Chiral Calix Research Articles

Highly selective and sensitive chiral recognition to deoxynucleosides by calixarene oligomers modified silver nanoparticles

Efficient enantiomeric sensing to deoxynucleosides by a simple method is of great importantance and remains a challenge in biochemical field. In this paper, three chiral calixarene oligomers (CA[n]P, n=4, 6, 8) were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR), UV–vis spectrophotometry, circular dichroism spectroscopy (CD), X-ray Powder Diff ;raction (XRD), X-ray Photoelectron Spectroscopy (XPS), Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS), 19F Nuclear Magnetic Resonance (NMR) and scanning electron microscopy (SEM). After that, the chiral calixarene oligomers capped silver nanoparticles (CA[n]P-Ag NPs, n=4, 6, 8) were prepared and characterized by FT-IR, UV–vis spectrophotometry, CD and dynamic light scattering (DLS). By using the as prepared CA[n]P-Ag NPs (n=4, 6, 8), highly selective and sensitive chiral recognition to deoxynucleosides was realized and demonstrated by UV–vis and CD. The color of the CAP-Ag NPs changes from yellow to red in the presence of β-L-2′-deoxycytidine (L-dC) or β-L-2′-deoxythymidine (L-dT) at a certain time, but not of their corresponding enantiomer β-D-2′-deoxycytidine (D-dC) or β-L-2′-deoxythymidine (D-dT). Moreover, the chiral recognition ability of CA[n]P-Ag NPs (n=4, 6, 8) toward L-deoxynucleosides was found to be in the order of CA[8]P-Ag NPs＞CA[6]P-Ag NPs＞CA[4]P-Ag NPs. This convenient method shows forceful prospect in developing biochemical sensors and has the potential application in enantiomeric recognition and separation of deoxynucleosides.

25‐Propyloxy‐26,27‐dibenzoyloxy‐calix[4]arene as Precursor for the Synthesis of Inherently Chiral Calixarenes

AbstractThis paper shows that 25‐propyloxy‐26,27‐dibenzoyloxy‐calix[4]arene can be a convenient precursor for the formation of inherently chiral configuration on the calixarene platform. The methods for sequential regioselective debenzoylation and electrophilic substitution on the upper rim were developed. The inherently chiral calix[4]renes with two and three different functional groups on the upper rim were synthesized.

Mononitration of a Calix[4]arene Methylene Bridge: Synthesis and Preliminary Catalysis Performances of Bridging Chiral p-tert-Butylcalix[4]arenes with a Monoamino Bridge Substituent in a 1,3-Alternate Conformation.

In order to prepare bridging chiral p-tert-butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with tert-butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization. After further modification and diastereoisomeric resolution, a pair of bridging chiral p-tert-butylcalix[4]arenes with a monoamino bridge substituent were produced from the bridge-mono-nitrated calix[4]arene. Their preliminary catalysis results in the Henry reaction show good catalytic activities (up to 95% yield) and still low but obviously enhanced enantioselectivities (up to 22.3% ee from 7a, 6% ee from 1), which confirms that the structural transformation indeed improves asymmetric catalysis performances of bridging chiral calix[4]crown-5 amines in a 1,3-alternate conformation.

Self-sorting behavior in supramolecular fullerene polymerization directed by host-guest complexation between calix[5]arene and C60.

We describe self-sorting supramolecular polymerization that uses chiral calix[5]arene hosts and a dumbbell-shaped fullerene guest. In a solution containing the racemic host and the guest, the (S)-host and the (R)-host preferably formed their homomeric complexes to form helical supramolecular fullerene polymers in a self-sorting manner. The self-sorting behavior has been studied using diffusion-ordered 1H NMR (DOSY) and circular dichroism (CD) studies. The present findings show that it is possible to accomplish controlled supramolecular polymerization.

Facile synthesis of a C4-symmetrical inherently chiral calix[4]arene.

