Chiral Moiety Research Articles

Chiral metallic anticancer drugs: A brief-review

Chiral metallic drugs are becoming the hottest point of discussion in the field of medicinal chemistry. As we know that more than 80% drugs are chiral in nature, and prescribed in the racemic form. The main problem with chiral drugs is the different biological activities of different enantiomers. This is because the human body has a chiral environment, as there is the presence of protein, carbohydrates, enzymes, and other chiral macromolecules. Hence, if a chiral anticancer drug is being prescribed to the patient in the racemic form, it means two or more drugs are being prescribed. Therefore, the chiral separation and analysis of chiral anticancer drugs are important for improving the quality of chiral drug medication. Many metal complexes are used as anticancer drugs, but the conditions become more critical if they have chirality or a chiral moiety, because of which they exist in two or more forms. Because of the presence of chirality or chiral moiety, the complex of metals is termed a chiral metallic complex. Of course, the enantioseparation of the chiral metallic complexes must be done before their prescription. Enantioseparation of the chiral metallic complex will not only provide a pharmaceutically active form to the patient but also reduce the side effects caused by the racemic mixture. Hence, the accessible article reviews the chiral metallic complexes having ruthenium, osmium, palladium, gold, silver, and platinum, etc. as central metal atoms. Besides, the future perspectives regarding the chiral metallic anticancer drugs and the role of their enantioseparation are also discussed.

Two bridge-particle-mediated RET between chiral molecules.

The problem of resonance energy transfer between a pair of chiral molecules mediated by two electrically polarizable bridging particles is solved using molecular quantum electrodynamics theory. In this framework, a single virtual photon propagates between any two-coupled entities and is responsible for the conveyance of excitation energy from the emitter to the absorber. Electric dipole and quadrupole, and magnetic dipole couplings linear in the Maxwell fields are employed for donor and acceptor, while each mediator scatters two virtual photons and responds quadratically to the electric displacement field via its electric dipole polarizability. This enables fourth-order diagrammatic perturbation theory to be used to compute the probability amplitude for the process. Individual multipole moment contributions to the Fermi golden rule rate are then extracted for oriented and isotropic systems. Discriminatory transfer rates arise when either the donor or the acceptor are electric-magnetic dipole and the other has a pure multipole moment, or when both are chiral, with mixed electric dipole-quadrupole contributions vanishing in the fluid phase. The bridge-mediated transfer rate is found to be a maximum for a collinear geometry. Moreover, a multi-level model of the mediator is necessary for energy migration. Asymptotically limiting rates for arbitrary and collinear geometries are also obtained for one center purely electric dipolar and the other purely quadrupolar, or both donor and absorber purely quadrupolar. Understanding is gained of radiationless and radiative transfer mechanisms between chiral moieties in a dielectric medium.

Recent advances in chiral aggregation-induced emission fluorogens

• Chiral AIEgens can identify chiral molecules visually based on color change and precipitation reaction, quantitatively analyze chiral molecules, demonstrating its high selectivity, sensitivity and accuracy in chiral identification. • The CPL asymmetry factor (glum) of chiral AIE fluorogens (AIEgens) can reach 1.42, which is very close to the theoretical value of 2. • The combination of chiral elements and luminescent groups promotes their adoption in the field of organic CPL materials. • We have summarized the recent advances of chiral AIEgens in both chiral molecule recognition and circularly polarized organic light-emitting diode. As a flourishing research field, we believe that a detailed and timely literature collection of this field is highly desirable for the chemistry and material community. Over the past decade, aggregation-induced emission (AIE) molecules have played a pivotal role in bioimaging, anti-microbial, and photodynamic therapy, and have been at the forefront of several disciplines worldwide. When combined with chiral moieties, they can easily collide with dazzling sparks and exhibit exceptional and unique advantages. In the application of chiral recognition and measurement of enantiomeric excess, it can identify chiral molecules visually based on color change and precipitation reaction, quantitatively analyze chiral molecules while determining the enantiomeric composition based on the fluorescence intensity change at different wavelengths, and obtain two parameters about chiral molecules from one measurement, thereby demonstrating its high selectivity, sensitivity and accuracy in chiral identification. In the field of organic circularly polarized luminescent (CPL) materials, the asymmetry (g lum ) of common organic light emitting elements is usually between 10 −5 and 10 −2 , whereas the CPL asymmetry factor (g lum ) of chiral AIE fluorogens (AIEgens) can reach 1.42, which is very close to the theoretical value of 2. Therefore, the combination of chiral elements and luminescent groups promotes their adoption in the field of organic CPL materials. Herein we have summarized the recent applications of chiral AIEgens in both chiral molecule recognition and circularly polarized organic light-emitting diode (CP-OLED) in order to provide future researchers with a more comprehensive and detailed understanding of chiral AIEgens and to encourage more scientists to contribute to the development of AIEgens.

