Host-guest Adducts Research Articles

Visible light-driven water oxidation promoted by host-guest interaction between photosensitizer and catalyst with a high quantum efficiency.

A highly active supramolecular system for visible light-driven water oxidation was developed with cyclodextrin-modified ruthenium complex as the photosensitizer, phenyl-modified ruthenium complexes as the catalysts, and sodium persulfate as the sacrificial electron acceptor. The catalysts were found to form 1:1 host-guest adducts with the photosensitizer. Stopped-flow measurement revealed the host-guest interaction is essential to facilitate the electron transfer from catalyst to sensitizer. As a result, a remarkable quantum efficiency of 84% was determined under visible light irradiation in neutral aqueous phosphate buffer. This value is nearly 1 order of magnitude higher than that of noninteraction system, indicating that the noncovalent incorporation of sensitizer and catalyst is an appealing approach for efficient conversion of solar energy into fuels.

Computational Study on the Mechanism of the Acceleration of 1,3-Dipolar Cycloaddition inside Cucurbit[6]uril

The enhanced reactivity of the Huisgen 1,3-dipolar cycloaddition between the protonated forms of azidoethylamine and propargylamine inside the cucurbit[6]uril host has been computationally studied. A DFT approach is applied to explore the relative stabilities and connections of a large variety of possible host–guest aggregates that may be formed in solution, as well as their reactivity. The free energies resulting from the DFT calculations are converted to rate and dissociation constants and introduced, together with the experimentally reported initial concentrations, in a kinetic simulation. The results reproduce the experimental observations and provide a detailed description of the behavior of a large host–guest system over time. The major cause of the rate acceleration inside the nanovessel is the reduction of the entropic component of the free energy barrier, and the existence of stable nonproductive host–guest adducts is identified as a major obstacle to improved catalysis.

Sponge-like molecular cage for purification of fullerenes.

Since fullerenes are available in macroscopic quantities from fullerene soot, large efforts have been geared toward designing efficient strategies to obtain highly pure fullerenes, which can be subsequently applied in multiple research fields. Here we present a supramolecular nanocage synthesized by metal-directed self-assembly, which encapsulates fullerenes of different sizes. Direct experimental evidence is provided for the 1:1 encapsulation of C60, C70, C76, C78 and C84, and solid state structures for the host-guest adducts with C60 and C70 have been obtained using X-ray synchrotron radiation. Furthermore, we design a washing-based strategy to exclusively extract pure C60 from a solid sample of cage charged with a mixture of fullerenes. These results showcase an attractive methodology to selectively extract C60 from fullerene mixtures, providing a platform to design tuned cages for selective extraction of higher fullerenes. The solid-phase fullerene encapsulation and liberation represent a twist in host-guest chemistry for molecular nanocage structures.

Chiral Recognition and Partial Resolution of 1-Phenylethylamine through Noncovalent Interactions Using Binuclear Ni(II) Complex as Host

Chiral recognition through noncovalent interaction occurs in many biological systems. Structural characterization of chiral host–guest complexes can enhance the understanding of recognition mechanism. but such examples are relatively few. Chiral recognition and resolution of 1-phenylethylamine was studied where a binuclear Ni(II) complex acts as chiral host. Structural characterization showed that (R)-1-phenylethylamine forms a triangular assembly of three host–guests adducts through both H-bond and CH···π interactions. In contrast, use of (S)-1-phenylethylamine leads to formation of ∼11 Å wide one-dimensional channels by the binuclear Ni(II) anionic complex where the chiral guest cation has been organized inside the channels in a zigzag fashion. Use of racemic amine yielded crystals having identical channel structure where S-amine and R-amine are inside the channels in a 55:45 ratio. HPLC results of the isolated amines from bulk of the crystals show that the S:R isomer ratio is 65:35, supporting the structural observation. HPLC on the isolated amine from amorphous precipitate of host–guest adduct showed minor (4% ee) chiral enhancement, indicating that this enhancement is mostly due to noncovalent interactions in the crystalline state. Resolution of enantiomers through crystallization is a result of solution thermodynamics, nucleation, and other factors pertaining to the crystalline state. Results presented attempted to show the extent of this interdependence within a chiral metallo-organic host and an amine.

Dendrimeric β-cyclodextrin/Gd(III) chelate supramolecular host-guest adducts as high-relaxivity MRI probes.

