Macrocyclic Structure Research Articles

Pyrrocidine A, a metabolite of endophytic fungi, has a potent apoptosis-inducing activity against HL60 cells through caspase activation via the Michael addition.

Pyrrocidine A is a known antimicrobial compound produced by endophytic fungi and has a unique 13-membered macrocyclic alkaloid structure with an α,β-unsaturated carbonyl group. We have previously reported that pyrrocidine A shows potent cytotoxicity against human acute promyelocytic leukemia HL60 cells, and the activity is 70-fold higher than that of pyrrocidine B which is the analog lacking the α,β-unsaturated carbonyl group. Pyrrocidine A induced nuclear condensation, DNA fragmentation and caspase activation in HL60 cells. Since the DNA fragmentation was suppressed by pretreatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-fmk), caspase-mediated apoptosis contributes to pyrrocidine A-induced cytotoxicity. JFCR39 human cancer cells panel indicated that the mechanism of action of pyrrocidine A is different from other clinical anticancer drugs, and this compound broadly inhibited the growth of various cancer cell lines. The apoptosis induction by pyrrocidine A was suppressed by both N-acetyl-l-cysteine (NAC) and glutathione, both of which are thiol-containing antioxidants. Furthermore, pyrrocidine A directly bound to N-acetyl-l-cysteine methyl ester (NACM) through the Michael-type addition at the α,β-unsaturated carbonyl group and was detected by HPLC and liquid chromatography-ESI-tandem MS (LC-ESI-MS/MS) analyses. This indicates that this moiety is crucial for the potent apoptosis-inducing activity of pyrrocidine A.

Photoinduced processes in macrocyclic isoalloxazine–anthracene systems

Abstract Two new macrocyclic structures containing 8-hidroxyisoalloxazine and 1,5-dihydroxyanthracene moieties linked by aliphatic chains of different lengths ( n = 4 and 6) were designed and synthesized in order to study photoinduced electron transfer (PET) processes from the anthracene unit towards the isoalloxazine singlet excited state induced by structural changes due to different intrachromophoric distances and orientations. The compounds have been fully characterized by NMR spectroscopy and the X-ray solid state structures of both macrocycles have been elucidated. Photophysical measurements, including continuous wavelength photoinduced absorption (cw-PIA), at room temperature and 77 K have been carried out in order to investigate the influence of the close contacts between the aromatic groups (π–π stacking) on the photophysical properties of the macrocycles.

Photocatalytic oxidation desulfurization of model diesel over phthalocyanine/La0.8Ce0.2NiO3

A series highly efficient and stable metallophthalocyanine/La0.8Ce0.2NiO3 (ML/LCNO) photocatalysts were prepared by a facile sol–gel and immersion method. The as-prepared samples were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), TEM, N2 adsorption–desorption, and UV–Vis. The results revealed that LCNO calcined at 700°C possessed a perovskite structure with porous, and phthalocyanine not only adsorbed on the surface but also loaded in the pores of the LCNO oxide. The photocatalytic activities of the samples were evaluated by the photocatalytic oxidation of dibenzothiophene (DBT) under simulated sunlight irradiation. It was found that either macrocyclic structure or center metal of phthalocyanine had great influences on the photocatalytic activity of ML/LCNO. The oxidative reactivity of the different macrocycles was found in the order of MPc/LCNO>MTAP/LCNO>MPTpz/LCNO; which of different center metals was CoL/LCNO>FeL/LCNO>MnL/LCNO>NiL/LCNO>CuL/LCNO. The catalysts were reused several times with a slight decrease in activity. Furthermore, this kinetics of photocatalytic oxidation of DBT indicated that the reaction was a pseudo-first-order reaction.

Porphyrin-Metalation-Mediated Tuning of Photoredox Catalytic Properties in Metal–Organic Frameworks

Photoredox catalytic activation of organic molecules via single-electron transfer processes has proven to be a mild and efficient synthetic methodology. However, the heavy reliance on expensive ruthenium and iridium complexes limits their applications for scale-up synthesis. To this end, photoactive metal–organic frameworks (MOFs) exhibit unique advantages as novel heterogeneous photocatalytic systems, yet their utilization toward organic transformations has been limited. Here we describe the preparation and synthetic applications of four isostructural porphyrinic MOFs, namely, UNLPF-10a, -10b, -11, and -12, which are composed of free base, InIII-, SnIVCl2-, and SnIV-porphyrin building blocks, respectively. We demonstrate that the metalation with high valent metal cations (InIII and SnIV) significantly modifies the electronic structure of porphyrin macrocycle and provides a highly oxidative photoexcited state that can undergo efficient reductive quenching processes to facilitate organic reactions. In part...