Tunable Multicolor Circularly Polarized Luminescence via Co-assembly of One Chiral Electron Acceptor with Various Donors

Tunable Multicolor Circularly Polarized Luminescence via Co-assembly of One Chiral Electron Acceptor with Various Donors

Cu(II)‐Amino Acid Ionic Liquid Surfactants: Metallovesicles as Nano‐Catalytic Reactors for Cross Dehydrogenative Coupling Reaction in Water

AbstractUtilization of the water as a reaction medium is very challenging due to the organic molecules insolubility in the aqueous medium. Still, self‐assembled structures like micelles and vesicles can act as nanoreactors to perform the organic reactions in water. In our efforts to achieve a chemical reaction in water, we have synthesized sustainable Cu (II) based amino acid (phenylalanine or valine) ionic liquid surfactants [AAC12]2[CuCl4], constructed their metallovesicles, and utilized these as nano‐catalytic reactors for C−C bond formation in the propargyl amines under the oxidative conditions. Aggregation of [AAC12]2[CuCl4] in an aqueous medium was studied using surface tension, pyrene fluorescence, and specific conductivity measurements. TEM and DLS analysis confirmed the formation of metallovesicles. [AAC12]2[CuCl4] metallovesicles acted as multitasking nanoreactors to provide a bio‐based template, water as a solvent, no additional catalyst to perform the reaction, and high yield (up to 94 % in low Cu(II) 0.012 mol%). Furthermore, The retention in the chirality of amino acid is observed in [AAC12]2[CuCl4], which can be a promising approach for one‐pot synthesis of chiral moieties in a greener way for future pharmaceutical manufacturing and other Cu(II) catalyzed reactions.

A case of antiferrochirality in a liquid crystal phase of counter-rotating staircases

Helical structures continue to inspire, prompted by examples such as DNA double-helix and alpha-helix in proteins. Most synthetic polymers also crystallize as helices, which relieves steric clashes by twisting, while keeping the molecules straight for their ordered packing. In columnar liquid crystals, which often display useful optoelectronic properties, overall helical chirality can be induced by inclusion of chiral chemical groups or dopants; these bias molecular twist to either left or right, analogous to a magnetic field aligning the spins in a paramagnet. In this work, however, we show that liquid-crystalline columns with long-range helical order can form by spontaneous self-assembly of straight- or bent-rod molecules without inclusion of any chiral moiety. A complex lattice with Fddd symmetry and 8 columns per unit cell (4 right-, 4 left-handed) characterizes this “antiferrochiral” structure. In selected compounds it allows close packing of their fluorescent groups reducing their bandgap and giving them promising light-emitting properties.

Chiral functionalization of solid surfaces with amino acid derivatives: diazonium grafting regulated by enantioselective processes.

Chiral inorganic nanostructures are essential for many enantioselective processes. It is possible to bestow chirality on otherwise achiral inorganic materials, via covalent functionalization of their surfaces with chiral organic molecules. However, controlling the degree of covalent functionalization is challenging, and there is an urgent need to find new avenues that can be applied to attach chiral moieties on different types of surfaces. By taking advantage of the versatility of diazonium chemistry, here we present a combined SPM/Raman study of the covalent grafting of amino acid-derived molecules on two different solid surfaces, with the intention to evaluate the effect of chiral reductants, chirally functionalized surfaces and chiral solvents on the chiral functionalization of solid surfaces. We show that the all three chiral species have an effect on the grafting of amino acid derivatives on solid surfaces, but affect the covalent attachment in different fashions. With a survey of the different aspects at play in chiral functionalization of solid surfaces, this study may offer a potential solution for the controlled production of many chiral nanostructures, and might also shine some light on the understanding of enantiospecific processes on inorganic crystalline surfaces.

Chiral Flavonoids as Antitumor Agents.