We have synthesized a new macromolecular architecture, (PAMAM)-CD8 , which consists of eight β-cyclodextrin units (β-CD) attached to a generation 1 poly(amidoamine) (PAMAM) dendrimer through a disulfide bond, which can be cleaved under reducing conditions. This system shows a pronounced hosting capability towards Gd(III) chelates functionalized with hydrophobic groups, thus leading to well-defined supramolecular adducts. (1)H NMR relaxometric investigations were carried out to follow the formation of adducts with three Gd(III) chelates based on the ligand architectures of 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid (AAZTA) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suitably functionalized with benzyl or adamantyl (Ad) pendant groups. In particular, the ditopic complex composed of two AAZTA chelating units connected to a central aromatic ring that bears an adamantyl group showed a strong affinity (ca. 10(6) M(-1)) for the CD units of the dendrimer, which is two orders of magnitude higher than toward human serum albumin (HSA). Remarkable relaxivity enhancements (i.e., up to 71% at 1 T and 25 °C) were observed upon the formation of the macromolecular host-guest adducts due to a decrease in the molecular tumbling rate and fast water-exchange. Reduction experiments and competition studies between the paramagnetic dendrimer and HSA were carried out by relaxometric techniques. The results show that the metal complexes are not displaced by the protein, thus suggesting that this novel macromolecular probe is potentially suitable for applications in vivo.

A new ditopic GdIII complex functionalized with an adamantyl moiety as a versatile building block for the preparation of supramolecular assemblies

A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) bearing an adamantyl group (Gd2L1) able to form strong supramolecular adducts with specific hosts such as β-cyclodextrin (β-CD), poly-β-CD, and human serum albumin (HSA) is reported. The relaxometric properties of Gd2L1 were investigated in aqueous solution by measuring the (1)H relaxivity as a function of pH, temperature, and magnetic field strength. The relaxivity of Gd2L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM(-1) s(-1), a value that remains almost constant at higher fields owing to the great compactness and rigidity of the bimetallic chelate, resulting in an ideal value for the rotational correlation time for high-field MRI applications (1.5-3.0 T). The noncovalent interaction of Gd2L1 with β-CD, poly-β-CD, and HSA and the relaxometric properties of the resulting host-guest adducts were investigated using (1)H relaxometric methods. Relaxivity enhancements of 29 and 108 % were found for Gd2L1-β-CD and Gd2L1-poly-β-CD, respectively. Binding of Gd2L1 to HSA (KA = 1.2 × 10(4) M(-1)) results in a remarkable relaxivity of 41.4 mM(-1) s(-1) for the bound form (+248 %). The relaxivity is only limited by the local rotation of the complex within the binding site, which decreases on passing from Gd2L1-β-CD to Gd2L1-HSA. Finally, the applicability of Gd2L1 as tumor-targeting agent through passive accumulation of the HSA-bound adduct was evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor-bearing mice. These experiments indicate a considerable signal enhancement (+160 %) in tumor after 60 min from the injection and a very low hepatic accumulation.

Supramolecular β-Cyclodextrin Adducts of Boron-Rich DNA Metallointercalators Containing Dicarba-closo-dodecaborane(12)

A chiral, isomeric series of novel boron-rich Pt(II) metallointercalators ([PtL2(phen)](NO3)2: L = (x)-(1,y-closo-carboran-1-yl)pyrid-z-ylmethanol: x = R, S; y = 7, 12; z = 3, 4) wre prepared and fully characterized. By means of variable-temperature NMR spectroscopy, different combinations of Δ-head-to-tail, head-to-head, and Λ-head-to-tail rotamers were identified, and the free energies of activation for Pt-N bond rotation were determined for the pyrid-4-yl complexes with ΔG(‡)307 = 16.1 ± 0.3 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,7-carboranyl derivative and ΔG(‡)307 = 16.4 ± 0.5 kcal mol(-1) and ΔG(‡)325 = 16.2 ± 0.5 kcal mol(-1) for the 1,12-carboranyl derivative. The corresponding 2:1 host-guest β-cyclodextrin (β-CD) adducts ([PtL2(phen)·2β-CD](NO3)2) were also prepared and fully characterized by high resolution electrospray ionization mass spectrometry and 2D-(1)H{(11)B} nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy NMR experiments. The interaction of the novel supramolecular adducts with calf thymus DNA was investigated by means of linear dichroism, ultraviolet-visible spectroscopy, thermal denaturation, and isothermal titration calorimetry experiments which revealed a bimodal binding regime with DNA intercalation favored at low [drug]/[DNA] ratios, while at higher drug loading, surface aggregation was observed. Furthermore, the data were also consistent with some degree of dissociation of the β-CD host-guest adducts upon DNA binding. When we used a single binding-site model, interpreted as a weighted average of all of the possible equilibrium interactions, the compounds showed high affinity for ct-DNA with K(assoc) ranging from (1.3 ± 0.1) × 10(5) M(-1) to (5.7 ± 0.4) × 10(5) M(-1). In general, the overall DNA-binding behavior was enthalpically driven with a minor or unfavorable entropic component, which is consistent with the thermodynamics of an intercalation-dominated process. A higher degree of DNA intercalation was observed for the R-isomer in the pyrid-3-yl compounds, and the opposite trend was observed in the case of pyrid-4-yl derivatives.

