Chiral Cavity Research Articles

Concentration-Dependent Self-Assembly of a Novel Comb Oligomer Having Rigid Binaphthyl Macrocyclic Pendants

The synthesis and self-assembly of a comb Oligomer having rigid racemic binaphthyl macrocylic pendant groups are described. The coupling of two structural motifs at the molecular level, e.g., a nanometer-size chiral cavity, and a flexible polymeric backbone, cold lead to new opportunities in molecular recognition and separation. The macrocyclic monomers were synthesized followed by introduction of an acrylate side-group, and through free-radical polymerization, they yielded a comb oligomer. Most importantly, this novel oligomer can self-assemble into solid or hollow spheres when tetrahydrofuran (THF) solutions of the oligomer at different concentrations are dropped onto the surface of water. The morphology of the solid or hollow spheres was observed by TEM, ESEM and DLS.

Chiral Electrochemical Recognition by Very Thin Molecularly Imprinted Sol−Gel Films

Thin films with enantioselective properties for electrochemically active chiral probes were developed. Enantioselectivity was accomplished via molecular imprinting. The films were fabricated through the sol-gel technique and were spin-coated on ITO electrodes. The chiral selectivity recognition was detected using two enantiomer pairs: D- and L-3,4-dihydroxyphenylalanine (D- and L-dopa) and (R)- and (S)-N,N'-dimethylferrocenylethylamine [(R)-Fc and (S)-Fc]. A defined chiral cavity was obtained by selection of functional monomers that interact with the template molecule, followed by its removal. Chiral selection properties were measured by cyclic voltammetry and square wave voltammetry. For both template molecules, very good chiral recognition was revealed by electrochemical measurement. The nonspecific adsorption measured for reference nonimprinted films was negligible (less than 5%). Dopa imprinted films revealed both high sensitivity, by the detection of 1 nM (0.2 ppb) concentration, and excellent selectivity, when challenged with a series of catechol derivatives. Fc-imprinted films were able to detect ca. 2 ppm of the target molecule, with very good enantioselectivity and low nonspecific adsorption. To our knowledge, this is the first report of successful molecular imprinting of a ferrocene derivative.

Thermodynamic Study of Enantioseparation of Arylpropionic Acids with a Chiralcel OJ‐H Stationary Phase

Enantioseparation data of ketoprofen, fenoprofen, and ibuprofen have been obtained and thermodynamically analyzed. The Chiralcel OJ column was used for chiral separation. The mobile phases were 100/0, 95/5, and 90/10 v/v% hexane/2‐propanol mixtures with 0.5% acetic acid. The capacity factors of the solutes were measured at 25°C, 30°C, 35°C, 40°C, 45°C, and 50°C. The thermodynamic properties of solute transfer from the mobile to the stationary phase were critically analyzed in comparison with the thermodynamic properties obtained by the Chirex 3001 phase in methanol/water eluents. The well‐known enthalpic–entropic compensation is clearly valid for the systems studied in this research. The solute–Chiralcel OJ interactions of R‐ and S‐ibuprofen were found weaker than those of R‐ and S‐fenoprofen and ketoprofen, since ibuprofen is much less polar than others and subject to much weaker interactions with the stationary phase. Careful interpretation of the data revealed that the solute–Chiralcel OJ interaction is stronger than the solute–Chirex 3001 interaction. It is likely that the supramolecular structure of the Chiralcel OJ phase with chiral cavities provides more versatile functional and steric environments, to give stronger interactions and better chiral recognition and discrimination. There appeared extrema in the plots of ΔH 0 and ΔS 0 against eluent composition obtained in the Chiralcel OJ system. Adsorption of 2‐propanol to multiple sites with different priorities and different steric environments seems to cause such a phenomenon.