Flavonoids are a group of natural products with a great structural diversity, widely distributed in plant kingdom. They play an important role in plant growth, development and defense against aggressors. Flavonoids show a huge variety of biological activities such as antioxidant, anti-inflammatory, anti-mutagenic, antimicrobial and antitumor, being able to modulate a large diversity of cellular enzymatic activities. Among natural flavonoids, some classes comprise chiral molecules including flavanones, flavan-3-ols, isoflavanones, and rotenoids, which have one or more stereogenic centers. Interestingly, in some cases, individual compounds of enantiomeric pairs have shown different antitumor activity. In nature, these compounds are mainly biosynthesized as pure enantiomers. Nevertheless, they are often isolated as racemates, being necessary to carry out their chiral separation to perform enantioselectivity studies. Synthetic chiral flavonoids with promising antitumor activity have also been obtained using diverse synthetic approaches. In fact, several new chiral bioactive flavonoids have been synthesized by enantioselective synthesis. Particularly, flavopiridol was the first cyclin-dependent kinase (CDK) inhibitor which entered clinical trials. The chiral pool approaches using amino acid as chiral building blocks have also been reported to achieve small libraries of chrysin derivatives with more potent in vitro growth inhibitory effect than chrysin, reinforcing the importance of the introduction of chiral moieties to improve antitumor activity. In this work, a literature review of natural and synthetic chiral flavonoids with antitumor activity is reported for the first time.

Synthesis and mesomorphic properties of new organosiloxane chiral calamitic liquid crystals

A new chiral calamitic compound consisting of a phenyl core that is connected through ester linkers to a benzoate carrying a chiral (S)-2-methylbutoxy group at one side and a biphenyl carboxylate with an undecenyloxy chain at other side has been synthesized. Additionally, the siloxane substituted derivatives and a dimer with these two identical chiral calamitics linked by a disiloxane spacer have been obtained via hydrosilylation reaction to study the effect of combining the chiral moiety and siloxane segments within the same structure on liquid crystalline properties. The chiral calamitic compound and derivatives with a siloxane end-group or a siloxane spacer have been characterized using classical spectroscopic methods (1H NMR, 13C NMR, 29Si NMR and MS) and elemental analysis (EA). The liquid crystalline properties of all new compounds were investigated by differential scanning calorimetry, optical polarizing microscopy, X-ray scattering and electro-optic methods. With the introduction of a siloxane end-group to the vinyl-terminated calamitic compound exhibiting enantiotropic chiral nematic phase (N*) and chiral tilted smectic phase (SmC*), the occurrence of stable smectic phase was strongly promoted. In a similar way, the dimer with two identical calamitic mesogens connected by a disiloxane spacer exhibited a wider smectic mesophase interval in addition to the presence of N* mesophase. The new mesogens exhibit a ferroelectric switching with PS of around 200 nC cm−2 in their chiral tilted smectic (SmC*) mesophase range. The transition temperatures of organosiloxanes are considerably lower than that of olefinic precursor.

The Thermogel Chronicle─From Rational Design of Thermogelling Copolymers to Advanced Thermogel Applications

ConspectusTemperature responsive supramolecular hydrogels, also known as thermogels, are produced by the self-assembly of amphiphilic copolymers in solution following temperature stimulus. They are a class of high caliber novel materials possessing highly attractive properties such as injectability, ability to undergo temperature controlled reversible sol–gel phase transitions, high biocompatibility, and tunable biodegradability. Much research vigor has been dedicated to designing advanced amphiphilic copolymers and investigating their molecular interactions in order to enhance the properties of the thermogelling systems and expand the scope of their applications. As such, thermogelling systems have since become well established in the field of sustained localized drug or protein delivery and have also been demonstrated as high potential materials for niche applications such as three-dimensional cell culture, wound healing patches, and vitreous endotamponades. Recent developments saw the advent of thermogelling systems with advanced biomedical applications ranging from enhanced cancer therapy to radiology imaging to tissue engineering, and these are usually achieved by the conjugating of biologically relevant molecules such as drugs and peptides to the thermogel copolymer or by incorporating nanoparticles into the thermogel systems. New developments in this field see a shift away from employing traditional synthetic polymers such as polypropylene glycol (PPG) and poly(lactic-co-glycolic acid) (PLGA) to utilizing more advanced nature-derived bioactive molecules and also introducing chiral moieties in the thermogelling copolymer backbone.There are currently a few main types of thermogel copolymers such as diblock, triblock, end-capped, graft, and random multiblock polyurethane thermogels. Among these, our lab is specialized in the synthesis and application of polyurethane multiblock thermogels. These thermogels have the advantage of high molecular weights and enhanced intermolecular hydrogen bonding arising from the urethane groups. These generally allow for the formation of thermogelling systems with higher gel stiffness, resilience, and encapsulation efficiency, allowing these polyurethane thermogels to be well suited for niche applications such as sustained drug delivery and vitreous endotamponades. In this Account, we summarize the fundamental polymeric factors influencing the micellar and bulk polyurethane thermogel properties, provide our group’s insights into the rational design of these thermogels for various advanced applications and finally discuss the future possibilities of thermogelling systems. We speculate that there is still much untapped potential of thermogels in the biomedical field and these can possibly be achieved by designing thermogel copolymers with bioactive moieties and exploring more advanced branched architectures. In addition, we also propose the expansion of thermogels beyond biomedical fields, for which our lab has demonstrated thermogels as electrode contacts for noninvasive plant health monitoring.

