Type Macrocycles Research Articles

Tetralactam macrocycle based aggregation-induced emission dots for selective detection of Fe3+ in water and drugs

Iron ion (Fe3+) is crucial for both biological organisms and the environment, and iron dyshomeostasis can lead to a variety of diseases and environmental issues. Therefore, the detection of Fe3+ is of significant importance across various fields. For this purpose, through the co-assembly of water-soluble tetralactam macrocycle H and 1,1,2,2-tetraphenylethylene (TPE), we prepared a new type of tetralactam macrocycle based aggregation-induced emission dots (AIE-dots), namely TPE@H. TPE@H exhibitted good water-solubility and allowed the water-insoluble TPE to aggregate and exhibit strong fluorescence emission in water. Furthermore, the fluorescence of TPE@H could be quenched by Fe3+ through the inner filter effect, making TPE@H a potential “turn-off” fluorescent probe for Fe3+ detection. TPE@H exhibited a limit of detection as low as 1 μM with high selectivity, and also retained good detection performance in domestic water, human serum, and even drugs, indicating its great potential for biological and environmental monitoring of Fe3+. This study not only provides a green and efficient method for detecting Fe3+, but also expands the approach for application of water-insoluble dyes in the aqueous environment.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling.

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

Phenothiazine Embedded Dithiasmaragdyrins.

Two different types of novel phenothiazine-embedded dithiasmaragdyrins containing one phenothiazine ring, two thiophene rings and two pyrrole rings connected via three meso carbons and two direct bonds in the macrocyclic framework were synthesized over the sequence of synthetic steps starting with phenothiazine. Three examples of phenothiazine-embedded dithiasmaragdyrins were synthesized by condensing appropriate phenothiazine-based pentapyrrane with pentafluorobenzaldehyde and two examples of phenothiazine sulfone embedded dithiasmaragdyrins were synthesized by condensing phenothiazine-based diol with appropriate meso-aryl dipyrromethane under mild acid-catalysed conditions. 1D&2D NMR studies revealed that the thiophene rings adopted inverted orientation in phenothiazine sulfone embedded dithiasmaragdyrins whereas in phenothiazine-embedded dithiasmaragdyrins, the thiophene rings were in normal orientation. Both types of macrocycles exhibit nonaromatic absorption features and showed panchochromic absorption features in its neutral and protonated forms. The electrochemical studies indicated that the phenothiazine-embedded dithiasmaragdyrins were more electron-rich compared to phenothiazine sulfone embedded dithiasmaragdyrins. DFT studies revealed that both types of dithiasmaragdyrins exhibit significantly distorted structures and TD-DFT studies support the experimental observations.

Experimental and theoretical study on the interaction of an ionic resorcin[4]arene and some pollutants in aqueous solution

The complexation process between an ionic resorcinarene, C-ethyl-tetraminomethylated-resorcin[4]arene hydrochloride, with resorcinol, phenol and potassium cyanide has been studied in aqueous solution using spectroscopic, calorimetric, and computational techniques. The results show the formation of resorcinarene-phenol and resorcinarene-resorcinol inclusion complexes stabilized by means of π-π interactions. On the other hand, the interaction between the macrocycle and the cyanide ions is principally mediated by ion pairing and electrostatic interactions. A turn-on effect on the fluorescence intensity is found when resorcinol or phenol is added to the macrocycle. The quantification and detection limits have been calculated and the obtained values are comparable to other sensors reported in the literature. These results extend the use of this type of macrocycles as chemosensors.

Absorption Spectra of Protonated Corroles: Two Distinct Patterns Due to Peripheral Substitution Architecture

The origin of individual features in the ground state absorption spectra of two protonated corroles differing in the architecture of peripheral substitution (either Cm-aryl or Cb-alkyl) have been studied in detail with the ground state absorption spectroscopy and density functional theory calculations. The geometry optimization, molecular orbitals and absorption spectra calculation have been carried out. It was found that protonation leads to the saddle type macrocycle conformation in contrast with the wave type conformation known for the parent-free base corroles. The mean plane deviation parameter Δ23 for the macrocycle, pyrrole tilting angles and the degree of pyramidalization λ2 of all four pyrrole nitrogens was found to depend on the peripheral substitution architecture. Macrocycle conformation of the protonated forms has distinct asymmetrical features which are reflected by the sets of values of the tilting angles and values of pyramidalization degree. The pair of pyrroles B and C has smaller tilting angles and higher pyramidalization degree values, whereas the opposite trend was found for the pair of pyrroles A and D. Electronic effects and structural differences induced by substitution lead to the pronounced shifts of the molecular orbitals. In the Cb-alkylated corrole, almost-degenerated HOMO and HOMO-1 molecular orbitals lead to enhancement of the configuration interaction. As a result, the Qx transition oscillator strength goes down, becoming comparable to that of the Qy one. A large HOMO-HUMO-1gap in the Cm-aryl corrole minimizes the configuration interaction, giving rise to Qx band domination in the visible range spectrum.

