Macrocyclic Ligand Research Articles

Maximizing the Potential of Electrically Conductive MOFs.

ConspectusElectrically conductive metal-organic frameworks (EC-MOFs) have emerged as a compelling class of materials, drawing increasing attention due to their unique properties facilitating charge transport within porous structures. The synergy between electrical conductivity and porosity has opened a wide range of applications, including electrocatalysis, energy storage, chemiresistive sensing, and electronic devices that have been underexplored for their insulating counterparts. Despite these promising prospects, a prevalent challenge arises from the predominant adoption of two-dimensional (2D) structures by most EC-MOFs. These 2D frameworks often show modest surface areas and short interlayer distances, hindering molecular accessibility, which deviates from the inherent characteristics of conventional MOFs. Furthermore, the quest for efficient charge transport imposes design constraints, leading to a restricted selection of functional building blocks. Additionally, there is a lack of established functionalization methods within EC-MOFs, limiting their functional diversity. Thus, these challenges have impeded EC-MOFs from reaching their full potential.In this Account, we summarize and discuss our group's efforts aimed at enhancing molecular accessibility and deploying the functional diversity of EC-MOFs. Our focus on enhancing molecular accessibility involves several strategies. First, we employed macrocyclic ligands with intrinsic pockets as the building blocks for EC-MOFs. The integrated intrinsic pockets in the frameworks supplement surface areas and additional pores to enhance molecular accessibility. The resulting macrocyclic ligand-based EC-MOFs exhibit exceptionally high surface areas and confer advantages in electrochemical performances. Second, our efforts extend to addressing the structural limitations, frequently associated with EC-MOFs' 2D structures. Through the pillar insertion strategy, we transformed a 2D EC-MOF platform into a three-dimensional (3D) structure, thereby achieving higher porosity and enhanced molecular accessibility. In pursuing functional diversity, we have delved into molecular-level tuning of EC-MOF building blocks. We demonstrated that electron-rich alkyne-based pockets in the macrocyclic ligands can host transition metals and alkali ions, enabling ion selectivity and showcasing diverse use of EC-MOFs. We utilized a postsynthetic approach to further functionalize metal nodes on the molecular level within an EC-MOF framework, introducing a proton-conducting pathway while preserving its electrical conductivity.We aspire for this Account to provide practical insights and strategies to surmount structural and functional diversity limitations in the realm of EC-MOFs. By integrating enhanced molecular accessibility and diverse functionality, our endeavor to propel the utility of these materials will inspire further rational development for future EC-MOFs and unlock their full potential.

Perspectives on Nuclear Magnetic Resonance Spectroscopy in Drug Discovery Research.

The drug discovery landscape has undergone a significant transformation over the past decade, owing to research endeavors in a wide range of areas leading to strategies for pursuing new drug targets and the emergence of novel drug modalities. NMR spectroscopy has been a technology of fundamental importance to these research pursuits and has seen its use expanded both within and outside of traditional medicinal chemistry applications. In this perspective, we will present advancement of NMR-derived methods that have facilitated the characterization of small molecules and novel drug modalities including macrocyclic peptides, cyclic dinucleotides, and ligands for protein degradation. We will discuss innovations in NMR spectroscopy at the chemistry and biology interface that have broadened NMR's utility from hit identification through lead optimization activities. We will also discuss the promise of emerging NMR approaches in bridging our understanding and addressing challenges in the pursuit of the therapeutic agents of the future.

First‐Row Transition‐Metal Complexes with Tetra‐Amido Macrocyclic Ligands for Water and C(sp3)−H Bond Oxidation: Performance Benchmarking Using Free Energy Relationships

AbstractThe catalytic oxidation of water and C(sp3)−H bonds enables the conversion of solar/electrochemical energy into chemical energy and alcohol fuel production, respectively, and therefore plays important roles in energy conversion/storage. These transformations are typically catalyzed by the highly active complexes of the earth‐abundant first‐row transition metals (Mn, Fe, Co, Ni, and Cu) with tetra‐amido macrocyclic ligands (TAMLs), although the related kinetics and thermodynamics remain underexplored. This review uses free energy relationships between kinetic and thermodynamic descriptors as normalized metrics to benchmark/compare these TAML‐based catalysts and assess the advances in their development.