Guest Covalent Capture by a Host: A Biomimetic Strategy for the Selective Functionalization of a Cavity

A biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host-guest chemistry (mimicking the Michaelis-Menten adduct in enzymes) and allows the finely tuned pre-organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process. The scope of the reaction was explored and the results suggest that such a supramolecular strategy is quite versatile and could be applied to the selective functionalization of other cavitands bearing different recognition patterns. A detailed structural, thermodynamic, and kinetic study is also reported, highlighting interesting biomimetic features: The importance of the host-guest adduct strength, the high sensitivity of the reaction to the pre-organization of the reactive partners (alkyne vs. azide), and a significant impact of the embedment on the transition state. The self-coordination of the monofunctionalized products was also studied and an "endo/exo" switch of the internal side-chain could be triggered by adding competitive ligands.

Synthesis and Supramolecular Studies of Chiral Boronated Platinum(II) Complexes: Insights into the Molecular Recognition of Carboranes by β‐Cyclodextrin

The synthesis and characterisation of a novel isomeric family of closo-carborane-containing Pt(II) complexes ((R/S)-(1-4)⋅2 NO(3)) are reported. Related complexes (5⋅NO(3) and 6⋅NO(3)) that contain the 7,8-nido-carborane cluster were obtained from the selective deboronation of the 1,2-closo-carborane analogues. The corresponding water-soluble supramolecular 1:1 host-guest β-cyclodextrin (β-CD) adducts ((R/S)-(1-4)⋅β-CD⋅2 NO(3)) were also prepared and fully characterised. HR-ESI-MS experiments confirmed the presence of the host-guest adducts, and 2D-(1) H{(11)B} ROESY NMR studies showed that the boron clusters enter the β-CD from the side of the wider annulus. Isothermal titration calorimetry (ITC) experiments revealed enthalpically driven 1:1 and higher-order supramolecular interactions between β-CD and (R/S)-(1-4)⋅2 NO(3) in aqueous solution. A comparison of the predominate 1:1 binding mode established that the affinity of β-CD for the guest molecule is mainly influenced by the pyridyl ring substitution pattern and chirality of the host, whilst the nature of the closo-carborane isomer also plays some role, with the most favourable structural features for β-CD binding being the presence of the 4-pyridyl ring, 1,12-closo-carborane, and an S configuration. The results reported here represent the first comprehensive calorimetric study of the supramolecular interactions between closo-carborane compounds and β-CD, and it provides fascinating insights into the structural features influencing the thermodynamics of this phenomenon.

Stimuli-responsive Pd2L4metallosupramolecular cages: towards targeted cisplatin drug delivery

