Ammonium Guests Research Articles

A tryptophan-analog host whose interactions with ammonium ions in water are dominated by the hydrophobic effect

The binding of quaternary ammonium guests to a flexible, indole-based host has been studied in both aqueous and organic solvents. Binding was shown to depend strongly on the hydrophobic effect and less on the cation–π interaction.

Synthesis and structure of mono-bridged resorcinarene host: a ditopic receptor for ammonium guests

The synthesis and structural properties of tetramethoxy resorcinarene mono-crown-5 (1) are described. The binding characteristics of 1 toward acetylcholine and tetramethylammonium salts were investigated by 1H NMR titration. It was observed that the cavity of 1 provides a better fit to acetylcholine compared to the smaller tetramethylammonium cation, as acetylcholine is able to interact with both the crown ether moiety and the free hydroxyl groups of receptor 1 simultaneously.

Dynamic Combinatorial Discovery of a [2]-Catenane and its Guest-Induced Conversion into a Molecular Square Host

A simple water-soluble naphthalenedithiol building block is converted quantitatively into a series of octameric [2]-catenanes, composed of two interlocked molecular squares. When this mixture is re-equilibrated in the presence of an adamantyl ammonium guest, the catenanes disassemble into their macrocyclic components that bind the guest with nanomolar affinity in water.

Calix[6]arene Tris-carboxylic Acid Derivatives: X-ray and NMR Characterization of their Remarkable Host-guest Properties Toward Ammonium Ions

The ability of calix[6]arene tris-carboxylic acid derivatives to include ammonium guests has been investigated both in solution and in the solid state. NMR studies and crystallographic data showed that the highly flexible calix[6]arene structures can be shaped in a well defined cone conformation thanks to the formation of an ion-paired cap between the carboxylate groups of the calixarene and their ammonium counter-ions. The resulting supramolecular edifices exhibit remarkable host-guest properties toward ammonium ions even in polar and protic solvents. The recognition process has been rationalized in the solid state by the combination of hydrogen bonding, electrostatic and CH–π interactions, and a remarkable C 3-complementarity between the well-organized binding carboxylates of the host and the ammonium guest. Very interestingly, the endo-cavity complexation of large polycyclic ammonium ions as well as bioactive ammonium ions has been clearly demonstrated through NMR spectroscopy. Finally, the tuning of the nature of the ammonium ions involved in the supramolecular cap led to highly responsive molecular receptors.

Fluorescent studies of two new binaphthyl–azacrown–anthracene fluorophores with metal ions and chiral guests: dual fluorescent detection via binaphthyl and anthracene groups

Two new binaphthyl–azacrown–anthracene fluorophores were synthesized. These new fluorescent receptors exhibited large fluorescent changes with aqueous Hg 2+, Cu 2+ and Zn 2+. Interestingly, the fluorescent emissions from the binaphthyl and anthracene groups using different excitation wavelengths showed different patterns in the presence of metal ions. The chiral recognitions of these receptors with chiral ammonium guests were also examined.

The Effects of O-Substituents of Hexahomotrioxacalix[3]arene on Potentiometric Discrimination between Dopamine and Biological Organic/Inorganic Cations

As an interesting type of molecular recognition at a membrane surface, the tri-O-acetic acid ester (host 2) of hexahomotrioxacalix[3]arene, when incorporated into poly(vinyl chloride) (PVC) liquid membranes, displays a high potentiometric selectivity for dopamine over, not only other catecholamines (noradrenaline, adrenaline), but also quaternary ammonium guests (tetramethylammonium, choline, and acetylcholine) and inorganic cations (Na+, K+, NH4+). Interestingly, changes in membrane potential based on the host-guest complexation of host 2 that were observed dopamine/inorganic cation selectivity were not displayed by the related hosts 3 and 4, which contain amide substituents. This paper describes our efforts to separately estimate the two factors contributing to the dopamine selectivities, i.e., the guest lipophilicity factor and the host-guest complexation factor, in an attempt to understand the effects of the O-substituents of these hosts. The potentiometric experiments showed that, although the guests had roughly equal lipophilicity, the electromotive force (EMF) response for dopamine by host 2 was excellent. Furthermore, host 2 displayed ca. a 20-fold stronger complexation for dopamine, compared to noradrenaline, adrenaline, K+, and NH4+ cations. These results indicate that the high potentiometric selectivity of the ion-selective electrode for dopamine mainly reflect, not the guest lipophilicity factor but the host-guest complexation factor. On the other hand, host 3 displayed ca. a 3000-fold stronger binding to Na+ than dopamine, thus explaining the reasons for the lower dopamine-selectivities of host 3 compared to host 2. It is interesting to note that the high potentiometric selectivities for dopamine were displayed by not only host 2 but also host 5, regardless of the simple structure of the O-substituents.

