Macrocyclic Complexes Research Articles

Biologically important 26-32-membered macrocyclic complexes of manganese (II): In situ one pot template synthesis (IOPTS), characterization and bio-efficacy

Twenty six to thirty two membered tetraazamacrocyclic complexes of manganese (II) have been synthesized by template condensation of MnCl2.4H2O with dicarboxylic acid (malonic, succinic, glutaric or adipic acid) and 1,8-diaminooctane in 1:2:2 molar ratios. The new products with octahedral geometry have been characterized by elemental analyses, molecular weight determinations, molar conductance, magnetic moment and spectral studies viz., infrared and electronic. On the basis of the spectral studies the binding sites are proposed as the nitrogen atom of the macrocycles. The formulation of the complexes as [Mn(Macn)Cl2] (where n = 1 - 4) has been established on the basis of chemical composition. To assess the growth inhibiting potential of the manganese (II) complexes biological screening has been undertaken.

Surface bonding of MN4 macrocyclic metal complexes with pyridine-functionalized multi-walled carbon nanotubes for non-aqueous Li-O2 batteries

It is essential to develop bifunctional catalysts with high activity and stability for reversible oxygen reduction reactions (ORRs) and oxygen evolution reactions (OERs) in lithium-oxygen (Li-O2) batteries. In this work, pyridine (Py) functionalized multi-walled carbon nanotubes (MWCNTs) were prepared to immobilize various solid MN4 macrocyclic metal complexes (MN4-MC) as cathode electrocatalysts for Li-O2 batteries. Three types of MN4-MC molecules, including iron phthalocyanine (FePc), cobalt phthalocyanine (CoPc) and iron protoporphyrin IX (Heme) were examined to evaluate the influence of central metal atoms and ligand substituents found in MN4-MC molecules on the electrocatalytic performance of the study samples. The order of the ORR/OER catalytic activity of the bifunctional catalysts is FePc > Heme > CoPc. The central metal atom in FePc molecule has the highest occupied molecular orbital (HOMO) energy than the corresponding metal atoms in CoPc and Heme molecules. This made the molecule to have better dioxygen-binding ability and higher catalytic activity in the ORR process; it also made it to easily lose electrons that were oxidized in the OER process. This study proposed a simplified scheme of the electrode surface route to assist in understanding the diverse ORR/OER performances of MN4-MC. It is discovered that the positive core of the MN5 coordination sphere in MN4-MC/Py/MWCNTs composite is the primary active site that can influence the formation of MN5···O2* and MN5-LOOLi cluster in the ORR process. The interfacial electron could be easily delivered between MWCNTs and MN5 active site through the Py bridge. This facilitated the formation and decomposition of MN5-LOOLi species during the ORRs/OERs, leading to the enhancement of its catalytic performance. This work provides a new insight into the effects of the molecular structure and organization of MN4-MC on the catalytic activity of O2 electrodes in Li-O2 batteries.

Enzyme-responsive macrocyclic metal complexes for biomedical imaging.

Metal chelator-based contrast agents are used as tumor navigators for cancer diagnosis. Although approved metal chelators show excellent contrast performance in magnetic resonance imaging (MRI), large doses are required for cancer diagnoses due to rapid clearance and nonspecific accumulation throughout the body, which can compromise safety. The present study describes an enzyme-responsive metal delivery system, in which enzyme overexpressed in the tumor microenvironment selectively activates the tumor uptake of gadolinium (Gd). Gd was loaded into enzyme-responsive macrocyclam (ErMC) modified with a PEGylated enzyme-cleavable peptide resulting in Gd@ErMC. The PEGylated shell layer protected Gd@ErMC from nonspecific binding in the blood, increasing the half-life of the contrast agent. Specific cleavage of the PEGylated shell layer by the enzyme selectively liberated Gd from Gd@ErMC at the tumor site. Evaluation of the in vivo distribution of Gd@ErMC in tumor-bearing mice by MRI and positron emission tomography (PET) showed that Gd@ErMC had an extended half-life and was highly specific. Histological and serological analysis of Gd@ErMC-treated mice showed that this agent was safe. This novel enzyme-responsive contrast agent delivery system shows promise as specific theranostic agent for MR-guided radiotherapy.

