely of the hydrogen bonding type. The first of these effects is evaluated theoretically and a Kirkwood-Bauer-Magat plot for benzaldehyde is used to estimate the effective dielectric constant for the guest in the benzaldehyde-β-cyclodextrin complex. The above mentioned Raman spectroscopic results are interpreted and discussed.     

Electrospray‐Ionization Mass Spectrometry for Screening the Specificity and Stability of Single‐Stranded‐DNA Templated Self‐Assemblies

Supramolecular complexes consisting of a single‐stranded oligothymine ( dTn ) as the host template and an array of guest molecules equipped with a complementary diaminotriazine hydrogen‐bonding unit have been studied with electrospray‐ionization mass spectrometry (ESI‐MS). In this hybrid construct, a supramolecular stack of guest molecules is hydrogen bonded to dTn . By changing the hydrogen‐bonding motif of the DNA host template or the guest molecules, selective hydrogen bonding was proven. We were able to detect single‐stranded‐DNA (ssDNA)–guest complexes for strands with lengths of up to 20 bases, in which the highest complex mass detected was 15 kDa; these complexes constitute 20‐component self‐assembled objects. Gas‐phase breakdown experiments on single‐ and multiple‐guest–DNA assemblies gave qualitative information on the fragmentation pathways and the relative complex stabilities. We found that the guest molecules are removed from the template one by one in a highly controlled way. The stabilities of the complexes depend mainly on the molecular weight of the guest molecules, a fact suggesting that the complexes collapse in the gas phase. By mixing two different guests with the ssDNA template, a multicomponent dynamic library can be created. Our results demonstrate that ESI‐MS is a powerful tool to analyze supramolecular ssDNA complexes in great detail.     

The structure - properties relations in the clathrates of N1 (NCS)2 (4-methylpyridine)4

The Ni(NCS)₂(4-methylpyridine)₄ molecule shows significant confomational flexibility of the four piooline and the two isothiocyanate ligands. Both intramolecular non-bonded energy calculations and x-ray crystal structures support the idea that the host molecule may adopt different conformations (molecular shape) in order to bind, in clathrate formation, guest molecules of different shape and size. This versatility enables the Ni(NCS)₂(4-methylpyridine)₄ complex to form many different crystal structures able to absorb both small molecules, e.g. noble gases, and relatively large condensed aromatic hydrocarbons. The type of the crystalline structure formed defines “primary” properties of the clathrate. Secondary effects are observed when varying lattice parameters of the host structure (dilatation - contraction) by introducing guest component of suitable composition.     

Studies on hydroxy inclusion complexes. I. Host-guest interaction of the molecular complexes of 9-hydroxy-9-(1-propynyl) fluorene and 1,1-Bis (2,4-dimethylphenyl)-2-butyn-1-ol with water,methanol, ethanol,andn-propanol

Molecular inclusion by hydroxy host systems (9-hydroxy-9-(1-propynyl)fluorene+guest and 1,1-bis(2,4-dimethylphenyl)-2-butyn-1-ol+guest) has been investigated by using an empirical potential function. Water, methanol, ethanol, andn-propanol have been employed as guest molecules and their relative stabilities are considered. Alcohol is found to be more suitable than water as a guest molecule in the two tested host molecules. It is also found that the nonbonded interaction is the most important factor in determining the relative stabilities of hydroxy host systems.     

Single-crystal-to-single-crystal Transformation of the Dichloromethane Solvate of the Shiff Base Manganese(III) Complex to a Solvent Free Material

The chloride complex of Mn(III)with an optically active Schiff base derived from3,5-tert-butyl-salicyl aldehyde and(1R,3S)-1,2,2,-trimethylcyclopentane-1,3-diaminecrystallizes as a 1 : 1 solvate (I) withCH₂Cl₂ and transforms at room temperature toa solvent-free compound (II) without destructionof the crystals. Two X-ray diffraction experimentscarried out on the same crystal at 120 K revealed thatthe guest CH₂Cl₂ molecules are completelyenclosed in the host matrix and that drasticconformational changes of the complex molecules occurduring removal of solvent. A possible mechanism of thecrystal transformation is disscused. The spectralevidence on association of the metal complex withdichloromethane in solution are demonstrated.     

