Resorcinarene Host Research Articles

Ab initio design of drug carriers for zoledronate guest molecule using phosphonated and sulfonated calix[4]arene and calix[4]resorcinarene host molecules

Monomolecular drug carriers based on calix[n]-arenes and -resorcinarenes containing the interior cavity can enhance the affinity and specificity of the osteoporosis inhibitor drug zoledronate (ZOD). In this work we investigate the suitability of nine different calix[4]-arenes and -resorcinarenes based macrocycles as hosts for the ZOD guest molecule by conducting {\it ab initio} density functional theory calculations for structures and energetics of eighteen different host-guest complexes. For the optimized molecular structures of the free, phosphonated, sulfonated calix[4]-arenes and -resorcinarenes, the geometric sizes of their interior cavities are measured and compared with those of the host-guest complexes in order to check the appropriateness for host-guest complex formation. Our calculations of binding energies indicate that in gaseous states some of the complexes might be unstable but in aqueous states almost all of the complexes can be formed spontaneously. Of the two different docking ways, the insertion of ZOD with the \ce{P-C-P} branch into the cavity of host is easier than that with the nitrogen containing heterocycle of ZOD. The work will open a way for developing effective drug delivering systems for the ZOD drug and promote experimentalists to synthesize them.

Chirality Induction from a Chiral Guest to the Hydrogen-Bonding Network of Its Hexameric Resorcinarene Host Capsule.

The hexameric capsule of resorcin[4]arene 1 is capable of encapsulating tertiary amines, which has recently been used in the application of [(1)6 (H2 O)8 ] as (co-)catalyst in various asymmetric reactions. However, not much is known about the highly asymmetric but conformationally very dynamic structure of the capsule after uptake of chiral molecules. Therefore, in this contribution, we utilize electronic circular dichroism and vibrational circular dichroism spectroscopy to investigate how several chiral guest molecules affect the structural preferences of the capsule [(1)6 (H2 O)8 ]. In particular, we show that one small chiral amine encapsulated in [(1)6 (H2 O)8 ] is sufficient to control and dictate the stereochemical preferences of the entire capsule. Furthermore, neither strong π-π interactions nor a significant steric bulk are required for this induction. The observation of such a chiral imprint of the guest's stereochemistry onto its host molecule is expected to have implications also for other supramolecular capsules.

Ionic Imprinting Polymers Using Diallylaminomethyl-Calix[4] Resorcinarene Host for the Recognition of Pb (II) Ions

A novel ion-imprinted microspheres of copolymerized diallylaminomethyl-calix [4] resorcinarene and divinylbenzene were prepared through precipitation polymerization. These microspheres were used for the adsorption experiments of Pb (II) ions mixture solution containing Pb (II), Ni (II) and Cu (II). The selective complexion towards Pb (II) ions was examined. The adsorption was conducted in batches by investigating the effects of pH and initial concentration of a heavy metal solution. The adsorption of Pb (II) metal ions on the adsorbents had the optimum pH rating in region of 6. For single ion system, the imprinted polymer showed that the adsorption capacity of Pb (II) metal ions was 64 mg/g, while for Cu (II and Ni (II) were 24 mg/g and 8 mg/g, respectively. Competitive extraction experiments in the presence of Cu (II) and Ni (II) ions were also carried out and high selectivity of the imprinted polymer adsorbents towards Pb (II) over Cu (II) and Ni (II) was found. In ternary mixture of heavy metal ions, the imprinted polymer showed effective adsorption to Pb (II) obeying Langmuir isotherm. The outstanding adsorption abilities for Pb (II) metal ion have exhibited good prospects for disposal application of polluted water and environmental protection.

Ionic Imprinted Calix[4]resorcinarene Host for Pb(II) Adsorbent Using Diallylaminomethyl–Calix[4]resorcinarene Copolymer

Abstract Novel imprinted calix[4]resorcinarene host diallylaminomethyl–calix[4]resorcinarene was developed and copolymerized with divinylbenzene for selective extraction of Pb(II). In ternary mixture of heavy metal ions, the imprinted polymer showed effective adsorption to Pb(II) obeying the Langmuir isotherm.

Solvent driven formation of silver embedded resorcinarene nanorods

Silver complexes of resorcinarene bis-crown-5 were observed to arrange into nanorods of 2.4 nm in diameter. The left- and right-handed isomers of the inherently chiral resorcinarene host are separated into their own entity in the self-assembly process with the periphery of the nanorods consisting of silver cations included in the cavity.