Tuning the Softness of the Pendant Arms and the Polyazamacrocyclic Backbone to Chelate the 203Pb/212Pb Theranostic Pair.

A series of macrocyclic ligands were considered for the chelation of Pb2+: 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetrazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetrazacyclotetradecane (TE4S). The equilibrium, the acid-mediated dissociation kinetics, and the structural properties of the Pb2+ complexes formed by these chelators were examined by UV-Visible and nuclear magnetic resonance (NMR) spectroscopies, combined with potentiometry and density functional theory (DFT) calculations. The obtained results indicated that DO4S, DO3S, DO3SAm, and DO2A2S were able to efficiently chelate Pb2+ and that the most suitable macrocyclic scaffold for Pb2+ is 1,4,7,10-tetrazacyclododecane. NMR spectroscopy gave insights into the solution structures of the Pb2+ complexes, and 1H-207Pb interactions confirmed the involvement of S and/or O donors in the metal coordination sphere. Highly fluxional solution behavior was discovered when Pb2+ was coordinated to symmetric ligands (i.e., DO4S and DO2A2S) while the introduction of structural asymmetry in DO3S and DO3SAm slowed down the intramolecular dynamics. The ligand ability to chelate [203Pb]Pb2+ under highly dilute reaction conditions was explored through radiolabeling experiments. While DO4S and DO3S possessed modest performance, DO3SAm and DO2A2S demonstrated high complexation efficiency under mild reaction conditions (pH = 7, 5 min reaction time). The [203Pb]Pb2+ complexes' integrity in human serum over 24 h was appreciably good for [203Pb][Pb(DO4S)]2+ (80 ± 5%) and excellent for [203Pb][Pb(DO3SAm)]2+ (93 ± 1%) and [203Pb][Pb(DO2A2S)] (94 ± 1%). These results reveal the promise of DO2A2S and DO3SAm as chelators in cutting-edge theranostic [203/212Pb]Pb2+ radiopharmaceuticals.

A bifunctional fluorescent sensor based-on Pillar[5]arene for efficient detection of MnO4− as an oxidant and Hg2+ ion in aqueous media: Bio-imaging in living cells

The high amounts of oxidants and heavy metal ions caused undesirable health results and the detection of these ions gained increasing importance with new techniques. This paper focuses on a fluorescent macrocyclic sensor based on Pillar[5]arene and Bodipy (Bodipy-P[5]arene) for the recognition of oxidants and heavy metal ions in aqueous solution. After the characterization of the macrocyclic ligand, the spectroscopic measurements were carried out by Uv–vis and fluorescence spectroscopies. The bifunctional fluorescent macrocycle, Bodipy-P[5]arene, presents to a dual effect with fluorescence quenching response for fluorometrically recognizing MnO4- and Hg2+ ions. Bodipy-P[5]arene has low detection limits of MnO4- and Hg2+ such as 1.15 × 10-7 M and 8.12 × 10-7 M, respectively. Moreover, both Bodipy-P[5]arene can respectively detect the target ions in acidic and basic mediums and the macrocyclic ligand has short response times. In addition, the Bodipy-P[5]arene probe demonstrates low cellular toxicity and exceptional membrane permeability, making it a successful tool for fluorescently imaging Hg2+ and MnO4- ions within living HeLa cells.

Novel amide based macrocyclic complexes of Co(II): Synthesis, structural characterization, thermal, DFT, molecular docking studies, in vitro cytotoxic, antimicrobial and antioxidant evaluation