Synthesis and Properties of Chiral Molecular Clefts Related to Tröger's Base

The chiral cavities present in 2,3:6,7-dibenzo-9-oxabicyclonona-2,6-diene, dibenzobicyclo[b,f][3.3.1]nona-5a, 6a-diene-6,12-dione, bicyclo[3.3.1]nonane and dibenzobicyclo[b,f][1,5]diazocines are reminiscent of Tröger's base, which has been widely used as a molecular cleft in supramolecular chemistry. The synthetic methodology to provide key derivatives for elaboration into new supramolecular structures, efficient resolution methods, the introduction of additional recognition groups and applications in supramolecular chemistry of these structurally related molecular clefts are reviewed.

Enantioseparation and Chiral Recognition Mechanism of Two Novel Organic Phosphonate Derivatives on Chiral Stationary Phases

Direct enantiomeric resolution of two synthesized organic phosphonate derivatives [(2‐Chloro‐phenylamino)‐(2‐hydroxy‐phenyl)‐methyl]‐phosphonic acid diethyl ester (compound 1) and [(2‐Chloro‐phenyl)‐(4‐fluoro‐phenylamino)‐methyl]‐phosphonic acid diethyl ester (compound 2) has been achieved using hexane as the mobile phase with various alcohols as modifiers. The influence of the mobile phase composition and solute structure on the chiral separation was studied. It was found that compound 1 achieved good separation on (S,S)‐Whelk‐O1, cellulose tris(3,5‐dimethylphenylcarbamate) (CDMPC) and cellulose trisphenylcarbamate (CTPC) chiral stationary phases, while compound 2 could be separated on (R,R)‐3,5‐dinitrobenzoyl‐1,2‐diphenylethane‐1,2‐diamine((R,R)‐DNB‐DPEDA) and CDMPC chiral stationary phases. Interestingly, on cellulose derivative chiral stationary phases (CSPs), acidic additive was necessary for enantioseparation of compounds 1 and 2. The chiral recognition mechanism of (S,S)‐Whelk‐O1, (R,R)‐DNB‐DPEDA and cellulose derivative CSPs was explored. On (S,S)‐Whelk‐O1‐CSP, hydrogen‐bonding interactions play an important role in chiral recognition. On (R,R)‐DNB‐DPEDA‐CSP, the dipole‐dipole interactions and π‐π stacking are important to chiral discrimination. On (S,S)‐Whelk‐O1‐CSP and (R,R)‐DNB‐DPEDA‐CSP, a correlation is concluded between elution order and absolute configuration of the analytes. On cellulose CSPs, the inclusion and fitness of solute shape in the chiral cavity significantly contributed to the enantioseparation of solutes. Furthermore, as for the enantioseparation of compound 1, the hydrogen‐bonding interactions play an important role on CTPC, but play a minor role on CDMPC.

Chiral Crystal Structure of Racemic Binaphthyl Poly(ether ketone) Macrocycles

Summary: The crystal structure of rigid, hollow, racemic binaphthyl poly(ether ketone) macrocycles has been elucidated by single crystal X-ray analysis. Multitudinal interactions were identified within the chiral space group P212121. The structural analysis revealed that this macrocyclic compound contains an elliptic chiral cavity with a size of 9.80 × 5.18 Å, which is similar to that of cyclodextrins. The knowledge about the interaction sites and the structure of the binaphthyl-based macrocycle provides a unique opportunity to understand its molecular or chiral recognition properties. Space-filling representation of the single (R)-macrocycle.

Cholesterol-Armed Cyclens for Helical Metal Complexes Offering Chiral Self-Aggregation and Sensing of Amino Acid Anions in Aqueous Solutions