Inherently chiral calix[4]arenes with C4-symmetry are extremely rare and difficult to synthesise, severely hampering any effort to expand on their potential as chiral supramolecular catalysts and building blocks. Herein we report a reaction of a tetracarbamate calix[4]arene with NBS which results in a high yield of an inherently chiral calix[4]arenes with C4-symmetry. Furthermore, employing a chiral N-Boc proline moiety allows for separation of the diastereomers formed, thus obtaining the pure enantiomers after hydrolysis. The enantiomers could be assigned based on the CD spectra and DFT calculated values.

Study on the Influence of Chirality in the Threading of Calix[6]arene Hosts with Dialkylammonium Axles

The influence of chirality in calixarene threading has been studied by exploiting the “superweak anion approach”. In particular, the formation of chiral pseudo[2]rotaxanes bearing a classical stereogenic center in their axle and/or wheel components has been considered. Two kind of pseudo[2]rotaxane stereoadducts, the “endo-chiral” and “exo-chiral” ones, having the stereogenic center of a cationic axle inside or outside, respectively, the calix-cavity of a chiral calixarene were preferentially formed with specifically designed chiral axles by a fine exploitation of the so-called “endo-alkyl rule” and a newly defined “endo-α-methyl-benzyl rule” (threading of a hexaalkoxycalix[6]arene with a directional (α-methyl-benzyl)benzylammonium axle occurs with an endo-α-methyl-benzyl preference). The obtained pseudorotaxanes were studied in solution by 1D and 2D NMR, and in the gas-phase by means of the enantiomer-labeled (EL) mass spectrometry method, by combining enantiopure hosts with pseudoracemates of one deuterated and one unlabeled chiral axle enantiomer. In both instances, there was not a clear enantiodiscrimination in the threading process with the studied host/guest systems. Possible rationales are given to explain the scarce reciprocal influence between the guest and host chiral centers.

Regioselective formation of the quinazoline moiety on the upper rim of calix[4]arene as a route to inherently chiral systems

N-acyl aminocalix[4]arenes were cyclized with nitriles to afford the expected quinazolines only in the case ofpara-substituted series. This strategy represents a new route to inherently chiral calixarenes potentially useful as fluorescent receptors.

Attempted synthesis of a meta-metalated calix[4]arene.

An evidence for the formation of a rare meta-metalated inherently chiral calix[4]arene is described. Our strategy involved using a mesoionic carbene to direct C–H activation, but proved to form an unexpectedly unstable intermediate that was identified through high-resolution mass spectrometry. On route to our target, a new optimized method to mononitrocalix[4]arenes was developed, including optimized and high yielding transformations to azide and 1,2,3-triazole derivatives which may have application in other areas of research.

A phenyl glycinol appended calix[4]arene film for chiral detection of ascorbic acid on gold surface

This paper describes the synthesis of new chiral calix [4]arene derivative having (R)-2-phenylglycinol moiety (compound 6), and its chiral recognition studies for ascorbic acid (AA) enantiomers by using Quartz Crystal Microbalance (QCM). Initial experiments indicated that the outstanding selective chiral recognition (α) was observed as 2.61 for l-enantiomer of AA. The sensitivity (S) and the limit of detection (LOD) values for L-AA were calculated as 0.0226 Hz/μM and 0.63 μM, respectively. Furthermore, the sorption behavior and mechanism of AA onto compound 6 film were evaluated and the sorption data exhibited a good correlation with the Freundlich isotherm models. The maximum uptake of L-AA by the sensor was found as 5895.76 mg/g. In conclusion, chiral recognition of AA enantiomers as real-time, sensitive, selective and effective was performed by a calixarene derivative coated QCM sensor.

Rapid and real-time detection of arginine enantiomers by QCM sensor having a Calix[4]arene receptor bearing asymmetric centers

This paper describes the sensing studies of a chiral calix[4]arene receptor (5) having (R)-2-phenylglycinol moiety for arginine enantiomers (D-/L-arginine) by using Quartz Crystal Microbalance (QCM) technique. The initial experiments have revealed that the chiral calix[4]arene 5 coated QCM (CCC-QCM) sensor showed good sensing for arginine enantiomers, such that it has exhibited higher sensing towards D-arginine than that of L-arginine. It has been determined that the sensitivity, limit of detection values of CCC-QCM sensor for the D-/L-arginine solutions as 0.024/0.023 Hz/μM and 0.38/1.29 μM, respectively. On the other hand, the racemic mixture studies were optimized using the response surface methodology with central composite design. Consequently, it has been demonstrated that the QCM sensor modification with a calix[4]arene receptor bearing asymmetric centers provided rapid, real-time, sensitive and effective sensing of arginine enantiomers.