D-Idose-Based Monoaza-15-Crown-5 Lariat Ethers: Synthesis of an Elusive d-Hexose and Application of Derived Macrocycles in Enantioselective Syntheses

Carbohydrate-based macrocycles can be enantioselective catalysts in certain reactions. Previously, it was proven that the carbohydrate moiety could affect the catalytic activity of the monoaza-15-crown-5 type macrocycles derived from sugars. According to our experiments so far, the most effective enantioselective catalysts were the d-glucose- and the d-galactose-based crown ethers. To obtain more information about the effect of the carbohydrate unit, a rare monosaccharide, d-idose was incorporated into the monoaza-15-crown-5 structure. The key intermediates were methyl 4,6-O-benzylidene-α-d-idopyranoside and methyl 4,6-O-benzylidene-β-d-idopyranoside, which were synthesized from d-galactose. The efficiency of the idopyranoside-based crown compounds synthesized was investigated in asymmetric phase transfer reactions. In liquid-liquid biphasic reactions the highest enantioselectivity was 81% ee, while in solid-liquid phase systems the highest asymmetric induction was 67% ee. It was observed that the enantiodiscrimination was strongly dependent on the configuration of the anomeric center, on the side arm of the nitrogen, and on the structure of the substrate.

Calix[3]Pyrrole and Related Macrocycles: Synthesis and Properties

Calix[4]pyrrole is a porphyrinogen-like macrocycle in which four pyrrole units are linked by four sp3-hybridized carbon atoms at the α-positions. While such tetrapyrrolic macrocycles are readily synthesized by acid-catalyzed condensation reactions of pyrrole monomer and carbonyl compound, analogous macrocycles composed of three pyrrole units are always not observed. Calix[3]pyrrole is a ring-contracted analogue of calix[4]pyrrole, and has been missing in porphyrin-related chemistry. In this presentation, the first synthesis of calix[3]pyrrole and its furan-embedded analogues is reported, and their unique reactivity derived from their macrocyclic ring strain will be discussed.Synthesis of calix[3]pyrrole started with a linear trimer of 3,3-dimethylpentane-2,5-dione. Intramolecular cyclization of the linear hexaketone was accomplished in 5 steps to give a cyclic hexaketone precursor. Paal–Knorr type pyrrole formation reaction of cyclic hexaketone gave calix[3]pyrrole in 41% yield (Scheme 1). Using similar strategies, analogous calix[3]-type macrocycles, namely, calix[1]furan[2]pyrrole, calix[2]furan[1]pyrrole, and calix[3]furan, were successfully synthesized. Single crystal X-ray diffraction analysis of calix[3]pyrrole revealed its strained structure, and the theoretical calculations showed the strain energy of calix[3]pyrrole is 22.1 kcal/mol per unit higher than that of calix[4]pyrrole. Such strain energy tends to decrease as the number of pyrrole unit decreased.Calix[3]pyrrole exhibited unique reactivity derived from macrocyclic ring strain under acidic (Rothemund–Lindsey) conditions that are frequently used for porphyrin synthesis. When calix[3]pyrrole was dissolved in 10 mM solution of trifluoroacetic acid in dichloromethane, calix[6]pyrrole was quantitatively formed within 30 seconds (Scheme 1). Similar strain-induced ring expansion was observed for calix[1]furan[2]pyrrole, but full conversion took approximately 5 minutes. On the other hand, calix[2]furan[1]pyrrole and calix[3]furan did not show ring expansion. Detailed mechanistic analysis revealed that protonation at a pyrrole unit in calix[3]pyrrole triggers irreversible ring-cleavage to give a linear tripyrrane moiety which undergoes cyclodimerization under acidic conditions.The strain-induced ring expansion reaction of calix[3]pyrrole solved a long-standing question in porphyrin-related chemistry. Tripyrrolic macrocycles such as calix[3]pyrrole are, even formed, not isolable from pyrrole condensation reaction using acid, because the strain-induced conversion to calix[6]pyrrole is too fast. Besides, this reaction provided a novel approach to ring-expanded calix-type macrocycles. Figure 1

Effect of inclusion in sulfobutylether-β-cyclodextrin on the rate of merocyanine-spirobenzopyran reversible photochromic transformations