X-ray Structure and Alkyl Ammonium Recognition of Quadruply Bridged Calix[6]arene:A Selective Inclusion of Primary Alkyl Ammonium with Calix[6]arene

Numerous attempts have been made to design new host systems which can selectively interact the target guest and perform intriguing molecular recognition processes. The selective recognition of many important biogenic amines is one of the fundamental research interests in the field of the biomimetic chemistry. Particularly, selective binding of organic ammonium guests attracts an important research interest due to the application of biological systems, which results in developing of many sophisticated host systems. Calixarenes present attractive possibilities in the hostguest chemistry as molecular frameworks for the preparation of conformationally preorganized polyfunctional derivatives, whose convergent ligating groups can act cooperatively to selectively bind ions or neutral molecules. Especially, the architecture of calixarenes is such that they also possess hydrophobic cavities generated by the aromatic walls of phenol residues, which are potentially useful for the inclusion of alkyl ammonium ions. Whereas the calix[4]arene cavity in the cone conformation is too narrow to accommodate even small amine salts, that of calix[6]arene is large enough to include small to medium-sized ammonium ions. The parent calix[6]arenes, however, are conformationally mobile. The most effective approach to make them immobile is to build a bridge at the lower or upper rim. Ever since Gutsche created the lower rim-bridged calix[6]arene in 1993, several lower rim-multibridged calix[6]arenes have been reported. Also the calix[6](aza)cryptand which has a tripodal poly-aza cap on the lower rim as a efficient host for small ammonium was reported by U. Darbost et al. The quadruply bridged calix[6]arene derivatives, which had been reported by our group, are also known for having a well-defined cavity capable of incorporating various cations. Here we report the X-ray structure of quadruply bridged calix[6]arene (3) and the binding properties for various alkylammonium picrates by the H NMR analysis. Binding properties also were analyzed from the X-ray structure and the NOE study.

Synthesis of Chiral Resorcinarene-based Hosts and a Mass Spectrometric Study of their Chemistry in Solution and the Gas Phase

The syntheses and characterization of new chiral tetrabenzoxazine and tetrakis-(dialkylaminomethyl) resorcinarenes can be achieved through the reaction of resorcinarene with chiral amines and formaldehyde. In order to examine their host–guest chemistry, chiral quaternary ammonium guests were synthesized by methylation of different amines and amino acid methyl esters through a reductive methylation followed by addition of methyl iodide. Subsequent anion exchange of the iodide against tetraphenylborate helps to improve solubility of the salts in organic solvents. After characterization in solution, mass spectrometry is used to examine the resorcinarenes’ chemistry in the gas phase. Interesting implications of the fragmentation behavior for their solution phase chemistry arise, for which a first example is presented. Ammonium ion binding is indicated by mass spectrometry. Nevertheless, chiral recognition between the chiral hosts and pseudoracemic 1:1 mixtures of appropriately deuterium-labeled chiral guest cations is however not observed.

A New Macrocycle Demonstrates Ditopic Recognition Properties.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New C2-symmetric 2,2′-bipyridine crown macrocycles for enantioselective recognition of amino acid derivatives

A series of new C 2-symmetric 2,2′-bipyridine-contaning crown macrocycles 1– 4 has been developed for enantiomeric recognition of amino acid derivatives. These new macrocycles have been showed to be strong complexing agents for primary organic ammonium salts (with K up to 4.83×10 5 M −1 and −Δ G 0 up to 32.4 kJ mol −1) and also useful chromophores for UV–vis titration studies. These macrocyclic hosts exhibited enantioselective binding towards the ( S)-enantiomer of phenylglycine methyl ester hydrochloride ( Am1 ) with K ( S) / K ( R) up to 2.10 (ΔΔ G 0=−1.84 kJ mol −1) in CH 2Cl 2 with 0.25% CH 3OH. The structure–binding relationship studies showed that the aromatic subunit and the ester group of the ammonium guests are both important for good enantioselectivity. In addition, the host–guest complexes have been studied using various NMR experiments.

Polarizing a Hydrophobic Cavity for the Efficient Binding of Organic Guests: The Case of Calix[6]tren, a Highly Efficient and Versatile Receptor for Neutral or Cationic Species