Novel chiral Oxa-bridged Calix[2]arene[2]triazine derivatives as NMR chiral reagents for enantioselective recognition of α-racemic carboxylic acids

A new family of chiral tetraoxacalix[2]arene[2]triazine receptors (2a–2c) have been synthesized efficiently in 69–73% yields. By 1H NMR spectroscopy, the chiral enantiodiscrimination ability of novel hosts against a series racemic carboxylic acids were examined. The chiral calix[2]arene[2]triazine-based compounds were found to have good enantiomeric recognition ability to racemic carboxylic acids. We also observed that the tetraoxacalix[2]arene[2]triazine derivative 2c is a more versatile chiral solvating agents than 2a and 2b, as 2c shows a better performance for the determination of the enantiomeric excess. The molar ratio of the each enantiomers of guest molecules with receptors were examined by using Job plots, respectively. The graphics show that the hosts form 1:1 complexes with all of the guests.

Selective chiral recognition of alanine enantiomers by chiral calix[4]arene coated quartz crystal microbalance sensors.

We describe the synthesis of new chiral calix[4]arene derivatives having (R)-1-phenylethylamine, (S)-1-phenylethylamine, (R)-2-phenylglycinol, and (S)-2-phenylglycinol moieties, and chiral recognition studies for enantiomers of some selected α-amino acid derivatives such as alanine, phenylalanine, serine, and tryptophan using a quartz crystal microbalance (QCM). Initial experiments indicated that the highest selective chiral recognition factor was 1.42 for alanine enantiomers. The sensitivity, limit of detection, and time constant for L-alanine were calculated as 0.028 Hz/μM, 60.9 μM, and 36.2 s, respectively. The results indicated that real-time, sensitive, selective, and effective chiral recognition of alanine enantiomers was achieved with a QCM sensor coated with a chiral calix[4]arene derivative having (R)-2-phenylglycinol moieties.

QCM sensors coated with calix[4]arenes bearing sensitive chiral moieties for chiral discrimination of 1-phenylethylamine enantiomers

This article describes the enantiomeric discrimination properties of new chiral calix[4]arene derivatives bearing (S)-/(R)-1-phenylethylamine moieties (5a and 5b, respectively) towards the 1-phenylethylamine enantiomers on QCM surface. Initial experiments demonstrated that the 5b coated QCM sensor was the most effective sensing material for enantiomeric discrimination of (R)-/(S)-1-phenylethylamine by exhibiting much more sensing ability towards (R)-enantiomer than (S)-enantiomer. Sensitivity, detection limit and time constant of the 5b coated QCM sensor has been were calculated as 0.082 Hz/µM, 2.7 µM, and 319.2 s, respectively. Additionally, effects of calixarene content and different coating technique on enantiomeric discrimination, and Langmuir and Freundlich isotherms of the sensing results also were studied. As a result, it has been demonstrated that the coating of QCM sensor with a chiral calix[4]arene (5b) having (S)-1-phenylethylamine moieties provides substantially enantiomeric discrimination of 1-phenylethylamine enantiomers.

Chiral phosphorus-containing calixarenes

Phosphorus-containing inherently chiral calix[4]arenes as well as calix[4]arenes substituted with phosphinoferrocene chiral groups at the lower rim are described. Stereoselective synthesis, structure, and catalytic properties of the chiral calixarenes are discussed.