Syntheses and Structures of Thiophene-Containing Cycloparaphenylenes and Related Carbon Nanohoops

Thiophene-containing cycloparaphenylenes (CPPs) bearing 8, 10, and 16 aromatic and heteroaromatic units in the macrocyclic ring structures were synthesized. Specifically, two and four thiophene-2,5-diyl units were incorporated into functionalized [6]- and [12]CPP macrocyclic carbon frameworks, respectively. In addition, two 2,2'-bithiophene-5,5'-diyl units were inserted into a functionalized [6]CPP carbon framework. The cyclic and differential pulse voltammetry and the UV-vis and fluorescence spectra of the fully aromatized macrocycles and their precursors exhibited interesting electrochemical and optical properties.

Macromolecular Crystallography for Synthetic Abiological Molecules: Combining xMDFF and PHENIX for Structure Determination of Cyanostar Macrocycles.

Crystal structure determination has long provided insight into structure and bonding of small molecules. When those same small molecules are designed to come together in multimolecular assemblies, such as in coordination cages, supramolecular architectures and organic-based frameworks, their crystallographic characteristics closely resemble biological macromolecules. This resemblance suggests that biomacromolecular refinement approaches be used for structure determination of abiological molecular complexes that arise in an aggregate state. Following this suggestion we investigated the crystal structure of a pentagonal macrocycle, cyanostar, by means of biological structure analysis methods and compared results to traditional small molecule methods. Cyanostar presents difficulties seen in supramolecular crystallography including whole molecule disorder and highly flexible solvent molecules sitting in macrocyclic and intermolecule void spaces. We used the force-field assisted refinement method, molecular dynamics flexible fitting algorithm for X-ray crystallography (xMDFF), along with tools from the macromolecular structure determination suite PHENIX. We found that a standard implementation of PHENIX, namely one without xMDFF, either fails to produce a solution by molecular replacement alone or produces an inaccurate structure when using generic geometry restraints, even at a very high diffraction data resolution of 0.84 Å. The problems disappear when taking advantage of xMDFF, which applies an optimized force field to realign molecular models during phasing by providing accurate restraints. The structure determination for this model system shows excellent agreement with the small-molecule methods. Therefore, the joint xMDFF-PHENIX refinement protocol provides a new strategy that uses macromolecule methods for structure determination of small molecules and their assemblies.

Macrocyclic Oligoesters Incorporating a Cyclotetrasiloxane Ring.

Macrocyclic oligoester structures based on a cyclotetrasiloxane core consisting of tricyclic (60+ atoms) and pentacycylic (130+ atoms) species were identified as the major components of a lipase-mediated transesterification reaction. Moderately hydrophobic solvents with log P values in the range of 2-3 were more suitable than those at lower or higher log P values. Temperature had little effect on total conversion and yield of the oligoester macrocycles, except when a reaction temperature of 100 °C was employed. At this temperature, the amount of the smaller macrocycle was greatly increased, but at the expense of the larger oligoester. For immobilized lipase B from Candida antarctica (N435), longer chain length esters and diols were more conducive to the synthesis of the macrocycles. Langmuir isotherms indicated that monolayers subjected to multiple compression/expansion cycles exhibited a reversible collapse mechanism different from that expected for linear polysiloxanes.

Antimicrobial Photosensitizers: Drug Discovery Under the Spotlight.