The novel cobalt (II) macrocyclic complexes [Co(N4O4MacL1)Cl2]-[Co(N4O4MacL3)Cl2] have been synthesized by using the macrocyclic ligands [N4O4MacL1], [N4O4MacL2] and [N4O4MacL3] that have an N4O4 core. To investigate Co(II), metal complexes [Co(N4O4MacL1)Cl2]-[Co(N4O4MacL3)Cl2] with new ligands, elemental analyses, infrared, magnetic measurements, UV–visible, 1H NMR, 13C NMR, and XRD studies were utilised. According to the spectrum data, the ligands perform as a mononegative tetradentate. Based on magnetic and electronic spectrum data, an octahedral structure for Co(II) metal complexes has been postulated. The Coats-Redfern and FWO techniques are used to determine the thermodynamic characteristics of ligands and their complexes. The molecular modelling using the DFT technique displays bond angles, bond lengths, and quantum chemical factors. To determine their ability to prevent the growth of harmful fungus and bacteria, the ligands [N4O4MacL1]- [N4O4MacL3] and their complexes were tested in vitro against A. Niger, C. albicans and B. subtilis, S. aureus, E. coli and S. typhi fungal and bacterial organisms, respectively. By using DPPH free radical scavenger assays, the in vitro antioxidant capabilities of each compound were evaluated. The [Co(N4O4MacL3)Cl2] antioxidative capabilities revealed significant radical scavenging power. All of the compounds under research were examined for cytotoxicity using the MTT assay on MCF-7 and HepG-2 cells, and the findings revealed that [Co(N4O4MacL2)Cl2] show outstanding cytotoxic activity against HepG-2 with IC50 17.94 ± 045 at a concentration of 25 ppm. Additionally, docking investigations of the produced compounds were carried out in order to validate the biological outcomes. Considerably, the current Co (II) complexes with their effective antimicrobial, antioxidant, and cytotoxicity activity would be probably appraised for further medicinal and pharmaceutical applications.

A novel µ-carbido hetero-binuclear iron-ruthenium heteroleptic complex on macrocyclic platforms with efficient oxidative activity

Bimetallic µ-bridged complexes supported by macrocycles are worth addressing due to their excellent stability, rich redox chemistry and suitability in catalysis. This paper for the first-time reports on the synthesis and redox properties of an unexplored heterometallic μ-carbido-dimer derivative bearing iron-porphyrin and ruthenium-phthalocyanine parts and a FeIV = C = RuIV unit. The compound is identified by UV–visible, IR, EPR, MALDI TOF, electrochemistry techniques and DFT calculations. The redox activity of the compound toward H2O2, tBuOOH is examined. The results indicate that under oxidation conditions in dichloromethane, benzene and acetonitrile, the initial complex evolves rapidly via oxidation steps forming intermediates which are competent in β-carotene and methylene blue oxidation at room temperature. The site oxidation accessibility of the initial compound and the nature of high-charged intermediate species are established to depend on the solvent polarity and axial ligands. The findings contribute to a deeper understanding of the significant role of reaction conditions as well as the mixed macrocyclic ligand environment and metal nature in controlling the oxidizing capability and thus can aid the development of new more active and durable catalysts.

DESIGN, SYNTHESIS, SPECTRAL ANALYSIS, ANTIMICROBIAL EVALUATION AND TOXICOLOGICAL ASPECTS OF BIVALENT TIN COMPLEXES WITH MACROCYCLIC MOIETY

The novel complexes Sn(II), were synthesized of macrocyclic ligands derived from various diamine and dicarboxylic acids in the ratio of 2:2 and characterized by elemental analysis, molar conductance measurements, mass, NMR, FT-IR, and electronic spectra. The interactions of macrocyclic ligands (MLn) with SnCl2 in a 1:1 molar ratio in methanol produced the ensuing physiologically active [Sn(MLn)Cl2] type complexes, where n = 1 or 2. The complexes were initially identified using conductivity tests, molecular weight calculations, and elemental investigations. The bonding mode was determined using spectral data from the IR, 1H NMR, and 119Sn NMR. The complexes exhibit hexacoordinated octahedral geometry. The positive findings of Brine shrimp lethality of the ligands and their complexes have been discussed. The antimicrobial effects of each complex on several types of harmful fungus and bacteria have been assessed. The research focused on investigating and analyzing various aspects related to male fertility. It specifically investigated cauda epididymal spermatozoa density, sperm motility, testicular sperm density, fertility, and biological constraints of propagative tissues. The findings and discussions about these factors were presented in the study.

A rhodium(II)/rhodium(III) redox couple for C-H bond amination with alkylazides: a rhodium(III)-nitrenoid intermediate with a tetradentate [14]-macrocyclic ligand.