Synthesis of enantiomerically pure inherently chiral calix[4]arenes using the meta-substitution strategy

A meta-substituted aminocalix[4]arene 4 immobilized in the cone conformation was prepared via mercuration of the starting tetra-propoxy derivative, followed by nitrosation and reduction reactions. Acylation of the amino group by chiral amino acid residues ((S)-N-trifluoroacetyl-Ala or (S)-N-trifluoroacetyl-Phe) allowed for the preparation of diastereomeric amides that were separated by preparative TLC on silica gel. Subsequent cyclization under Bischler-Napieralski reaction conditions yielded calixarenes 7b and 7c bearing an oxazole moiety in the meta position instead of the expected upper rim-bridged compounds. The reaction sequence represents a straightforward approach towards enantiomerically pure inherently chiral calix[4]arene derivatives (without HPLC separation steps). The absolute configuration of the enantiomers were confirmed by single crystal structure determination (X-ray).

Chiral calixarene and resorcinarene derivatives. Conical cavities substituted at their upper rim by two phosphito units and their use as ligands in Rh-catalysed hydroformylation

Two chiral diphosphites, (S,S)-5,17-bis(1,1′-binaphthyl-2,2′-dioxyphosphanyloxy)-25,26,27,28-tetrapropyloxycalix[4]arene (1) and (S,S)-5,11-bis(1,1′-binaphthyl-2,2′-dioxyphosphanyloxy)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetrapentylresorcin[4]arene (2), each based on a conical cavity, were synthesised and assessed in the rhodium-catalysed hydroformylation of vinyl arenes. Under optimised conditions, both ligands led to high proportions of branched aldehyde (b/l = 8.1) in the hydroformylation of styrene. The observed enantioselectivity was considerably higher for 1 than 2 (ee 89% vs. 50%), this being consistent with the easy formation of chelated intermediates with 1 (chelate formation is prevented with 2), in which the embracing ligand enables an efficient chirality transfer to the catalytic centre.

Macroscopic Chiral Recognition by Calix[4]arene-Based Host-Guest Interactions.

Chiral recognition as an intrinsic process of life, plays a crucial role in chemical systems, and further forms various architectures in the resulted functional materials. So far, relevant studies were focused on the recognition of chiral molecules. However, weak chiral interactions transformed into macroscopic recognition, for example, for chiral drug droplets, is much more crucial due to its applicability in controlling the drugs' selective delivery and for their enantiomer separation. In this report, chiral calix[4]arene was introduced onto a surface for the selective recognition of (S)-naproxen droplet through host-guest interactions.

Construction of an electrochemical chiral interface by the self-assembly of chiral calix[4]arene and cetyltrimethylammonium bromide for recognition of tryptophan isomers

Molecular self-assembly offers an effective route for the rational design of chiral sensing devices. Here, cetyltrimethylammonium bromide (CTAB) was linked with the chiral calix[4]arene (CCA) via ion–dipole interactions and then an electrochemical chiral interface was constructed from the resulting self-assembled CCA-CTAB. Highly efficient recognition of tryptophan (Trp) isomers (Il-Trp/Id-Trp = 18.96) was achieved with the CCA-CTAB self-assembled interface. Possible mechanisms were proposed, based on density functional theory (DFT) and wettability measurements. Finally, the resulting electrochemical chiral interface was used to analyze the precise levels of l- and d-Trp in a racemic mixture of Trp isomers.

Recent applications of chiral calixarenes in asymmetric catalysis.

The use of calixarenes in asymmetric catalysis is receiving increasing attention due to their tunable three-dimensional molecular platforms along with their easy syntheses and versatile modification at the upper and lower rims. This review summarizes the recent progress of synthesis and use of chiral calixarenes in asymmetric syntheses which emerged later than 2010.

Synthesis of an Enantiomerically Pure Inherently Chiral Calix[4]Arene Phosphonic Acid and Its Evaluation as an Organocatalyst.

A facile method for the preparation of enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-7 in four steps starting from the readily available and previously synthesized (cS)-enantiomer of calix[4]arene acetic acid 1 or its methyl ester 2 was developed. The first tests of this unique calixarene Brönsted acid with inherent chirality in organocatalysis of the aza-Diels-Alder reaction of imines with Danishefsky's diene and epoxide ring opening by benzoic acid were performed. The calixarene phosphonic acid (cR,pR)-7 shows good catalytic activities but with low enantioselectivities in these reactions.