To gain insight into the effect of host-guest binding on the negative photochromic behavior, the reversible interconversion between a merocyanine dye and its spirobenzopyran (SP) isomer was studied in the cavity of sulfobutylether-β-cyclodextrin having on average 6.4 degrees of substitution (SBE6.4βCD). Depending on the acidity of the solution, trans-merocyanine (trans-MC) or its protonated form (trans-MCH+) were the thermodynamically most stable species both in water and in the interior of SBE6.4βCD. The association constant of 1:1 encapsulation significantly diminished in the series of SP > trans-MCH+ > trans-MC. Inclusion complex formation accelerated the visible-light-induced conversion to SP and efficiently slowed down the thermal back reaction in acidic and slightly basic medium alike. A good linear correlation was found between the logarithm of the frequency factors and the activation energies for the SP transformation to the colored most stable isomer within various types of macrocycles.

Host Dynamics under General-Purpose Force Fields.

Macrocyclic hosts as prototypical receptors to gaseous and drug-like guests are crucial components in pharmaceutical research. The external guests are often coordinated at the center of these macromolecular containers. The formation of host-guest coordination is accompanied by the broken of host-water and host-ion interactions and sometimes also involves some conformational rearrangements of the host. A balanced description of various components of interacting terms is indispensable. However, up to now, the modeling community still lacks a general yet detailed understanding of commonly employed general-purpose force fields and the host dynamics produced by these popular selections. To fill this critical gap, in this paper, we profile the energetics and dynamics of four types of popular macrocycles, including cucurbiturils, pillararenes, cyclodextrins, and octa acids. The presented investigations of force field definitions, refitting, and evaluations are unprecedently detailed. Based on the valuable observations and insightful explanations, we finally summarize some general guidelines on force field parametrization and selection in host-guest modeling.

Studi Difusi Gadolinium Makrosiklik Pada Sel Kupffer Menggunakan Simulasi Monte Carlo Cell

Contrast agents containing gadolinium (Gd) are classified into two types based on their molecular structure: linear and macrocyclic. The macrocyclic type is known for its enhanced stability, resulting in minimal release of Gd ions within the body. The distribution of macrocyclic Gd within the kupffer cells in the liver, undergoes a diffusion process. In this study aimed to investigate the diffusion mechanism of macrocyclic gadolinium in kupffer cells. It employs a simulation geometry model employing Monte Carlo Cell and a three-compartment experimental model. The kupffer cell model in the simulation was generated using Blender 2.93 application, consisting of three compartments, while the experimental model involved three compartments containing a NaCl solution. The simulation results revealed that kupffer cell membran densities of 1480 molekul/μm2, 2961 molekul/μm2, 4442 molekul/μm2, and 5922 molekul/μm2 exhibited respective half-lifes of 0.547 s, 0.261 s, 0.198 s, and 0.148 s. Furthermore, the experimental results indicated that the models with 100, 200, 300, and 400 holes displayed half-lives of 1720 s, 578 s, 530 s, and 240 s, respectively. Result this research shows that higher membrane density and more significant number of holes results in faster molecule diffusion.

Toward calix[2]-type macrocycles: Synthesis and structural analysis of cyclic tetraketone and highly strained furanophane

Recent progress in the synthesis of calix[3]pyrrole has proven that cyclic polyketones composed of 3,3-dialkylated pentane-2,4-diones as the repeating unit are promising precursors for strained calix-type macrocycles. Toward the synthesis of calix[2]pyrrole and calix[2]furan, which are the most strained congeners among the possible calix[[Formula: see text]]pyrroles and calix[[Formula: see text]]furans, we report the synthesis of a cyclic dimer of 3,3-dimethylpentane-2,4-dione and its furanophane derivative. These compounds were produced from a linear tetraketone precursor. Single crystal X-ray diffraction analysis revealed that the furan ring in the furanophane was highly strained with deformation angles [Formula: see text] and [Formula: see text] of 3.69[Formula: see text] and 16.00[Formula: see text], respectively. These deformation angles were the largest in the series of 1,4-diketone-linked oligofuran macrocycles. Although these two macrocyclic compounds are likely the most promising precursors for calix[2]-type macrocycles, Paal–Knorr-type pyrrole or furan ring formation did not proceed under standard conditions used for calix[3]pyrrole or calix[3]furan. Theoretical calculations indicated that the second aromatic ring formation on the cyclic tetraketone is a highly uphill process whose activation energy cannot be overcome by standard thermal reactions.