Metallosupramolecular cages are an emerging, but as of yet relativity unexplored, drug delivery vector. Herein we show that discrete dipalladium(II) molecular cages of the formula [Pd2L4](X)4 can be quantatively self-assembled from a simple tripyridyl ligand (2,6-bis(pyridin-3-ylethynyl)pyridine) and [Pd(CH3CN)4](X)2 (X = BF4− or SbF6−). The cages have been fully characterised using 1H, 13C and DOSY NMR spectroscopy, elemental analysis, IR spectroscopy, and high resolution electrospray mass spectrometry (HR-ESMS). Additionally, the molecular structure of the [Pd2L4](SbF6)4 cage was confirmed unequivocally using X-ray diffraction. These [Pd2L4](X)4 cages are stimuli-responsive and can be reversibly disassembled/reassembled upon the addition/removal of suitable competing ligands. The central cavities of the [Pd2L4](X)4 cages are lined with four hydrogen bond accepting pyridine units which enable the encapsulation of two cisplatin molecules within the metallosupramolecular architecture through hydrogen bonding interactions between the cage and the amine ligands of the cisplatin guest. The structure of the [Pd2L4⊃(cisplatin)2](BF4)4 host–guest adduct has been confirmed by 1H NMR spectroscopy, HR-ESMS and X-ray crystallography. Additionally we have demonstrated that the cage–cisplatin host–guest adduct can be quantatively disassembled upon the addition of a competing ligand, releasing the cisplatin guest. This is the first crystallographically characterised example of a discrete metallosupramolecular cage encapsulating an FDA-approved inorganic drug molecule. This host–guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics.

Ammonium–crown ether based host–guest systems: N–H⋯O hydrogen bond directed guest inclusion featuring N–H donor functionalities in angular geometry

This article demonstrates crown ether based host–guest adduct formation in a series of crystalline solids 1–7, in which ammonium-type cationic guests have been integrated with various crown ethers. Addition of more than two equivalents of perchloric acid to an acetonitrile solution of 3-aminopyridine (3AmPy), 4,4′-diaminodiphenylmethane (DADPM) or 4,4′-diaminodiphenylether (DADPE) generates the doubly protonated anilinium (or ammonium) cationic species (written as 3AmPyH2, DADPMH2 and DADPEH2 respectively) which act as guests to the various crown ether hosts present in solution. The relevant compounds crystallize as their perchlorate salts and they have been structurally characterized through X-ray diffraction. The major driving force towards host–guest complexation in the compounds 1–7 is found to be the N–H⋯O hydrogen-bond interactions between the aforementioned guests and the crown ether hosts.

Recognition of primary amines in water by a zinc funnel complex based on calix[6]arene

A water-soluble calix[6]arene-based tris(imidazole) ligand behaves as a highly selective receptor for primary amines in the presence of Zn(II) in water near physiological pH. It represents the first compound of this family of ligands that binds a Zn dication and an organic guest in water, thus giving rise to a stable host–guest adduct in spite of the highly competitive medium. The herein described self-assembly process displays a remarkable set of biomimetic properties. The ternary system (calix/Zn/amine) is formed in a very synergistic and allosteric manner and stabilizes the neutral form of the amino guest with a spectacular pseudo-pKa shift of ca. 7 units. This system constitutes an interesting structural model of metalloenzymes in aqueous solution.

Selective Binding of Glyphosate by a Ditopic Cyclic–Open‐Chain Polyazaligand in Aqueous Solution

AbstractThis paper reports a study of the interaction between a ditopic cyclic–open‐chain polyazaligand L1py and the herbicide glyphosate [N‐(phosphonomethyl)glycine or PMG] by potentiometric titrations as well as calorimetry and NMR measurements. This nonsymmetrical ligand is composed of a cyclam unit (1,4,8,11‐tetraazacyclotetradecane) and the linear tetraamine 1,4,8,11‐tetraazaundecane linked by a 2,6‐dimethylpyridine spacer. This ligand forms stable adducts with PMG. For comparison, two analogous symmetrical ditopic ligands, a bis‐macrocycle L4py and a bis‐tetraamine L5py, and two related anions, iminodiacetic acid (IDA) and iminobis(methylphosphonic acid) (IDP), were also investigated. The results unambiguously show that L1py selectively binds PMG, especially around neutral pH, whereas L4py and L5py exhibit a weaker affinity for this substrate. Calorimetic and 1H NMR measurements showed that the host–guest adducts are mainly stabilized by charge–charge interactions and hydrogen bonds involving the ammonium function of PMG and the nonprotonated nitrogen atom of the pyridine linker.

Thermally induced reversible conformational changes in the host–guest adduct of meso-tetramethyltetrakis(ethyl)calix[4]pyrrole

The binding of methanol, ethanol, and N, N-dimethylformamide to meso-tetramethyltetrakis(ethyl)calix[4]pyrrole ( 1) was investigated in both solid and solution with the exhibition of multi-fashion hydrogen bonding as shown by X-ray crystallography. The thermodynamic stability of these host–guest inclusion complexes were determined by exploiting TGA and DTA. An unexpected conformational change in 1·2EtOH occurred by thermal induction.