Cholesterol-armed cyclens worked as octadentate receptors for Na+, Ca2+, and Y3+ complexes in which four chiral cholesterol-functionalized sidearms were bundled and asymmetrically twisted above cyclen-metal complex platforms. Since the resulting helical metal complexes included chiral, hydrophobic cholesterol residues and charged, hydrophilic metal sites as well as asymmetric coordination geometries, they exhibited unique amphiphilic properties and provided chiral self-aggregates in aqueous solutions. Light scattering, fluorescence, and TEM characterizations demonstrated that Na+ complex with cholesterol-armed cyclen gave a particularly stable self-aggregate in aqueous solution and offered supramolecular environments effective for sensing and detection of amino acid anions. Various dansylamino acid derivatives (dansyl = 5-(dimethylamino)-1-naphthalenesulfonyl) were nicely accommodated in the helicate aggregates to give highly enhanced fluorescence signals, which could be detected by the naked eye at 10(-7) mol/L level. Their inclusion behaviors were analyzed by a Langmuir-type equation, indicating that enantiomer-selective inclusion occurred. MM/MD calculations and circular dichroism (CD) studies further suggested that cholesterol-armed cyclen helicates have chiral and hydrophobic cavities upon self-aggregation, in which the dansylamino acid anions were specifically accommodated. Since these helicates exhibited nonselective binding abilities in solvent extraction experiments of dansylamino acid anions, uncommon chiral recognition and sensing functions were generated by supramolecular alignments of the chiral metal helicates in the aqueous solutions.

Comparative Enantioseparation of 2‐Arylpropionic Acid Esters on Cellulose Derivative and (S,S)‐Whelk‐O 1 Columns

Cellulose‐derivative chiral stationary phases (CSPs) have been proven to be the most useful CSPs because of their versatility and capability. However, the exact chiral recognition mechanism on these CSPs is still unclear due to the complexity of these CSPs. In the present study, we attempt to compare the difference of the chiral recognition mechanism between cellulose‐derivative CSPs and (S,S)‐Whelk‐O 1 using ketoprofen esters, tropic acid esters, and racemic naproxen esters. The results revealed that alkoxy groups have great influence on the chiral recognition of 2‐arylpropionic acid esters on cellulose‐derivative CSPs or (S,S)‐Whelk‐O 1. From methyl ester to sec‐butyl ester, the chiral selectivity (α) is systematically changed on (S,S)‐Whelk‐O 1, whereas it does not follow any particular trend on cellulose‐derivative CSPs, suggesting that the attractive interactions between CSP and solute were the predominant factor for the chiral recognition on (S,S)‐Whelk‐O 1, although the inclusion and steric fitness of solutes into the chiral cavities might be the dominant chiral recognition mechanism for cellulose‐derivative CSPs. With several exceptions, there exists some kind of correlation between the ester kind and a different kind of cellulose‐derivative CSP. The influence of mobile phase modifier on the enantioseparation of 2‐arylpropionic acid esters on the cellulose‐derivative chiral columns was also extensively studied. Four types of influence resulting from using different alcoholic modifier in mobile phase were observed. The influence of alcoholic modifier on the enantioseparation was mainly through the alteration of steric environment of chiral cavities and this influence is solute dependent. Furthermore, the results suggested that the hydrogen‐bonding interaction between solute and CSP might not be important for the chiral recognition of ketoprofen esters, tropic acid esters, or racemic naproxen esters on cellulose tris(3,5‐dimethylphenylcarbamate) (CDMPC).

A Chiral Molecular Bowl Containing Three Ferrocenes: Synthesis and Its Efficiency in an Optical Resolution of 1,1′‐Bi‐2‐naphthol.

Condensation reaction of 1,1'-ferrocenedicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane affords a novel bowl-shaped macrocycle with a chiral concave cavity which exhibits a remarkable ability as a host material for the enantioselective enclathration of 1,1'-bi-2-naphthol.

Synthesis of polymer gel with chiral helical cavity by molecular imprinting using bifunctional vinyl monomers

The molecular imprinting method was applied for synthesizing gels with a chiral helical cavity using various bifunctional vinyl monomers, such as α-(benzyloxymethyl)acrylic acid derivatives as a monomer, and one-handed helical (+)-poly(diphenyl-2-pyridylmethyl methacrylate) as a template. The chiral gels were almost quantitatively prepared after removal of the template polymer by hydrolysis of the ester groups. The obtained gels exhibited chiral resolution powers toward various racemates, such as trans-stilbene oxide and Tröger's base, and the substituents on the phenyl group of the monomer significantly affected the recognition ability. The observed separation factors were higher than those of the gels prepared from the mono-functional vinyl monomer, methacrylic acid.