Absorption spectra of calix[3]pyrrole analogs as probes for contracted macrocycles

Calix[3]pyrrole and its furan derivatives exhibited bathochromically shifted lowest-energy electronic transition bands in their absorption spectra compared with their calix[4]- and calix[6]-pyrrole analogues, despite the repeating units being the same. We also observed fluorescence emission for calix[3]-type macrocycles. The Stokes shift of the furan/pyrrole hybrid macrocycles, calix[2]furan[1]-pyrrole, and calix[1]furan[2]pyrrole, substantially varied depending on the solvent polarity. Non-covalent interaction (NCI) analyses indicated enhanced interactions between neighboring aromatic rings in the calix[3]pyrrole macrocycle, whereas such interactions were weak in calix[4]pyrrole, in which the interchromophore distance is remarkably longer than in calix[3]pyrrole. Theoretical analyses indicated that the red-shifted, lowest-energy bands of calix[3]pyrrole correspond to HOMO–LUMO transitions, the energy gap of which was narrow compared with calix[4]pyrroles. The characteristic absorption bands for calix[3]pyrrole and its related macrocycles are useful as probes for distinguishing such macrocycles from higher calix[[Formula: see text]]pyrrole ([Formula: see text] 4) analogues that exhibit almost identical absorption spectra.

N-protected pyrroles as synthons for variants of coremodified N-confused calixphyrins: Spectroscopic and theoretical characterization

A new convergent synthetic methodology has been adopted for syntheses of two hitherto unknown new generation of core-modified N-confused calixphyrins and an all four meso-sp3 centered heterocyclic macrocycle with [Formula: see text],[Formula: see text]-pyrrole connectivities via acid catalyzed Lindsey type condensation of thiophene diol with N-protected pyrrole(s) using BF3.Et2O followed by oxidation with chloranil. All of the macrocycles have been achieved in moderately good yields. Their structures, electronic and optical properties have been elucidated by NMR, UV-Vis-NIR spectroscopic analyses and in-depth theoretical calculations. The type of macrocycles are a mere consequence of the type of N-protected pyrroles used as synthons with the UV-Vis spectra closely resembling the spectra for calixphyrins. Detailed structural analyses using 1H-1H (COSY, ROESY), 13C-1H (HSQC) 2D NMR studies and DFT level theoretical investigations indicated lack of macrocyclic [Formula: see text] conjugation with [Formula: see text],[Formula: see text] and/or [Formula: see text],[Formula: see text] pyrrole connectivities.

The synthesis and near-infrared photothermal conversion of organometallic interdigitated complex and “U” type macrocycles

Herein, one interdigitated molecular and two metallarectangles were realized successfully using two rigid bidentate ligands (L1, L2) and two building blocks (E1, E2) via coordination-driven self-assembly strategy. Interestingly, a novel interdigitated structure has been successfully formed through triple π-π stacking interactions, different from the previously reported interlocked [2]catenanes. Based on the π-π stacking interaction, nonradiative transitions were promoted and obvious photothermal transitions effect was triggered in solution and solid states. In addition, it is found that the interdigitated structure has a decent photothermal conversion efficiency of about 12% in solution state. This study provides open up new ideas for our future development of near-infrared photothermal conversion materials.

Selective union of ATP vs ADP to an amino/amide macrocycle and its Cu2+ complexes: potentiometric, spectrophotometric and theoretical approximations

The protonation equilibria of a new amine/amide type macrocycle and its complexation with Cu(II) in solution have been studied by potentiometry and UV-Visible Spectrophotometry. The ligand shows four protonation constants and one unusual deprotonation constant. Six mononuclear and four binuclear copper II complexes were found and reported its stability constant values. Some species predominate in specific ranges of pH, which might be important for biomimetic studies. It was found that the studied ligand forms stable mononuclear and binuclear complexes with Cu (II) and these species have similar geometries, squared pyramid, above pH 7. An evaluation through its potentiometrically determined stability constants of the selective recognition of ATP over ADP by this macrocycle and its Cu (II) complexes is presented. With or without the presence of Cu (II) ions, the ligand forms more stable complexes with ATP over ADP, the stability of these species increase with pH. Both, the stability quotients and the species distribution diagrams for the ATP-ADP mixed systems shows the inclination of the studied systems to selectively bind ATP over ADP, so, in principle, they can be used for the selective recognition of ATP or as catalysts in the hydrolysis of this nucleotide.