Although photodynamic therapy (PDT) was discovered over a hundred years ago by its ability to destroy microorganisms, it has been developed mainly as a cancer therapy. In recent years, due to the inexorable rise in multi-antibiotic resistant strains of pathogens, PDT is being considered as a versatile antimicrobial approach to which microbial cells will not be able to develop resistance. The goal of this review is to survey the different classes of chemical compounds that have been tested as antimicrobial photosensitizers. Some of these compounds have been known for many years, while others have been rationally designed based on recently discovered structural principles. Tetrapyrrole-based compounds (some of which are approved as cancer therapies) that efficiently generate singlet oxygen are more efficient and broad-spectrum when they bear cationic charges, As the macrocycle structure moves from porphyrins to chlorins to phthalocyanines to bacteriochlorins the long wavelength absorption moves to the near-infrared where tissue penetration is better. Four main types of natural products have been tested: curcumin, riboflavin, hypericin and psoralens. Phenothiazinium dyes, such as methylene blue and toluidine blue, have been tested, and some are clinically approved. A variety of non-phenothiazinium dyes with xanthene, triarylmethane and indocyanine structures have also been tested. New ring structures based on BODIPY, squaraine and fullerene cages can also mediate antimicrobial PDT. Finally the process of photocatalysis using titanium dioxide can also have medical uses. Designing new antimicrobial photosensitizers is likely to keep chemists engaged for a long time to come.

A General Approach to Sequence-Controlled Polymers Using Macrocyclic Ring Opening Metathesis Polymerization.

A new and general strategy for the synthesis of sequence-defined polymers is described that employs relay metathesis to promote the ring opening polymerization of unstrained macrocyclic structures. Central to this approach is the development of a small molecule “polymerization trigger” which when coupled with a diverse range of sequence-defined units allows for the controlled, directional synthesis of sequence controlled polymers.

Radical Polymerization of methacrylates with an adamantane-like rigid core derived from naturally occurringmyo-inositol

Trimethacrylate and dimethacrylate with rigid adamantane-like cores were synthesized from myo-inositol orthoester, and their radical homopolymerization and copolymerization with methyl methacrylate (MMA) were investigated. The radical homopolymerization of trimethacrylate yielded a networked polymer with higher thermal stability than that of a networked polymer synthesized by radical homopolymerization of 1,3,5-cyclohexanetriol-derived trimethacrylate, demonstrating the effect of adamantane-like core rigidity on the increase in thermal stability. Further, dimethacrylate underwent cyclopolymerization, forming a macrocyclic structure in the repeating unit, as the two methacrylate groups were oriented axially from the rigid orthoester-core and thus located close to each other. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2411–2420

Crystalline Bis-urea Nanochannel Architectures Tailored for Single-File Diffusion Studies

Urea is a versatile building block that can be modified to self-assemble into a multitude of structures. One-dimensional nanochannels with zigzag architecture and cross-sectional dimensions of only ∼3.7 Å × 4.8 Å are formed by the columnar assembly of phenyl ether bis-urea macrocycles. Nanochannels formed by phenylethynylene bis-urea macrocycles have a round cross-section with a diameter of ∼9.0 Å. This work compares the Xe atom packing and diffusion inside the crystalline channels of these two bis-ureas using hyperpolarized Xe-129 NMR. The elliptical channel structure of the phenyl ether bis-urea macrocycle produces a Xe-129 powder pattern line shape characteristic of an asymmetric chemical shift tensor with shifts extending to well over 300 ppm with respect to the bulk gas, reflecting extreme confinement of the Xe atom. The wider channels formed by phenylethynylene bis-urea, in contrast, present an isotropic dynamically average electronic environment. Completely different diffusion dynamics are revealed in the two bis-ureas using hyperpolarized spin-tracer exchange NMR. Thus, a simple replacement of phenyl ether with phenylethynylene as the rigid linker unit results in a transition from single-file to Fickian diffusion dynamics. Self-assembled bis-urea macrocycles are found to be highly suitable materials for fundamental molecular transport studies on micrometer length scales.