Chiral Resolution of Spin-Crossover Active Iron(II) [2x2] Grid Complexes.

Chiral magnetic materials are proposed for applications in second‐order non‐linear optics, magneto‐chiral dichroism, among others. Recently, we have reported a set of tetra‐nuclear Fe(II) grid complex conformers with general formula C/S‐[Fe4L4]8+ (L: 2,6‐bis(6‐(pyrazol‐1‐yl)pyridin‐2‐yl)‐1,5‐dihydrobenzo[1,2‐d : 4,5‐d′]diimidazole). In the grid complexes, isomerism emerges from tautomerism and conformational isomerism of the ligand L, and the S‐type grid complex is chiral, which originates from different non‐centrosymmetric spatial organization of the trans type ligand around the Fe(II) center. However, the selective preparation of an enantiomerically pure grid complex in a controlled manner is difficult due to spontaneous self‐assembly. To achieve the pre‐synthesis programmable resolution of Fe(II) grid complexes, we designed and synthesized two novel intrinsically chiral ligands by appending chiral moieties to the parent ligand. The complexation of these chiral ligands with Fe(II) salt resulted in the formation of enantiomerically pure Fe(II) grid complexes, as unambiguously elucidated by CD and XRD studies. The enantiomeric complexes exhibited similar gradual and half‐complete thermal and photo‐induced SCO characteristics. The good agreement between the experimentally obtained and calculated CD spectra further supports the enantiomeric purity of the complexes and even the magnetic studies. The chiral resolution of Fe(II)‐ [2×2] grid complexes reported in this study, for the first time, might enable the fabrication of magneto‐chiral molecular devices.

In(III)-Catalyzed Direct Regioselective Syntheses of 1-Naphthaldehyde Derivatives via a Hidden Aldehyde 1,3-Translocation and Disjointed CO2 Extrusion

A highly regioselective annulation of 3-formylchromones with alkynes in the presence of indium triflate leads to the direct construction of diverse 1-naphthaldehyde derivatives. This one-pot de novo protocol features an unusual aldehyde 1,3-translocation and disjointed CO2 extrusion. This methodology is effective for the construction of structurally diverse 1-naphthaldehydes bearing chiral moieties and polyaromatics. These naphthaldehydes can be further easily elaborated into a wide variety of functional groups. Density functional theory computations show that this In(III)-catalyzed reaction appears to proceed via a stepwise dearomative cyclization, lactonization, ring contraction, and, finally, extrusion of CO2. Most interestingly, the aldehyde translocation occurs not by the transposition of the aldehyde but rather by the skeletal rearrangement of the substrate arene.

Strategies of In Situ Generated Magnesium Catalysis in Asymmetric Reactions

AbstractMagnesium (Mg) is a cheap, non-toxic, and recyclable alkaline earth metal that constitutes about 2% weight in the Earth’s crust. The use of magnesium catalysts to forge chiral moieties in molecules is highly attractive. Based on our work in recent years, we describe the current progress in the development of in situ generated magnesium catalysts and their application in asymmetric synthesis. In this perspective, a critically concise classification of in situ generated magnesium catalytic modes, with relevant examples, is presented, and representative mechanisms of each category are discussed. Building on the established diverse strategies, one can foresee that more innovative and structurally creative magnesium catalysts that are generated in situ will be developed to overcome more formidable challenges of catalytic enantioselective reactions.1 Introduction2 Magnesium Catalysts Generated in Situ from Chiral Ligands Containing Dual Reactive Hydrogens3 Magnesium Catalysts Generated in Situ from Monoanionic Chiral Ligands4 Bimetallic and Polymetallic Magnesium Catalysts Assembled in Situ5 Summary and Outlook

Self-Assembling Behavior and Chiroptical Properties of Carbazole-Cored Phenyl Isoxazolyl Benzenes.