Metal-complex assemblies constructed from the flexible hinge-like ligand H2bhnq: structural versatility and dynamic behavior in the solid state.

Novel metal-complex assemblies constructed from the flexible hinge-like ligand H(2)bhnq (H(2)bhnq=2,2'-bi(3-hydroxy-1,4-naphthoquinone)) have been synthesized. The X-ray crystal structures of these compounds reveal that four types of architectures are accessible by variation of the metal ions. In copper(II) compounds 1-3, the chelating bhnq(2-) ions bridge copper(II) centers to form one-dimensional zigzag chains. The chains of 1-3 are arranged by hydrogen-bonding interactions and stacking interactions to produce porous structures. Cobalt(II) and zinc(II) compounds 4 and 5 form one-dimensional helical chains. In 4 and 5, the crystal packing induces spontaneous resolution of the helical chains with chiral cavities formed perpendicular to the helices. Nickel(II) compounds 6 and 7 form cyclic tetramers. The fourth architecture, a dimer (compound 8), is obtained by the reaction of zinc(II) and bhnq(2-) in MeOH. In these compounds, changes of the dihedral angles and the metal-coordination mode of the bhnq(2-) ion induce the structural versatility. The assemblies of the zigzag chains of the copper(II) compounds exhibit reversible vapochromic behavior. UV/Vis, powder X-ray diffraction, EPR, and adsorption isotherm measurements indicate that this vapochromic behavior is based on the hinge-like flexibility of the bhnq(2-) ion.

Enantioselective Guest Binding and Dynamic Resolution of Cationic Ruthenium Complexes by a Chiral Metal−Ligand Assembly

A supramolecular metal-ligand assembly encapsulates a variety of cationic half-sandwich ruthenium complexes. Due to the chirality of both host and guest, chiral recognition is observed with diastereomeric excesses up to 70%. The chiral cavity can be used to carry out a dynamic resolution of the rapidly equilibrating enantiomers of the chiral organometallic guest.

A chiral molecular bowl containing three ferrocenes: synthesis and its efficiency in an optical resolution of 1,1'-bi-2-naphthol.

Condensation reaction of 1,1'-ferrocenedicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane affords a novel bowl-shaped macrocycle with a chiral concave cavity which exhibits a remarkable ability as a host material for the enantioselective enclathration of 1,1'-bi-2-naphthol.

Self-assembly behavior of inclusion complex formed by b-cyclodextrin with a-aminopyridine

An inclusion complex ( 1 ) has been prepared by β-cyclodextrin with α-aminopyridine. The result of X-ray crystallographic analyses showed that the α-aminopyridine molecules in the β-cyclodextrin cavities possess two opposite orientations, i.e. the amine group of a-aminopyridine pointing to the primary side ( 1a , occupancy: 41.2%) or the secondary side ( 1b , occupancy: 58.8%) of b-cyclodextrin, forming two scalelike supramolecular aggregations. The studies of 2D NMR and circular dichroism spectra indicated that the α-aminopyridine molecule is deeply embedded in the β-cyclodextrin cavity to form host-guest inclusion complex, showing a circular dichroism spectrum induced by the chiral cavity of cyclodextrin. The results obtained are helpful for understanding the molecular recognition and aggregation mechanism between the host and guest.

Trinuclear to dinuclear: a radii dependence lanthanide(III) self-assembly coordination behavior of an amide-type tripodal ligand.