Construction of Identical [2 + 2] Schiff-Base Macrocyclic Ligands by LnIII and ZnII Template Ions Including Efficient YbIII Near-Infrared Sensitizers

Identical 34-membered [2 + 2] pendent-armed Schiff-base macrocyclic ligands (H4La and H4Lb) can be constructed via the condensation reactions between rigid o-phenylenediamine and extended dialdehydes (H2hpdd/H2pdd) in the presence of either Ln(III) or Zn(II) template with remarkable distinction on the ion radii and charge. X-ray single-crystal diffraction analyses reveal the formation of mononuclear Ln(III) complexes (1-4 and 7) and dinuclear Zn(II) complexes (5 and 6). It is noted that Ln(III) macrocyclic complexes have eight-coordinate sandwich-like mononuclear structures fully surrounded by flexible and large-sized macrocyclic ligands. Photophysical studies have demonstrated that both H4La and H4Lb can serve as effective sensitizers for the Yb(III) ion (2 and 7) exhibiting near-infrared emission at 974 nm with high quantum yields in solution (C2H5OH and CH3OH, ∼1%). Moreover, the quantum yields of two Yb(III) complexes 2 and 7 could be increased ∼15% in CH3OH under weak alkaline condition (pH = 8-9), while no significant changes are observed in C2H5OH by contrast. We think the unique sandwich-like macrocyclic structures of Yb(III) complexes 2 and 7 play important roles in simultaneously guaranteeing the effective match of the energy levels of Yb(III) centers as well as shielding from the solvent molecules and counterions.

The Relationship Between Carbon Nanotube Surface Status and Electrocatalytic Performance Toward Oxygen Reduction Reaction of Cobalt Phthalocyanine /Carbon Nanotube

Recently, noble metals and their alloys nanoparticles supported on the carbon materials as carbon-based composite electrocatalysts are widely studied. However, on one hand, the high cost associated to these noble metals is still a drawback for full commercial application; on the other hand, their designing is limited by their characteristic. It is important to develop a new catalyst with low cost, high catalytic activity and wide designing for oxygen reduction reaction. Cobalt Phthalocyanine (CoPc) has high catalytic activity, and its special macrocyclic structure can perform well with the carbon materials toward Oxygen Reduction Reaction (ORR). Thus, the design of relationship between CoPc and its carbon-base is a necessary mission for this new catalyst for ORR. This abstract mainly focused on the different surface treatment of carbon nanotubes (CNTs) connect to CoPc and their electrocatalytic performance for the ORR process. Investigating raw CNTs, acidification CNTs (AF-CNTs) and activation CNTs gives us three different surface treatment CNTs coated by CoPc, which have higher electrocatalytic performance than CoPc itself. Here we find CoPc /AF-CNTs exhibit highest catalytic activity, and the Tafel Polarization curve test showed that CoPc/AF-MWCNTs perform the highest exchange current density (i0) in oxygen reduction reaction, and even its reaction rate is faster than commercial catalyst. The results indicated that the broken CNTs surface is beneficial for coating CoPc, as well as the charge transformation during the catalytic process. At the same time oxygen- containing groups on carbon-base can promote catalytic activity of CoPc for the ORR process. Figure 1

Synthesis and characterization of macrocyclic and polymeric Schiff base complexes derived from related macrocyclic ligands in the presence of Ni(II) and Cu(II)

Four macrocyclic Schiff base ligands (L1, L2, L3, and L4) have been prepared. In the presence of Copper(II), original macrocycles were converted to the three new binuclear polymeric complexes [Cu2L 2 1′ ](NO3)2, [Cu2L 2 2′ ](NO3), and [Cu2L 2 3′ ](NO3)2. But in the presence of Nickel(II), macrocyclic rings remained unchanged and Schiff base complexes of [NiL1(CH3CN)2(CH3OH)2](ClO4)2 and [NiL4](NO3)2 were synthesized. All ligands and their related complexes were characterized by elemental analysis, IR spectroscopy, in the case of ligands 1H, 13C NMR and EI-Mass and for [Cu2L2′](NO3)2 and [NiL1(CH3CN)2(CH3OH)2](ClO4)2 complexes X-ray crystal structure determination have been performed. Crystal structure showed 1D zigzag polymer for [Cu2L 2 1′ ](NO3)2 and macrocyclic structure for [NiL1(CH3CN)2(CH3OH)2](ClO4)2 complexes. The ligands and related polymeric complexes were screened for their antibacterial activities against six bacterial strains and the complexes showed antibacterial effects.

ChemInform Abstract: Supramolecular Control of Transition Metal Complexes in Water by a Hydrophobic Cavity: A Bio‐Inspired Strategy

AbstractReview: [67 refs.