Molecular Recognition by Cyclophane/Guanidinium Supramolecular Receptor Embedded at the Air-Water Interface

In order to develop a supramolecular receptor through a self-assembling process, a site-specific host and an inclusion-type host were mixed as a Langmuir monolayer, and guest binding and pressure-induced fluorescence emission were investigated. A guanidinium amphiphile and several cyclophanes carrying hydrophobic moieties were used as the host molecules; molecular recognition of an aqueous fluorescent guest, 6-p-toluidino-2-naphthalenesulfonic acid (TNS) by binary mixed receptor monolayers was evaluated by a surface pressure-molecular area (π-A) isotherm and a surface fluorescence measurement. An apparent increase in fluorescence intensity was observed when the mixed monolayers of the guanidinium and cyclophane amphiphiles were compressed on an aqueous TNS solution. In contrast, single-component monolayers of the guanidinium or the cyclophane did not show a significant increase in fluorescence emission. In the mixed monolayers, the guest TNS would be bound to the interface by strong electrostatic interaction with the guanidinium, and inclusion of the formed complex probably suppresses the quenching effect in polar medium and/or self-quenching. Experiments with various mixing ratios of these components suggest selective formation of an equimolar cooperative receptor of the guanidinium and the cyclophane. Investigation of the cyclophane structures by fluorescence emission and a competitive binding experiment with another guest were also carried out.     

Complexation of neurotransmitters ‒ dopamine,serotonin and melatonin ‒ with a DTPA-based cyclophane of high rigidity: 1H NMR shift and line-broadening

The ¹H NMR signals of the titled neurotransmitters undergo up-field shift accompanied by line-broadening in NMR titration with the DTPA-based cyclophane at pD 7.3; the cyclophane consists of a 4,4′-bis(1,1′-biphenyl-4,4′-dihydroxy)dianiline unit cyclised by a DTPA (diethylenetriaminepentaacetate) group through two amide linkages. Changes in chemical shifts of dopamine indicate the formation of a 1:1 complex with the formation constant K₁ 400 M^?1; the complex of serotonin is likely to form a 2:1 host?guest complex with β₂ ≈ 10⁵ M^?2; melatonin does not form a complex with definite stoichiometry. The primary binding forces in the dopamine and serotonin complexes are electrostatic interaction between cationic neurotransmitter and anionic cyclophane molecules, and the resulting ionic pairs are stabilised by encapsulation. The electrostatic interaction is weakened by electrolytes; in 0.1 M Trizma buffer, dopamine does not yield a definite complex, and serotonin forms a 1:1 complex with K₁ 80 M^?1. Extreme line-broadening of neurotransmitter signals suggests that the molecular motion of the guest molecule is slowed in the complex by interactions with the receptor molecule whose internal molecular motion is quenched partially. The high rigidity of the cyclophane enhances intermolecular interaction in the hydrophobic regions to prolong the lifetime of the complex.     

Free Energy Peturbation and Molecular Dynamics Simulation Studies on the Enantiomeric Discrimination of Amines by Dimethyldiketopyridino-18-Crown-6

Abstract

Discrimination of chiral amines by dimethyldiketopyridino-18-crown-6 (1) is studied by free energy peturbation (FEP) and molecular dynamics (MD) methods. 1 has two (S)-chiral centers and discriminates chiral amines through host-guest interactions. The optically active amines in this study are α-(1-naphthyl)ethylamine, methylbenzylamine, cyclohexylethylamine, and sec-butylamine. The trends in binding free energy differences obtained from FEP calculations were in excellent agreement with experimental results obtained in the gas phase. In order to explain the enantioselectivity of the host in terms of the host-guest interactions at the molecular level, we analyzed the structures generated by 10-ns MD simulations of host-guest complexes. The suggested chiral discrimination mechanism, the π-π interaction and the steric repulsion between the guest and the host, was verified by our MD simulation analysis.