Hydration and flexibility of α-, β-, γ- and δ-cyclodextrin: A molecular dynamics study

The conformational behaviour in vacuo and in explicit water, and the hydration of the macrocyclic oligosaccharides cyclodextrins (CDs) containing from six up to nine sugar rings have been studied by atomistic molecular dynamics simulations. CDs are relatively soluble in water, but show a hydrophobic cavity wherein they may host appropriate guests, thus acting as a carrier of lipophilic molecules in an aqueous environment. In this paper, we discuss the size and conformation of cyclodextrins, including in particular their flexibility in solution, and their hydration pattern through the description of clusters of water molecules included within the cavity, as observed experimentally in the crystalline state. The resulting picture allows a better understanding of the efficiency of these molecules to form host–guest adducts.

Formation and X-ray structure of the host–guest adduct [Pd3(dppm)3(CO)(NO3)]+ and the mechanism of its electrochemical reduction

[Pd3(dppm)3(CO)]2+, [Pd3]2+, reacts with NO3– to form the host–guest adduct [Pd3(dppm)3(CO)(NO3)]+, [Pd3(NO3)]+. The presence of NO3– inside the cavity is confirmed by X-ray crystallography. Using a qualitative relationship between λmax (UV–vis) and the association constant of various adducts, the relative binding between NO3– and [Pd3]2+ is in the same order of magnitude of that between CF3CO2– and [Pd3]2+. Based on Pd···O distances, the NO3– ion is relativity more weakly associated to [Pd3]2+ in comparison with the known [Pd3(CF3CO2)]+. Using variation of [NO3–] in the presence of [Pd3](PF6)2 and variation of scan rates, the resulting cyclic voltammogramms (CV) were simulated to extract both kinetic and thermodynamic constants associated to a square scheme. Both the anodic and cathodic scans of the title cluster exhibits ECE mechanisms (E = electrochemical process; C = chemical process). For the anodic scan, the EEC event is not ruled out, at least as a minor process.Key words: nitrate, palladium cluster, adduct, electrochemistry, X-ray structure, rate constant, equilibrium constant.

Fluorescence modulation in anion sensing by introducing intramolecular H-bonding interactions in host–guest adducts

Fluorescence signaling in anion binding is modulated from quenching to enhancement by intramolecular H-bonding stabilization of anion-ionophore adducts; the intramolecular H-bonding is suggested to suppress the quenching processes otherwise possible and increase the conformational rigidity of the anionic adducts, leading to fluorescence enhancement in a selective fashion towards cyanide ion, among the various anions examined.

Molecular Recognition – Allosterism Generated by Weak Host–Guest Interactions in Molecular Rectangles

AbstractTwo metal‐based molecular rectangles that bear two identical binding sites form 1:2 host–guest adducts with a pair of analogous planar Pt2+ complexes. The larger of the two guests shows no binding allosterism with either of the two rectangles, but substantial positive allosterism is observed when the smaller guest binds to the rectangles. It is proposed that the smaller guest is better accommodated in the binding sites of the receptor and that this leads to allosterism. Various experiments, including 1H NOESY spectroscopy, support the supposition that the smaller guest is better incarcerated in the receptors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Molecular Recognition: Use of Metal‐Containing Molecular Clefts for Supramolecular Self‐Assembly and Host–Guest Formation

AbstractMolecular clefts consisting of a rigid spacer linked to two parallel cofacially disposed terpy‐M–X (M = Pd2+, Pt2+) units, which can vary in separation from 6.6 to 7.2 Å, have been used as molecular receptors and for self‐assembly with linear and triangular linkers to produce rectangles and trigonal prisms, respectively. Aromatic molecules form multiple host–guest adducts with the molecular cleft receptors and with the rectangles and trigonal prisms. Planar complexes of Pt2+ also form host–guest adducts. The forces that control this molecular recognition, namely, π‐π interactions, charge‐induced dipole interactions, charge‐charge forces, weak metal‐metal interactions and solvation effects, are discussed and assigned to the various adducts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Host-guest interactions template: the synthesis of a [3]catenane.

Formation of a [3]catenane containing dibenzo-24-crown ether wheels and a large dipyridiniumethane ring is templated by formation of a host-guest adduct between the [3]catenane and the external crown ether.