Macrocyclic complexes as potent biomaterial: an experimental study on synthesis, spectroscopic analysis, antioxidant and antimicrobial activity

Macrocyclic complexes as potent biomaterial: an experimental study on synthesis, spectroscopic analysis, antioxidant and antimicrobial activity

Tunable Construction of Sandwich-Type Double-[1 + 1] and Half-Folded [2 + 2] Schiff-Base Complexes Controlled by the Combination of Primary and Secondary Template Effects.

The first-row transition-metal ions Mn2+-Cu2+ could serve as effective templates to construct three types of double-[1 + 1], [2 + 2], and [1 + 1] Schiff-base dinuclear macrocyclic complexes in the presence of dialdehydes with different pendant arms and a common 1,8-diamine. The extremely flexible nature of macrocyclic ligands allows for the multiple template-directed syntheses, but the final products could be finely tuned by the subtle variations of Mn2+-Cu2+ ions in a 3d-electronic configuration, radius, and coordination number/geometry as well as the auxiliary (pendant-armed and anionic) template effect at the same time. Two borderlines are observed at the Co2+ ion for forming double-[1 + 1] and [2 + 2] metallacycles involving the H2pdd precursor and the [1 + 1] Cu2+ complex for double-[1 + 1] and [2 + 2] macrocycles containing the H2hpdd unit, respectively. The structural diversity is originated from the non-perfect match between [1 + 1]/[2 + 2] Schiff-base macrocycles and dinuclear metal centers; hence, a compromise between the metal coordination modes and alterations of the ligand conformation takes place.

Protocols for Understanding the Redox Behavior of Copper-Containing Systems.

Suitability of single-reference density functional theory (DFT) methods for the calculation of redox potentials of copper-containing macrocycle complexes was confirmed by the use of T 1 diagnostics along with a verification of negligible spin contamination or wave function instability. When examining the effect of improvement in the cc-pVnZ basis set series on calculated redox potentials, the results readily converged at the cc-pVTZ level. The all-electron Def2-TZVPP basis set is shown to be a suitable choice of a basis set for the calculation of redox potentials when utilizing a cc-pVTZ geometry. The best-performing model chemistries are determined to be the M06/polarizable continuum model (PCM); therefore, a scheme for redox potential calculations of copper macrocycles using either M06/cc-pVTZ with PCM solvation is proposed to reliably reproduce experimental trends.

In vitro cytotoxicity and antimicrobial evaluation of novel 24–28 membered Schiff base octaazamacrocyclic complexes of manganese(II): Synthesis, characterization, DFT and molecular docking studies

The development of novel metal-based molecular antibiotics is an effective strategy to combat the rising threat of cancer and microbial diseases. In this view, novel Schiff base octaazamacrocyclic complexes of Mn(II) were synthesized using 2:2 molar ratio of macrocyclic ligands derived from Schiff base ligand [L] and dicarboxylic acids. The synthesized compounds were characterized by infra-red, 1H NMR, 13C NMR, ESI-mass, UV–visible, EPR, and powder X-ray diffraction spectral studies, together with elemental (CHN) analysis, molar conductance, and magnetic susceptibility measurements. Calculations based on density functional theory (DFT) help in determining the stability of synthesized macrocylic ligands. Electronic spectra led to the assignment of an octahedral geometry to the synthesized macrocyclic complexes. In vitro cytotoxicity of macrocyclic ligands and their Mn(II) complexes was examined against three distinct cancerous cell lines, including HeLa, A549, and MCF7 cells. The observed IC50 values for the tested compounds against cancerous cell lines demonstrate a relatively good level of cytotoxicity. Molecular docking of Schiff base macrocyclic ligands supported their cytotoxic potential against the tested cell lines. Moreover, the antimicrobial activity of the synthesized compounds was also evaluated against bacterial (E. coli, B. subtilis) and fungal strains (C. albicans, F. oxysporum). The results indicate that the macrocyclic Mn(II) complexes have more antimicrobial potential than macrocyclic ligands against tested pathogens.