The catalytic activity of a rhodium(II) dimer complex, [RhII(TMAA)]2 (TMAA = tetramethyltetraaza[14]annulene), in C-H amination reactions with organic azides is explored. Organic azides (N3-R) with an electron-withdrawing group such as a sulfonyl group (trisylazide; R = S(O)2iPr3C6H2 (Trs)) and a simple alkyl group (R = (CH2)4Ph, (CH2)2OCH2Ph, CH2Ph, or C6H4NO2) are employed in intra- and intermolecular C-H bond amination reactions. The spectroscopic analysis using ESI-mass and EPR spectroscopy techniques on the reaction intermediate generated from [RhII(TMAA)]2 and N3-R reveals that a rhodium(III)-nitrenoid species is an active oxidant in the C-H bond amination reaction. DFT calculations suggest that the species can feature a radical localised nitrogen atom. The DFT calculation studies also indicate that the amination reaction involves hydrogen atom abstraction from the organic substrate R'-H by the NR moiety of 2N˙R and successive rebound of the generated organic radical intermediate R'˙ to [RhIII(NH-R)(TMAA)], giving [RhII(TMAA)] and R'-NH-R (amination product).

Construction of zirconium/hafnium-oxo clusters based on a new protection-calix[8]arene.

Calix[8]arene has been used as a promising type of macrocyclic ligand for the construction of multinuclear metal-oxo clusters (MOCs), but not for zirconium/hafnium-oxo clusters (Zr/HfOCs). In this paper, we report the first series of ZrOCs (HfOCs) based on calix[8]arene: Zr4, Zr8, Hf4, and Hf8. Zr8/Hf8 has a rhombohedral conformation and can be regarded as a derivative of the octahedral Zr6 cluster. Remarkably, I2 adsorption experiments indicate that Zr4 (Zr8) adsorbs much faster than Hf4 (Hf8). Density functional theory (DFT) calculations show that metallic Zr atoms interact more strongly with I2 than metallic Hf atoms. The successful application of calix[8]arene for the synthesis of well-defined ZrOCs (HfOCs) shows a bright future for MOCs protected by macrocyclic ligands.

Coordination compounds with subporphyrazine may exist: DFT quantum chemical prediction for M(ii) complexes with a given macrocyclic ligand (M = Ti–Zn)

The existence of macrotricyclic complexes containing M(ii) ion (M = Ti–Zn) and double deprotonated form of subporphyrazine that is unknown for these 3d-elements, was shown by quantum-chemical calculation using three various DFT methods.

Capture of mechanically interlocked molecules by rhodium-mediated terminal alkyne dimerisation.

The transition metal-mediated dimerisation of terminal alkynes is an attractive and atom-economic method for preparing conjugated 1,3-enynes. Using a phosphine-based macrocyclic pincer ligand, we demonstrate how this transformation can be extended to the synthesis of novel, hydrocarbon-based interlocked molecules: a rotaxane by 'active' metal template synthesis and a catenane by sequential 'active' and 'passive' metal template procedures.

Sulfonylcalix[4]arene-based Al4 clusters: three aluminum oxo clusters with different coordinated solvents for the CO2 cycloaddition reaction

By using a macrocyclic H4BTC4A-SO2 ligand, we successfully synthesized three Al4 clusters with different solvents, which exhibit different potentials to expose metal active sites for the catalytic reaction. of cycloaddition of carbon dioxide.

Understanding solvent polarity effects on the separation of uranyl porphyrin-derivative complexes.

Solvation is a crucial task in developing efficient and selective extractants for actinide elements, but an understanding and perspective of solvent effects on the extraction of uranyl are still lacking. Herein, we present investigations into solvent effects on the geometry, stability and bonding properties of five uranyl porphyrin derivative complexes (UO2(L)) in four solvents via relativistic quantum chemical calculations, and reveal some trends in the influence of solvent polarity on uranyl compounds. All five [L]2- ligands equatorially coordinate [UO2]2+ in a hexa-dentate (κ6) fashion. Thus, the uranium center is bound to six N atoms by U-N bonds, and the properties of the U-N bond are affected by the ligands rather than by the solvent. The relative stability of these UO2(L) complexes is obviously affected by the solvent polarity; lower polar solvents stabilize more UO2(L) complexes from higher polar solvents, resulting in more extensive interaction of U-N. By computing the reaction energy, we track the conversion of pure [UO2]2+ to UO2(L) complexes in different solvents; the uranyl dipentafluorobenziamethyrin species exhibit the greatest selectivity to higher polarity solvents, with significant orbital interactions of U-N accounting for this stability and selectivity. This study provides a general procedure for theoretical screening of the binding ability and solvent selectivity of macrocyclic ligands towards uranyl, and searching for suitable ligands and solvents that will later be applied in nuclear science disciplines.