Resorcinarene-based cavitands with chiral amino acid substituents for chiral amine recognition

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (AMA), alanine undecyl resorcinarene acid (AUA) and glycine undecyl resorcinarene acid (GUA), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of AMA, AUA, and GUA with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary L-tartaric acid and the monoacid phthalyl alanine (PA). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary L-tartaric acid only binds one amine guest strongly. The simple compound PA, which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of AUA with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.

Resorcinarene Podand with Amine‐Functionalized Side Arms – Synthesis, Structure, and Binding Properties of a Neutral Anion Receptor

AbstractThe synthesis and structure of a neutral resorcinarene host bearing four amine‐functionalized side arms is described. The anion binding properties were investigated in solution by 1H NMR spectroscopic titration and diffusion experiments and in the gas phase by mass spectrometric studies. It was observed that in solution 1:2 (host/guest) complexes were formed between the resorcinarene host and the basic fluoride and acetate anions, whereas in the gas phase 1:1 complexes with other anions (Cl–, HCOO–, NO3–, and BF4–) were detected additionally. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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.

Formation of ionic associates from oppositely charged calix[4]resorcinarene host molecules in the presence of guest molecules

The conditions for the formation and existence of capsular dimeric associates in a solution were studied. The associates are formed by the oppositely charged resorcinarene derivatives (tetrakis(dimethylaminomethyl)calix[4]resorcinarene hydrochloride and tetrakis(sulfonato- methyl)calix[4]resorcinarene). Possibilities of formation of a capsule in the presence of the molecules giving inclusion complexes with one of the macrocycles were considered. Switching between two states “capsular associate—mixture of original macrocycless” is achieved by controlling the ionic strength of the solution. The interaction of the host—guest complexes with complementary resorcinarene leads to capsular associate closure with the synchronous displacement of the guest molecules into the aqueous solution bulk.

The role of cation⋯π interactions in capsule formation: co-crystals of resorcinarenes and alkyl ammonium salts

An unprecented dimeric capsular assembly of a tetramethylated C-hexyl resorcinarene and an expected one from unsubstituted C-butyl resorcinarene with tetramethylammonium cation are described. Surprisingly tetramethylated C-hexyl resorcinarene, with no apparent possibility for intra-capsular hydrogen bonds, forms a capsule which is held together solely by the cation⋯π interactions and the complementary geometry of the spherical guest cation and the concave resorcinarene host. The C-butyl resorcinarene capsule, as in the case of dimeric resorcinarene capsules reported earlier, is mediated viasolvent molecules and intra-capsular hydrogen bonds. We also report here two co-crystals of C-methyl resorcinarene and one of C-(3-hydroxy)propyl resorcinarene with R2,R′2-type of alkyl ammonium halide salts. These structures manifest the difficulty of structure control and prediction due to competing and multiple interactions in the crystalline state. The design of the resorcinarene-based host–guest system so as to enable prediction or inducement of a specific crystal packing or structural arrangement of host and guest, is very difficult, if not impossible due to the cameleon nature of resorcinarenes in their ability to form weak interactions.

Flattened Cone 2,8,14,20‐Tetrakis(L‐valinamido)[4]resorcinarene: An Enantioselective Allosteric Receptor in the Gas Phase

A get-out clause: Displacement of the enantiomers of tryptophan from the achiral hydrophobic rim of a flattened cone resorcinarene derivative is induced by 2-aminobutane (B). The displacement exhibits a marked enantioselectivity which is traced to a conformational coupling between the achiral hydrophobic rim of the resorcinarene host and its chiral hydrophilic rim wherein the 2-aminobutane enantiomers are trapped.

Selective enclathration of picoline isomers by a resorcinarene host

The resorcinarene host 14,16,54,56-tetrahydroxy-2,4,6,8-tetrapentyl-34,36,74,76-tetra(p-toluene-sulfonyl-oxy)-1,3,5,7(1,3)-tetrabenzenacyclooctaphane forms inclusion compounds with 2-, 3- and 4-picoline. The structures of these inclusion complexes have been elucidated and compared, with some being found to additionally include water molecules as guests. Competition experiments were carried out to determine whether this host would selectively enclathrate any of the picolines and thus investigate the capability of this host for the separation of picoline isomers. A very interesting result was obtained for the 3-picoline versus 4-picoline competition experiment, which displays a concentration dependent selectivity, but instead of selective inclusion of the guest of higher concentration, it was in fact the guest of lower concentration in the solution which was preferentially enclathrated. This unusual result was explained in terms of solubilities of the clathrates in the two guests.