Nanoscale synthesis, structural elucidation, DFT, and biological activity of amide appended transition metal(II) macrocyclic complexes in drug delivery system

Nanoscale complexes of Mn(II), Ni(II), and Cu(II) with 6,15-diamino-1,4,9,12-tetraazacyclohexadecane-5,8,13,16-tetraone were synthesized by ultrasonic sonication method. The Fourier-transform infrared (FTIR) spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, carbon, hydrogen, and nitrogen elemental (CHN) analysis, mass spectrometry (MS), and electron spin resonance (ESR) spectroscopy were used to identify and suggest the structure of the synthesized nanocomplexes. The field emission scanning electron microscopy (FE-SEM) and powder X-ray diffraction (PXRD) revealed that the size of the synthesized nanocomplexes was 44–58 nm. Based on these studies, hexagonal, monoclinic, and cubic unit cell structure has been proposed for the synthesized Mn(II), Ni(II), and Cu(II), respectively. The theoretical calculations of the synthesized nanocomplexes were carried out by a GAUSSIAN 09 program involving geometry optimization and bond parameters using the B3LYP method. Moreover, binding energy, HOMO, and LUMO have been calculated. In addition, hardness, softness, chemical potential, and dipole moment were calculated for ligand and its metal nanocomplexes. The biological efficacy of the synthesized nanocomplexes was examined and found to be better and highly effective drug delivery system (DDS) for the antimicrobial and antioxidative agent.

Encapsulation of (E)-N’-(1-(7-(diethylamino)-2-oxo-2H-chromen-3 yl)ethylidene)benzohydrazide (7-diEAHC) in β-cyclodextrins: Optimized synthesis of 7-diEACH and in silico ADME profiling, physical stability, antioxidant properties of encapsulated 7-diEAHC and bioavailability in rats

The β-cyclodextrins (β-CD) as supramolecular have extremely attractive pharmaceutical applications. This study focused on the effects of macrocyclic systems complexation on stability, antioxidant activities, and bioavailability of the optimized synthesis coumarin incorporating hydrazone moiety. Optimal synthesis of (E)-N’-(1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (7-diEAHC) was performed by using response surface methodology (RSM) with a temperature of 100 °C, a reaction time of 10 min in the presence of acetic acid (0.85 M). Physicochemical properties and in silico ADME profiling of 7-diEAHC were also determined. The encapsulation efficiencies of the 7-diEAHC were above 81 % for the micro-encapsulates. After sunlight exposure, the 7-diEAHC-β-CD inclusion complex showed a photostability 19.4 % higher than free 7-diEAHC. Additionally, the encapsulated 7-diEAHC exhibited better stability than free 7-diEAHC for the pH varied between 1 and 9. From the results, storage stability showed that the encapsulation method using β-CD conferred a greater ability of 7-diEAHC against temperature. The NMR and FT-IR techniques were employed to evaluate the chemical stability of 7-diEAHC after encapsulation. In addition, in vivo study showed that the micro-encapsulation approach increased the oral bioavailability of 7-diEAHC in treated rats.

Synthetic approaches to metal-coordination-directed macrocyclic complexes.

Metal-coordination-directed macrocyclic complexes, in which macrocyclic architectures are formed by metal-ligand coordination interactions, have emerged as attractive supramolecular scaffolds for the creation of materials for applications in biosensing and therapeutics. Despite recent progress, uncontrolled multicyclic cages and linear oligomers/polymers is the most likely outcome from metal-ligands assembly, representing a challenge to current synthetic methods. Herein we outlined the state-of-art synthetic approaches to the metal-coordination-directed macrocyclic complexes by using foldable ligands or through assembly of amphiphilic ligands. This mini-review offers a guideline for the efficient preparation of metal-coordination-directed macrocyclic complexes with predictable and controllable structures, which may find applications in many biology-related areas.