Chemistry of tellurium containing macrocycles

Abstract The chemistry of Tellurium containing macrocycles has received great attraction and developed rapidly. Recently inorganic chemists are fascinated by ligands containing macrocycles having tellurium as soft donor and N and O as hard donor atoms. The tellurium atom is more electropositive than carbon due to its large size that resulted in polarisation of Te–C bond. So, tellurium containing macrocycles are explored due to their high reactivity and toxicity. Well-designed macrocycles containing different metals is an interesting field of chemistry as macrocycle with mixed donor atoms can bind two different metal atoms with different nature within the same cavity and thereby ion selectivity increases. Chemistry of macrocycles with tellurium as soft donor atoms also gives rise to very interesting coordination behaviour as addition of Tellurium in macrocycle adds an additional probe (125Te NMR help to monitor their structures in solutions). The chemistry of hard and soft donors in macrocyclic framework makes interesting coordination chemistry and need to be explore. The discussion includes different types of tellurium macrocycles and their chemistry.

Pyrrole bearing diazocrowns: Selective chromoionophores for lead(II) optical sensing

Diazocrowns of 18-, 21- and 23-membered rings with pyrrole residue as a part of macrocycle were for the first time used as chromoionophores in lead(II) selective optodes. Sensing properties of optodes depend on the type of macrocycle, namely its size and the type of linker: oligoether or hydrocarbon chain. The best results were obtained for optode bearing 18-membered crown with oligoether linker showing linear response range of 8.05 × 10−8–2.24 × 10−5 M lead(II) and detection limit of 1.15 × 10−8 M. Membrane, based on cellulose triacetate, is lead(II) selective giving color change from red to different shades of blue (pH 5.5). Results obtained for model and real samples of lead(II) showed that easily accessible and regenerable sensor material can be used for spectrophotometric and colorimetric (Digital Color Analysis) detection and determination of lead(II).

Strain-Induced Ring Expansion Reactions of Calix[3]pyrrole-Related Macrocycles.

The recent discovery of calix[3]pyrrole, a porphyrinogen-like tripyrrolic macrocycle, has provided an unprecedented strain-induced ring expansion reaction into calix[6]pyrrole. Here, we synthesized calix[n]furan[3-n]pyrrole (n=1∼3) macrocycles to investigate the reaction scope and mechanism of the ring expansion. Single crystal X-ray analysis and theoretical calculations revealed that macrocyclic ring strain increases as the number of inner NH sites increases. While calix[1]furan[2]pyrrole exhibited almost quantitative conversion into calix[2]furan[4]pyrrole within 5 minutes, less-strained calix[2]furan[1]pyrrole and calix[3]furan were inert. However, N-methylation of calix[2]furan[1]pyrrole induced a ring-expansion reaction that enabled the isolation of a linear reaction intermediate. The mechanism analysis revealed that the ring expansion consists of regioselective ring cleavage and subsequent cyclodimerization. This reaction was further utilized for synthesis of calix[6]-type macrocycles.

Air-Stable Dy(III)-Macrocycle Enantiomers: From Chiral to Polar Space Group

Air-Stable Dy(III)-Macrocycle Enantiomers: From Chiral to Polar Space Group

Strontium Hydride Cations Supported by a Large NNNNN Type Macrocycle: Synthesis, Structure, and Hydrofunctionalization Catalysis.

The use of the 15-membered NNNNN macrocyclic ligand Me5PACP (Me5PACP = 1,4,7,10,13-pentamethyl-1,4,7,10,13-pentaazacyclopentadecane) allowed the isolation of two cationic strontium hydride complexes by hydrogenolysis of benzyl precursors. Treatment of sparingly soluble [(Me5PACP)Sr(CH2Ph)2] with dihydrogen gave free Me5PACP, toluene, and oligomeric strontium hydride [SrH2]n, while hydrogenolysis in the presence of 1 equiv of the benzyl cation [(Me5PACP)Sr(CH2Ph)][B(C6H3-3,5-Me2)4] enabled isolation of the thermally unstable trihydride cation [(Me5PACP)2Sr2(μ-H)3][B(C6H3-3,5-Me2)4]. When the benzyl cation [(Me5PACP)Sr(CH2Ph)][BAr4]2 (Ar = C6H3-3,5-Me2 or C6H4-4-nBu) was reacted with dihydrogen or n-octylsilane, dihydride complexes [(Me5PACP)2Sr2(μ-H)2][BAr4]2 containing a dinuclear core bridged by two hydride ligands were obtained. The soluble dihydride complex [(Me5PACP)2Sr2(μ-H)2][B(C6H4-4-nBu)4]2 was tested in olefin hydrogenation and hydrosilylation catalysis. Kinetic analyses for [(Me5PACP)2Sr2(μ-H)2]2+ showed lower catalytic activity as compared to that of the isostructural calcium homologue [(Me5PACP)2Ca2(μ-H)2]2+. This is explained by a shift in the monomer-dimer equilibrium which precedes the catalytic cycle.