Lanthanide nitrate complexes with the heptadentate ligand L (6-[2-(2-(diethylamino)-2-oxoethoxy)ethyl]-N,N,12-triethyl-11-oxo-3,9-dioxa-6,12-diazatetradecanamide), [Ln(2)L(NO(3))(6)] (Ln = La, Nd, Sm, Eu, Ho), have been prepared and characterized. The X-ray crystallographic studies show that, in [La(2)L(NO(3))(6)(H(2)O)].H(2)O (1), two complex cations [LaL(H(2)O)](3+) are linked by a hexanitrato anion [La(NO(3))(6)](3)(-) and form a trinuclear cation. In [Nd(2)L(NO(3))(6)(H(2)O)].CHCl(3).1/2CH(3)OH.1/2H(2)O (2), one complex cation [NdL(H(2)O)](3+) and a hexanitrato complex anion [Nd(NO(3))(6)](3)(-) are linked by a bridging NO(3)(-) to form a dinuclear complex. In both complexes, the bridging nitrate is an unusual tetradentate ligand. The metal ions are 12-coordinated in hexanitrato anions and 10-coordinated in complex cations. The chainlike supramolecular structures of La(3+) complex are parallel and have no hydrogen bonds in between, while, in the Nd(3+) complex, a chiral cavity is formed by hydrogen bonds between two adjacent supramolecular chains. These influences are further investigated by assessing the separation efficiency of L and (1)H NMR spectra of its lanthanide nitrate mixtures in solution.

Monophosphorylation of 1,4:3,6‐Dianhydro‐D‐mannitol.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Structural Variation and Molecular Recognition Using Inclusion Compounds of Crystalline Dipeptides

AbstractFor Abstract see ChemInform Abstract in Full Text.

General Method for Chiral Imprinting of Sol−Gel Thin Films Exhibiting Enantioselectivity

Chirally imprinted sol−gel thin films were fabricated through the molecular imprinting technique. The films were spin coated on glass plate substrates. Enantioselective discrimination of these films was observed toward three different templates. In each case a different enantiomer pair was selected as a template and a sol mixture was tailored accordingly. By extracting the template molecule a defined chiral cavity was created. The enantiomer pairs were (R)- and (S)-propranolol, (R)- and (S)-2,2,2-trifluoro-1-(9-anthryl) ethanol, and d- and l-3,4-dihydroxyphenylalanine (d- and l-dopa). Selective adsorption properties of the resulted films toward the imprinted molecules were measured by radioactive and fluorescence analysis. In all cases, preferred adsorption of one enantiomer was revealed. This preference was due to configuration match between the cavity and the adsorbed molecule. Nonspecific adsorption was remarkably low and was measured for reference nonimprinted films.

Effects of alcohol mobile-phase modifiers on the structure and chiral selectivity of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase

Following a previous publication, the present paper reports additional results on the effects of alcohol mobile-phase modifiers on the structure and chiral selectivity of amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) chiral stationary phase (CSP). Solid-state NMR ( 1 H/ 13 C CPMAS) was utilized to identify and compare structural differences in Chiralpak AD caused by the various alcohol mobile-phase modifiers, many of which were not studied in the previous publication. The influences of the various alcohol modifiers (in hexane-based mobile phase) on the structure and chiral selectivity of the CSP were studied and compared. CPMAS spectra of Chiralpak AD flushed with the mobile phases displayed clear evidence of solvent incorporation into the CSP. When alcohol modifiers with varying size and bulkiness were used in the mobile phase, differences in structure and chiral selectivity were observed on Chiralpak AD based on solid-state NMR and chromatographic data. The change of t-butanol concentration in the t-butanol/hexane mobile phase caused changes of structure and chiral selectivity of the Chiralpak AD. These data further support our belief that the different chiral selectivities of the CSP associated with the use of different alcohol modifiers are due to different alterations of the steric environment of the chiral cavities in the CSP by the different mobile-phase modifiers.

Enantiomerically Pure Phenanthroline or Bipyridine Containing Macrocycles: A New Class of Ligands for Asymmetric Catalysis.

AbstractFor Abstract see ChemInform Abstract in Full Text.