Structure of a dinickel(II)-dithiolate bridged macrocyclic complex synthesised via a novel solvent-assisted disulfide cleavage reaction

The reaction of 2,6-diformyl-4-methylphenyl disulfide with [Ni(tn)3]Cl2 (tn = 1,3-diaminopropane), in methanol and in the presence of NaBPh4 resulted in the isolation of [Ni2(L1)](DMF)2(BPh4)2 (I), (L1 = 15,95-dimethyl-3,7,11,15-tetraaza-1,9(1,3)-dibenzenacyclohexadecaphane-2,7,10,15-tetraene-12,92-bis(thiolate). This reaction represents a 2-electron solvent assisted reduction of the disulfide bond to form two thiolate ligands where methanol is converted to formaldehyde and the two nickel centres remained in the + 2 oxidation state. The crystal structure of I showed the two nickel(II) atoms are bridged by two thiolates in a binuclear Ni2S2 core inside of a macrocyclic framework. The IR spectrum showed a band at 1625 cm−1, assigned to the imine ν(C N) stretch of the macrocyclic ligand, and bands at 734, 706 cm−1, are assigned to the tetraphenylborate counter ions. This is the first example of solvent assisted SS bond cleavage being used to prepare a dicompartmental macrocyclic complex.

Synthesis, Spectroscopic Characterization, Biocidal evaluation Molecular Docking & DFT Investigation of 16-18 membered Macrocyclic Complexes of Cobalt (II).

Antimicrobial, DFT, and Docking representation of Cobalt (II) macrocyclic complexes. The online version contains supplementary material available at 10.1007/s12039-022-02109-2.

Macrocyclic Supramolecular Assemblies Based on Hyaluronic Acid and Their Biological Applications.

Hyaluronic acid (HA), which contains multiple carboxyl, hydroxyl, and acetylamino groups and is an agent that targets tumors, has drawn great attention in supramolecular diagnosis and treatment research. It can not only assemble directly with macrocyclic host-guest complexes through hydrogen bonding and electrostatic interactions but also can be modified with macrocyclic compounds or functional guest molecules by an amidation reaction and used for further assembly. Macrocycles play a main role in the construction of supramolecular drug carriers, targeted imaging agents, and hydrogels, such as cyclodextrins and cucurbit[n]urils, which can encapsulate photosensitizers, drugs, or other functional guest molecules via host-guest interactions. Therefore, the formed supramolecular assemblies can respond to various stimuli, such as enzymes, light, electricity, and magnetism for controlled drug delivery, enhance the luminescence intensity of the assembly, and improve drug loading capacity. In addition, the nanosupramolecular assembly formed with HA can also improve the biocompatibility of drugs, reduce drug toxicity and side effects, and enhance cell permeability; thus, the assembly has extensive application value in biomedical research. This Account mainly focuses on macrocyclic supramolecular assemblies based on HA, especially their biological applications and progress in the field, and these assemblies include (i) guest-modified HA, such as pyridinium-, adamantane-, peptide-, and other functional-group-modified HA, along with their cyclodextrin and cucurbit[n]uril assemblies; (ii) macrocycle-modified HA, such as HA modified with cyclodextrins and cucurbit[n]uril derivatives and their assembly with various guests; (iii) direct assembly between unmodified HA and cyclodextrin- or cucurbit[n]uril-based host-guest complexes. Particularly, we discussed the important role of macrocyclic host-guest complexes in HA-based supramolecular assembly, and the roles included improving the water solubility and efficacy of hydrophobic drugs, enhancing the luminescent intensity of assemblies, inducing room temperature phosphorescence and providing energy transfer systems, constructing multi-stimulus-responsive supramolecular assemblies, and in situ formation of hydrogels. Additionally, we believe that obtaining in-depth knowledge of these HA-based macrocyclic supramolecular assemblies and their biological applications encompasses many challenges regarding drug carriers, targeted imaging agents, wound healing, and biomedical soft materials and would certainly contribute to the rapid development of supramolecular diagnosis and treatment.