The host-guest properties of calix[6]tren 1 have been evaluated. The receptor is based on a calix[6]arene that is covalently capped at the narrow rim by a tren unit. As a result, the system presents a concave hydrophobic cavity with, at its bottom, a grid-like nitrogenous core. Despite its well-defined cavity and opening to the outside at the large rim, 1 did not behave as a good receptor for neutral molecules in chloroform. However, it exhibited efficient endo-complexation of ammonium guests. By contrast, the per-protonated host, 1.4H(+), behaved as a remarkable receptor for small organic molecules. The complexation is driven by a strong charge-dipole interaction and hydrogen bonds between the polar guest and the tetracationic cap of the calixarene. Finally, coordination of Zn(2+) to the tren core led to the asymmetrization of calixarene cavity and to the strong but selective endo-binding of neutral ligands. This study emphasizes the efficiency of a receptor presenting a concave hydrophobic cavity that is polarized at its bottom. The resulting combination of charge-dipole, hydrogen bonding, CH-pi, and van der Waals interactions highly stabilizes the supramolecular architectures. Also, importantly, the tren cap allows the tuning of the polarization, offering either a basic (1), a highly charged and acidic (1.4H(+)), or a coordination (1.Zn(2+)) site. As a result, the system proved to be highly versatile, tunable, and interconvertible in solution by simple addition of protons, bases, or metal ions.

Ab Initio Study of the Complexation Behavior of Calix[6](aza)cryptand with Alkyl Ammonium Cations

The structures and complexation energies of p-tert-butylcalix[6](aza)cryptand 1 with a series of alkylammonium cations have been calculated by using ab initio HF/6-31G method. After geometry optimizations, B3LYP/6-31G(d) single point calculations of the final structures are carried out including the effect of an electron correlation and the basis set with a polarization function. The calculated complexation efficiencies of 1 for alkylammonium guests are better than those of the previously reported calix[5]arenes, and much better than those of the calix[4]crown-6-ether. The calculation results show that calix[6](aza)cryptand also has much better complexation ability with smaller ammonium cations than with bulky alkylammonium guests. The structural characterizations of the calculated complexes are described as the function of the nature of the alkyl substituents of the ammonium guests.

A new macrocycle demonstrates ditopic recognition properties

The synthesis and binding properties of a new macrocycle is reported. The host, comprised of three basic pyridines, four hydrogen bond accepting carbonyls, and two hydrogen bond donating amide groups, binds mono-alkyl ammonium salts in a manner that is dependent on the counter-ion of the ammonium guest.

Chiral Discrimination on the Host–Guest Complexation of Resorc[4]arenes with Quarternary Amines

The interaction of inherently chiral resorc[4]arenes with different chiral ammonium ions was measured by ESI-MS. For that purpose one enantiomer of the ammonium guests was labeled with deuterium to distinguish the enantiomers by their mass. We synthesized the ammonium salts by reaction of chiral primary amines with either CH3I or CD3I and analyzed the resulting ammonium iodides by NMR and optical rotation. The complexation experiments were performed by mixing the chiral host with various ratios of the unlabeled guest and its labeled enantiomer. By analysis of the integrals of the host-guest complexes we observed a chiral discrimination effect and a secondary isotope effect as well.

A novel receptor based on a C3v-symmetrical PN3-calix[6]cryptand.

A C3v-symmetrical PN3-calix[6]cryptand was prepared in six steps from the known 1,3,5-tris-methylated calix[6]arene through a remarkably efficient [1 + 1] macrocyclization reaction. A 1H NMR study showed that the P,N-crypto cap rigidifies the whole edifice in a cone conformation ideal for molecular recognition applications. The ability of this new receptor to perform selective endo-complexation is illustrated with ammonium guests.

Ab Initio Study of the Complexation Behavior of p-tert-Butylcalix[5]arene Derivative toward Alkyl Ammonium Cations

The structures and complexation energies of penta-O-tert-butyl ester 1 of p-tert-butylcalix[5]arene toward a series of alkyl ammonium guests have been optimized by ab initio HF/6-31G method. The calculated complexation efficiencies of 1 for alkyl ammonium guests have been found to be similar to the values of previously reported debutylated-calix[5]arene 2. Calculation results show that both of the calix[5]aryl derivatives have much better complexation ability toward ammonium cation without alkyl group over other alkyl ammonium guests. The structural characteristics of the calculated complexes are discussed as a function of the nature of the alkyl substituents of the ammonium guests.

Threshold dissociation energies of protonated amine/polyether complexes in a quadrupole ion trap

Electrospray ionization mass spectrometry (ESI-MS) is increasingly used to probe the nature of noncovalent complexes; however, assessing the relevance of gas-phase results to structures of complexes in solution requires knowledge of the types of interactions that are maintained in a solventless environment and how these might compare to key interactions in solution. This study addresses the factors impacting the strength of hydrogen bonding noncovalent interactions in the gas phase. Hydrogen bonded complexes consisting of ammonium ions bound to polydentate ethers are transported to the gas phase with ESI, and energy-variable collisional activated dissociation (CAD) is used to map the relative dissociation energies. The measured relative dissociation energies are correlated with the gas-phase basicities and steric factors of the amine and polyether constituents. To develop correlations between hydrogen bonding strength and structural features of the donor and acceptor molecules, a variety of amines with different gas-phase basicities and structures were selected, including primary, secondary, and tertiary amines, as well as those that are bidentate to promote intramolecular hydrogen bonding. The acceptor molecules are polydentate ethers, such as 18-crown-6. Four primary factors influence the observed dissociation energies of the polyether/ammonium ion complexes: the gas-phase basicities of the polyether and amine, steric effects of the amines, conformational flexibility of the polyethers, and the inhibition of intramolecular hydrogen bonds of the guest ammonium ions in the resulting ammonium/polyether noncovalent complexes.