Carbazole-cored phenyl isoxazolyl benzenes possessing chiral moieties were synthesized. The molecules self-assembled to form stacked supramolecular assemblies in an isodesmic fashion in chloroform, whereas the molecules preferably assembled in a cooperative fashion in methylcyclohexane (MCH), which was determined by spectroscopic methods, including UV-vis absorption, fluorescence, and 1H NMR spectroscopy. Clear nucleation and elongation processes were observed in the plot of the degree of aggregation (αagg) against temperature, which allowed us to determine the elongation temperature (Te), the enthalpic gain in the elongation process (ΔHe), the equilibrium constant between nucleation and elongation (Ka), and the degree of polymerization at the elongation temperature ([Nn(Te)]). Circular dichroism (CD) and circularly polarized luminescence (CPL) studies revealed the formation of helically stacked assemblies in solution. Moreover, the majority-rule effect was clearly observed in the solutions of mixtures of (S)- and (R)-1, indicating the chiral amplification behavior of the helically stacked assemblies consisting of (S)- and (R)-1. AFM provided morphological insight into the assemblies on mica, which clearly indicates the formation of polymeric assemblies in the solid state.

Ni(II) Schiff-Base Complexes as Chiral Electroauxiliaries and Methodological Platform for Stereoselective Electrochemical Functionalization of Amino Acids.

The concept of chiral electroauxiliary based on the redox active chiral platform to perform transformations of a redox inactive substrate is suggested and discussed in the context of the targeted stereoselective electrochemical functionalization of amino acids. Tailor-made amino acids are essential structural features of modern medicinal chemistry and drug design; the development of efficient synthetic approaches to these compounds is of topical interest. The modified substrate (an amino acid) is included as a structural motif in the redox active complex (with a possibility to be released after modification) that integrates "a bifunctional linker" (the structural motif capable to "catch" a substrate) and a chiral moiety responsible for asymmetry induction. The amino acid, being included as a part of such ensemble, becomes stable towards redox destruction and its targeted electrochemical modification saving the amino acid skeleton is possible, thus developing new modes of reactivity for well-known compounds.

Synthesis of chiral conjugated microporous polymer composite membrane and improvements in permeability and selectivity during enantioselective permeation

Three kinds of chiral conjugated microporous polymer composite membranes with porous silica as the support layer (CCMP/SiO2) were successfully prepared by surface-initiated Sonogashira-Hagihara polymerization for the first time. The skin layer thickness and morphology of the CCMP/SiO2 composite membrane were controlled by optimizing the concentration of monomers and solvents during polymerization. The obtained CCMP/SiO2 composite membranes showed high thermal stability and solvent stability. Racemates of phenylalanine (Phe) and tryptophan (Trp) were enantioselectively separated through CCMP/SiO2 composite membranes. The permeability and enantioselectivity were 2.07 × 10−5 m2/h and 94.1 %ee, respectively, for the (D,L)-Phe aqueous solution, and 1.17 × 10−5 m2/h and 84.9 %ee for (D,L)-Trp aqueous solution, respectively. The permeability of the CCMP/SiO2 composite membrane was more than 1000 times higher than that of the one-dimensional polymer chiral separation membrane when the selectivity was higher than 80 %ee. The excellent enantiomeric resolution performance of the CCMP/SiO2 composite membrane may be caused by the high content of micropores supported by the three-dimensional fully conjugated rigid framework and the presence of chiral moieties within the microporous polymers. As a result, highly enantioselective chiral conjugated microporous polymer composite membranes with extremely high permeability have been obtained.

Chiral derivatives of xanthones and benzophenones: Synthesis, enantioseparation, molecular docking, and tumor cell growth inhibition studies.