Selectivity of a Resorcinarene Host for Pentanol Isomers

The resorcinarene host H=14,16,54,56-tetrahydroxy-2,4,6,8-tetrapentyl-34,36,74,76-tetra(p-toluenesulfonyloxy)-1,3,5,7(1,3)-tetrabenzenacyclooctaphane was found to form inclusion compounds with seven pentanol isomers, namely 1-pentanol (H·2(1PENT)), 2-pentanol (H·2(2PENT)), 3-pentanol (H·2(3PENT)), 2-methyl-1-butanol (H·2(2M1B)), 3-methyl-1-butanol (H·2(3M1B)), 2-methyl-2-butanol (H·2(2M2B)) and 3-methyl-2-butanol (H·2(3M2B)). These compounds were characterized by thermal analysis, which showed that they all have host-guest (H:G) ratios of 1:2, and their structures were elucidated and compared. Competition experiments were carried out to investigate the selectivity of this host for some of the pentanol guests and thereby investigate the capability of this host for the separation of pentanol isomers.

Ionic interactions and multilayer structures on self-assembled surfaces of calix[4]resorcinarene

The ionization of a self-assembled monolayer of tetrathiol calix[4]resorcinarene, which is a synthetic host in guest–host recognition phenomena, was investigated. Using surface plasmon resonance measurements, it was found that ionization of the self-assembled surface occurred in water at a pH of approximately 11.5. These ionized surfaces of calix[4]resorcinarene were used to bind ionic guests such as metallic copper ions that were further exploited in the formation of supramolecular ionic assemblies of calix[4]resorcinarene. The structure of the molecular assemblies was characterized using polarization modulation infrared reflection absorption spectroscopy. The use of ionic interactions to attach molecules such as 11-mercapotundecanoic acid to the upper rim of the calix[4]resorcinarene host was also investigated as a method for simple and non-covalent modification of the host cavity.

Ionic interactions and multilayer structures on self-assembled surfaces of calix[4]resorcinarene

The ionization of a self-assembled monolayer of tetrathiol calix[4]resorcinarene, which is a synthetic host in guest–host recognition phenomena, was investigated. Using surface plasmon resonance measurements, it was found that ionization of the self-assembled surface occurred in water at a pH of approximately 11.5. These ionized surfaces of calix[4]resorcinarene were used to bind ionic guests such as metallic copper ions that were further exploited in the formation of supramolecular ionic assemblies of calix[4]resorcinarene. The structure of the molecular assemblies was characterized using polarization modulation infrared reflection absorption spectroscopy. The use of ionic interactions to attach molecules such as 11-mercapotundecanoic acid to the upper rim of the calix[4]resorcinarene host was also investigated as a method for simple and non-covalent modification of the host cavity.

Thiophosphorylated cavitand: structure and affinity towards soft metal ions

The iiii stereoisomer of the tetrathiophosphonate-calix[4]resorcinarene host 1 exhibited excellent extraction properties towards soft metal ions, with a better affinity for Ag + (91%), than for Tl + (38%) and Hg 2+ (16%). The extraction of other picrate salts (Cu 2+, Ni 2+, Co 2+, Zn 2+, Cd 2+, Pb 2+) was not detected. The stoichiometry and the structure of the Hg 2+, Tl + and Ag + complexes were studied by NMR in solution and gave respectively 1:1, 1:1 and 1:2 host–guest complexes. The formation of the self-assembled 1 2·(AgPic) 4 complex was independent on the anion and only observed with silver(I) ion.

Study of the Complexation of Octakis(diethoxyphosphoryloxy)-tetramethylcalix[4]resorcinarene with Benzene Derivatives by the RP HPLC Method

Stability constants of the host–guest complexes of octakis(diethoxyphosphoryloxy) tetramethylcalix[4]resorcinarene (RA) with different benzene derivatives (alkyl benzenes, halogenated benzenes, substituted aldehydes, phenols and benzoic acids) were determined by the reversed phase high-performance liquid chromatography (RP HPLC) method (Separon SGX C 18, UV detector at 254 nm and acetonitrile-water, 86 : 14, v/v, as mobile phase) from the relationship between the aromatic guest capacity factors and the RA host concentration in the mobile phase. The constants are within the range 17–596 M−1, dependent on the size, nature, position and quantity of the substituents in the benzene ring of the guest molecules.