Electrocatalytic hydrogen evolution from water at low overpotentials with cobalt complexes supported by redox-active bipyridyl-NHC donors

AbstractThree cobalt complexes bearing tunable, redox-active bipyridyl N-heterocyclic carbene (NHC)-based ligands have been studied for electrocatalytic hydrogen evolution from aqueous solutions. The effect of structural modifications to the ligand framework is investigated across the catalyst series, which includes a non-macrocyclic derivative (1-Co) and 16-(2-Co) and 15-(3-Co) membered macrocycles. A structure-activity relationship is demonstrated, in which the macrocyclic complexes have greater activity compared to their non-macrocyclic counterpart with the most rigid catalyst, supported by the 15-membered macrocycle, performing best overall. Indeed, 3-Co catalyzes H2 evolution from aqueous pH 4 acetate buffer with a Faradaic efficiency of 97% at a low overpotential of 330 mV. Mechanistic studies are consistent with formation of a cobalt-hydride species that is subsequently protonated to evolve H2 via a heterolytic pathway.

Crownphyrins: Metal‐Mediated Transformations of the Porphyrin‐Crown Ether Hybrids

AbstractCrownphyrins are hybrid macrocycles combining structural features of porphyrin and crown ethers. The molecular architecture renders them an intriguing class of hosts capable of binding neutral, and ionic guests. The presence of dynamic covalent imine linkages connecting the dipyrrin segment with the ether chain enables unusual coordination behavior of crownphyrins, as demonstrated by the formation of two classes of strikingly different complexes. The remarkable metal‐mediated expansion to the helical [2+2] macrocyclic complex is reversible. The reaction of the figure‐eight mercury(II) assembly with [2.2.2]cryptand results in ring contraction providing the metal‐free crownphyrin macrocycle.

Crownphyrins: Metal-Mediated Transformations of the Porphyrin-Crown Ether Hybrids.

Crownphyrins are hybrid macrocycles combining structural features of porphyrin and crown ethers. The molecular architecture renders them an intriguing class of hosts capable of binding neutral, and ionic guests. The presence of dynamic covalent imine linkages connecting the dipyrrin segment with the ether chain enables unusual coordination behavior of crownphyrins, as demonstrated by the formation of two classes of strikingly different complexes. The remarkable metal-mediated expansion to the helical [2+2] macrocyclic complex is reversible. The reaction of the figure-eight mercury(II) assembly with [2.2.2]cryptand results in ring contraction providing the metal-free crownphyrin macrocycle.

Synthesis, spectral, biological, and computational studies of template engineered macrocyclic metal complexes

A series of macrocyclic Cu2+, Ni2+, and Co2+ complexes was synthesized using a template reaction between triethylenetetramine and dibenzoylmethane. These complexes may be represented by the general formula [M(C21H26N4)X2], where M = Cu2+, Ni2+, and Co2+ and X = NO3ˉ, Clˉ, and CH3COOˉ. Various techniques, including elemental analysis, molar conductance, magnetic moment, PXRD, thermal investigations, EPR, IR, UV-visible, and mass spectral studies, were used to characterize the synthesized complexes. Their results suggested the distorted octahedral geometry for copper complexes and octahedral geometry for nickel and cobalt complexes. All complexes showed molar conductance in the range of 8–20 ohm−1 cm2 mol−1 that indicated the non-electrolytic nature. The DFT studies of all complexes were also performed to analyze the stability of complexes. Antibacterial activities of all complexes were also examined, and it was observed that complexes [Ni(C21H26N4)(Cl)2] and [Co(C21H26N4)(Cl)2] exhibited remarkable antibacterial activity. Moreover, complex [Co(C21H26N4)(NO3)2] showed miraculous antioxidant activity, even better than that of ascorbic acid and other complexes. The docking studies of [Ni(C21H26N4)(Cl)2] and [Co(C21H26N4)(Cl)2] were also performed to enforce the results obtained from the antibacterial study of these complexes. Furthermore, the drug-likeness property of all complexes was also evaluated with the help of ADMET studies.