AbstractLiquid chromatography enantioseparation and determination of enantiomeric purity of synthetized xanthone and benzophenone derivatives comprising one or more chiral moieties are reported. High enantioselectivity and resolution were observed in (S,S)‐Whelk‐O1 chiral stationary phase (CSP) for the enantiomeric mixtures of compounds comprising an aromatic ring linked to the stereogenic center(s), with α values ranging from 1.35 to 4.15 and Rs values ranging from 2.22 to 13.87. Among all the tested enantiomeric mixtures, those comprising three chiral moieties positioned in the xanthone scaffold gave the best chromatographic results. Enantiomers comprising an alkyl chain linked to the stereogenic centers were enantioseparated on a Lux® Celullose‐2 CSP. For both CSPs, the elution was performed in polar organic mode. The enantiomeric ratio (e.r.) values were always higher than 99%. Additionally, assessment of chiral recognition mechanisms on (S,S)‐Whelk‐O1 CSP was performed by molecular docking approach, which are in accordance with the chromatographic parameters. The nature and number of chiral moieties in the central aromatic scaffold of either xanthone or benzophenone derivatives are proved to be crucial for enantiorecognition. The evaluation of the growth inhibition of human tumor cell lines revealed that (S,S)‐(+)‐5 was the most potent compound, with values of GI50 of 12.83 ± 2.09 μM for A375‐C5 melanoma, 12.40 ± 1.16 μM for MCF‐7 breast adenocarcinoma, and 13.06 ± 1.29 μM for NCI‐H460 non‐small cell lung cancer. In some cases, the growth inhibitory effects demonstrated to be dependent on the stereochemistry of the compounds.

Modulation of the optical properties of chiral porphyrin dimers by introducing bridged chiral amide-bonds

The d/l-enantiomers of a series of three Zn(II)tetraarylporphyrin dimers were synthesized and isolated by incorporating a bridging amide-bonded xanthene moiety at the para-position of one of the meso-aryl rings. The electronic structures and optical properties were modulated by incorporating chiral amino acid moieties into the amide-bonding moieties of the xanthene bridge that contain methyl, tolyl and 2-methylindole substituents. A cofacial dimer was formed in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) resulting in a significant red shift of the B band, due to a relative destabilization of the HOMO, which has large MO coefficients on the pyrrole nitrogens. The sign sequences observed in the B band region of the CD spectra due to the presence of the chiral amino acid moieties were modified due to this change in geometry. Significant CD intensity is also observed in the B band region of the CD spectra of anion radical species during in situ spectroelectrochemical measurements.

Dynamic Induction of Optical Activity in Triarylmethanols and Their Carbocations.

A series of artificial triarylmethanols has been synthesized and studied toward the possibility of exhibiting an induced optical activity. The observed chiroptical response of these compounds resulted from the chiral conformation of a triarylmethyl core. The chirality induction from a permanent chirality element to the liable triarylmethyl core proceeds as a cooperative and cascade process. The OH···O(R) and/or (H)O···HorthoC hydrogen bond formation along with the C–H···π interactions seem to be the most important factors that control efficiency of the chirality induction. The position of chiral and methoxy electron-donating groups within a trityl skeleton affects the amplitude of observed Cotton effects and stability of the trityl carbocations. In the neutral environment, the most intense Cotton effects are observed for ortho-substituted derivatives, which undergo a rapid decomposition associated with the complete decay of ECD signals upon acidification. From all of the in situ generated stable carbocations, only two exhibit intense Cotton effects in the low energy region at around 450 nm. The formation of carbocations is reversible; after alkalization, the ions return to the original neutral forms. Unlike most triarylmethyl derivatives known so far, in the crystal, the triarylmethanol, para-substituted with the chiral moiety, shows a propensity for a solid-state sorting phenomenon.

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

The introduction of chiral alkyl substituents into the lower rim of calix[4]arene immobilised in the 1,3-alternate conformation led to a system possessing a preorganised ureido cavity hemmed with chiral alkyl units in the near proximity. As shown by the 1H NMR titration experiments, these compounds can be used as receptors for chiral anions in DMSO-d6. The chiral recognition ability can be further strengthened by the introduction of another chiral moiety directly onto the urea N atoms. The systems with double chiral units being located around the binding ureido cavity showed better stereodiscrimination, with the highest selectivity factor being 3.33 (KL/KD) achieved for N-acetyl-ʟ-phenylalaninate. The structures of some receptors were confirmed by single crystal X-ray analysis.