Ab Initio Study of the Complexation Behavior of Calix[5]arene Derivative toward Alkyl Ammonium Cations

The structures and complexation energies of penta-O-alkylated 1b and penta-O-tert-butyl ester 1e of p-tert-butylcalix[5]arene and their simplified structures (2b and 2e) toward a series of alkyl ammonium guests have been calculated by a semi-empirical AM1 method. For AM1 calculations, complexation efficiencies of the simplified host 2e are very similar to the values of host 1e. The complexes of simplified host 2e with alkyl ammonium ions also have been optimized by ab initio HF/6-31G method. The calculated complexation efficiencies for 2e by ab initio method have been found to be bigger in magnitude than the values obtained by AM1 calculations for linear alkyl ammonium guests. Calculation results show that all of the calix[5]aryl derivatives investigated in this study have much better complexation ability toward ammonium cation without alkyl group compared with other alkyl ammonium guests. Ab initio calculations also well duplicate the molecular discriminating behaviors of calix[5]arene derivative 2e between butyl ammonium ions: <TEX>$n-BuNH_3^+\;>\;iso-BuNH_3^+\;>\;sec-BuNH_3^+\;>\;tert-BuNH_3^+$</TEX>.

Kinetic and thermodynamic consequences of the substitution of SMe for OMe substituents of cryptophane hosts on the binding of neutral and cationic guests.

To investigate the origin of the high selectivity of cryptophane-E (1) towards Me3NH+, Me4N+, and CHCl3, and particularly to discriminate the different contributions that stabilize the supramolecular complexes, we have synthesized the new cryptophane 2 bearing six MeS groups instead of MeO groups in 1. This led to a decrease of the negative charge density in the equatorial region of 2 without affecting notably the size of the molecular cavity. The binding properties of 1 and 2 towards the three guests were examined in solution and showed a slight decrease of the deltaGa favoring the complexes of 1, accompanied by a significant modification of the deltaHa vs. deltaSa balance. The binding of the ammonium guests to 1 and 2 was strongly entropy driven, while that of CHCl3 was purely enthalpy driven. A combination of spectroscopic and computational techniques was used to assign the main intermolecular interactions that occurred during the inclusion process. The neutral CHCl3 molecule is more stabilized in the less negatively charged CTV cap of 1. The different behavior towards the ammonium cations can be explained in term of interactions with the electronegative heteroatoms and cation-pi interactions. Moreover, this study revealed a considerable slowing down of the guest exchange kinetics with host 2, for which the association and dissociation rates are reduced by a factor 10(3) to 10(4) with respect to 1. For example, at room temperature, the Me4N+@2 complex exhibits a half-life of ca. 2 years, instead of a few hours for the corresponding complex of 1.

Role of pyridine hydrogen-bonding sites in recognition of basic amino acid side chains.

A series of three, new artificial receptors for guanidinium and ammonium guests has been synthesized. All three receptors have highly preorganized clefts bearing two carboxylate groups. They differ in the number of nitrogen atoms contained in their clefts, as follows: four N atoms in receptor 3, three N atoms in 4, and two nitrogens in 5. Crystallographic studies have produced the solid-state structures of the following guanidinium complexes of each receptor: 3.2CH(3)CH(2)NHC(NH(2))(2)(+), 4.2CH(3)NHC(NH(2))(2)(+), and 5.2C(NH(2))(3)(+). The conformations of the receptor molecules in all three complexes are very similar. N-Alkylguanidinium guests are bound in the clefts of 3 and 4 in similar manners, despite the loss of one hydrogen-bond acceptor nitrogen in 4 and the possible hindrance of the cavity by a CH group. In the guanidinium complex of 5, neither guest enters the cavity containing two CH groups. Complexation studies were conducted in methanol by (1)H NMR titration for several guanidinium and ammonium guests, including derivatives of the amino acids arginine and lysine. Receptor 5 binds all such guests weakly (K(s) < 4000), while 3 binds most guests very strongly (K(s) > 100 000). Receptor 3 is selective for arginine versus lysine, while 4 binds lysine better than does 3. The results generally underscore the importance of receptor preorganization and hydrogen-bonding complementarity in the design of receptors that can serve as probes for biomolecules.