Schiff Base Complexes with Covalently Anchored Luminophores: Self-Enhanced Electrochemiluminescence Detection of Neomycin.

A novel electrochemiluminescence (ECL) amplification strategy was established aiming to overcome the inherent shortcomings of the current oxygen (O2) coreactant ECL systems. Macrocyclic Schiff base Fe complexes were rationally designed as a novel integrated ECL emitter by iminium linkage between N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and 1,10-phenanthroline-2,9-dicarbaldehyde (PDL) and postmetalation of the macrocyclic Schiff base. Covalently combining luminophore ABEI with a catalytic center endowed the novel ECL emitter with both remarkable redox electrocatalytic properties and significantly enhanced ECL efficiency. The high content of ferrous iron and the dominantly active low-spin Fe state greatly contributed to the inherent catalytic activity for O2 activation. The rational modification of luminophore optimized the spatial distribution and simultaneously shortened the species transport distance of coreactant radicals generated in situ from dissolved O2, resulting in significantly self-enhanced ECL efficiency. Neomycin, which posed a growing threat to aquatic biodiversity and environmental safety, as the model antibiotic was successfully detected with a detection limit of 0.21 pM (S/N = 3), clarifying a promising application prospect of this new luminophore-embedded ECL amplification strategy in biological analysis and environmental monitoring.

Molecular Catalyst Synthesis Strategies to Prepare Atomically Dispersed Fe-N-C Heterogeneous Catalysts.

We report a strategy to integrate atomically dispersed iron within a heterogeneous nitrogen-doped carbon (N-C) support, inspired by routes for metalation of molecular macrocyclic iron complexes. The N-C support, derived from pyrolysis of a ZIF-8 metal-organic framework, is metalated via solution-phase reaction with FeCl2 and tributyl amine, as a Brønsted base, at 150 °C. Fe active sites are characterized by 57Fe Mössbauer spectroscopy and aberration-corrected scanning transmission electron microscopy. The site density can be increased by selective removal of Zn2+ ions from the N-C support prior to metalation, resembling the transmetalation strategy commonly employed for the preparation of molecular Fe-macrocycles. The utility of this approach is validated by the higher catalytic rates (per total Fe) of these materials relative to established Fe-N-C catalysts, benchmarked using an aerobic oxidation reaction.

Luminescence of Macrocyclic Mononuclear DyIII Complexes and Their Immobilization on Functionalized Silicon-Based Surfaces.

Two mononuclear DyIII complexes, [Dy(L1)(NCS)3] (Dy-EDA) and [Dy(L2)(NCS)3] (Dy-DAP), where Ln (n = 1-2) corresponds to a macrocyclic ligand derived from 2,6-pyridinedicarboxaldehyde and ethylenediamine (L1) and 1,3-diaminepropane (L2) were immobilized on functionalized silicon-based surfaces. This was achieved by the microcontact printing (μCP) technique, generating patterns on a functionalized surface via covalent bond formation through the auxiliary -NCS ligands present in the macrocyclic complex species. With this strategy, it was possible to control the position of the immobilized molecules on the surface. Water contact angle measurements, X-ray photoelectron spectroscopy (XPS), infrared reflection absorption spectra (IRRAS), and atomic force microscopy (AFM) confirmed that the surfaces were successfully functionalized. Furthermore, the optical properties in a broad temperature range were investigated for the as-prepared compounds. At room temperature, Dy-EDA was shown to emit in the deep blue region (Commission Internationald'Eclairage (CIE): (0.175, 0.128)), while Dy-DAP in the white region (CIE: (0.252, 0.312)). The different CIE values were due to the contribution of the strong emission of the ligand in the case of Dy-EDA. Besides, surface photoluminescence measurements showed that the immobilized complexes retained their bulk emissive properties.