Macrocyclic naphthalene diimides as G-quadruplex binders

The synthesis, biological and molecular modeling evaluation of a series of macrocyclic naphthalene diimides is reported. The present investigation expands on the study of structure–activity relationships of prototype compound 2 by constraining the molecule into a macrocyclic structure with the aim of improving its G-quadruplex binding activity and selectivity. The new derivatives, compounds 4–7 carry spermidine- and spermine-like linkers while in compound 8 the inner basic nitrogen atoms of spermine have been replaced with oxygen atoms. The design strategy has led to potent compounds stabilizing both human telomeric (F21T) and c-KIT2 quadruplex sequences, and high selectivity for quadruplex in comparison to duplex DNA. Antiproliferative effects of the new derivatives 4–8 have been evaluated in a panel of cancer cell lines and all the tested compounds showed activity in the low micromolar or sub-micromolar range of concentrations. In order to rationalize the molecular basis of the DNA G-quadruplex versus duplex recognition preference, docking and molecular dynamics studies have been performed. The computational results support the observation that the main driving force in the recognition is due to electrostatic factors.

ChemInform Abstract: Evaluation of Structural Effects of Acyclic and Macrocyclic Ligands Derived from (R,R)‐Cyclohexane‐1,2‐diamine in the Enantioselective Cu(II)‐Catalyzed Henry Reaction.

AbstractTwo new ligands with acyclic and macrocyclic structure are synthesized and tested in the Henry reaction of benzaldehyde with nitromethane.

Molecular and crystal structure of 2,11,14,17,20,23-hexaoxa-1,12(16,4α)-di-(19-nor-ent-beyerane)tetracosaphane-3,10,13,24-tetraone

The molecular and crystal structure of 2,11,14,17,20,23-hexaoxa-1,12(16,4α)-di-(19-nor-ent-beyerane)tetracosaphane-3,10,13,24-tetraone was determined by X-ray diffraction. This compound has a macrocyclic structure consisting of two molecules of the diterpenoid dihydroisosteviol (16-hydroxy-ent-beyeran-19-oic acid), which are linked by triethylene glycol and hexamethylene spacers. The compound crystallizes in the space group P21 with one independent molecule per asymmetric unit.

Macrospirocyclic oligomer based on triphenylamine and diphenylphosphine oxide as a bipolar host for efficient blue electrophosphorescent organic light-emitting diodes (OLEDs).

A novel bipolar oligomer (TPA-PO)3 was prepared as a host material for efficient blue phosphorescent organic light-emitting diodes (OLEDs). Through the C-9s of the fluorene units, three triphenylamine units attached to diphenylphosphine oxide are connected in series to form a macrocyclic structure. The solution-processed phosphorescent device based on FIrpic and (TPA-PO)3 achieved a maximum current efficiency of 19.4 cd A(-1) and a maximum luminance of 11,500 cd m(-2) with a relatively low efficiency roll-off.

Tuning the Supramolecular Structure through Variation of the Ligand Geometry and Metal Substituents–Diorganotin Macrocycles and Coordination Polymers Derived from cis- and trans-1,2-, 1,3-, and 1,4-Cyclohexanedicarboxylic and cis,cis-1,3,5-Cyclohexanetricarboxylic Acid

cis- and trans-1,2-chdcaH2, 1,3-chdcaH2, and 1,4-chdcaH2 (chdcaH2 = cyclohexanedicarboxylic acid) as well as cis,cis-1,3,5-chtcaH3 (chtcaH3 = cyclohexanetricarboxylic acid) have been treated with dimethyl- and di-n-butyltin reagents, and for the case of 1,4-chdcaH2 additionally with di-tert-butyltin dichloride, to determine whether macrocyclic or polymeric diorganotin dicarboxylates are formed dependent of the spatial orientation of the coordinating ligand functions and the organic substituents at the metal atom and to analyze conformational and topological variations in the resulting supramolecular aggregates. The single-crystal X-ray diffraction studies showed that besides the ligand geometry the substituents at the metal center are key elements for the formation of either monomeric, cyclo-oligomeric, or polymeric assemblies. Two of the compounds characterized by X-ray diffraction analysis exhibited macrocyclic ring structures, [{Me2Sn(cis-e,a-1,4-chdca)}2] and [{nBu2Sn(cis-e,a-1,4-chdca)}4]. For most o...