High-valent nonheme Fe(IV)O/Ru(IV)O complexes catalyze C-H activation reactivity and hydrogen tunneling: a comparative DFT investigation.

A comprehensive density functional theory investigation has been presented towards the comparison of the C-H activation reactivity between high-valent iron-oxo and ruthenium-oxo complexes. A total of four compounds, e.g., [Ru(IV)O(tpy-dcbpy)] (1), [Fe(IV)O(tpy-dcbpy)] (1'), [Ru(IV)O(TMCS)] (2), and [Fe(IV)O(TMCS)] (2'), have been considered for this investigation. The macrocyclic ligand framework tpy(dcbpy) implies tpy = 2,2':6',2''-terpyridine, dcbpy = 5,5'-dicarboxy-2,2'-bipyridine, and TMCS is TMC with an axially tethered -SCH2CH2 group. Compounds 1 and 2' are experimentally synthesized standard complexes with Ru and Fe, whereas compounds 1' and 2 were considered to keep the macrocycle intact when switching the central metal atom. Three reactants including benzyl alcohol, ethyl benzene, and dihydroanthracene were selected as substrates for C-H activation. It is noteworthy to mention that Fe(IV)O complexes exhibit higher reactivity than those of their Ru(IV)O counterparts. Furthermore, regardless of the central metal, the complex featuring a tpy-dcbpy macrocycle demonstrates higher reactivity than that of TMCS. Here, a thorough analysis of the reactivity-controlling characteristics-such as spin state, steric factor, distortion energy, energy of the electron acceptor orbital, and quantum mechanical tunneling-was conducted. Fe(IV)O exhibits the exchanged enhanced two-state-reactivity with the quintet reactive state, whereas Ru(IV)O has only a triplet reactive state. Both the distortion energy and acceptor orbital energy are low in the case of Fe(IV)O supporting its higher reactivity. All the investigated C-H activation processes involve a significant contribution from hydrogen tunneling, which is more pronounced in the case of Ru, although it cannot alter the reactivity pattern. Furthermore, it has also been found that, independent of the central metal, aliphatic hydroxylation is always preferable to aromatic hydroxylation. Overall, this work is successful in establishing and investigating the cause of enzymes' natural preference for Fe over Ru as a cofactor for C-H activation enzymes.

Macrocyclic ligands open new channels in electrically conductive metal-organic frameworks

Macrocyclic ligands open new channels in electrically conductive metal-organic frameworks

Synthesis, structural and magnetic properties of cobalt(ii) complexes with pyridine-based macrocyclic ligand containing two pyridine pendant arms.

With the aim of tuning the magnetic anisotropy, a series of Co(ii) complexes with the general formula of complex cations [Co(L)X]+, where X = Br- (1); I- (2); NCO- (3); NCS- (4a); N3 - (5), and [Co(L)(NCS)2] (4b), (L = a 17-membered pyridine-based N3O2-macrocyclic ligand containing two pyridin-2-ylmethyl pendant arms) were prepared and thoroughly characterized. The molecular structures for all complexes showed strongly distorted geometry in between octahedral and trigonal prismatic. The magnetic studies confirmed substantial magnetic anisotropy with positive values of D, the axial zero-field splitting parameter, but E/D ratios close to 1/3. This was supported by theoretical CASSCF calculations showing no significant effect of the co-ligands. Complex 4b was found to behave as a field-induced SMM.

One-pot gram-scale rapid synthesis of MN4 complexes with 14-membered ring macrocyclic ligand as a precursor for carbon-based ORR and CO2RR catalysts.

Herein, CoN4, CuN4, and NiN4 complexes with a 14-membered ring hexaazamacrocycle ligand H2HAM were synthesised as precursors for ORR and CO2RR catalysts via a one-pot, gram-scale synthesis procedure, which involved microwave heating for only 10 min. Detailed structures of the obtained 14MR-MN4 complex were revealed by single-crystal X-ray diffraction measurements.

Investigation of Antiviral Activities of Nickel and Copper Complexes with Macrocyclic Ligands against Crimean-Congo Hemorrhagic Fever by In Silico Calculations

For the first time, electronic characteristics of potential drug candidates and their inhibitory activities have been linked thanks to this work. Synthesized copper and nickel complexes with trans-N1,N8-bis(2-cyanoethyl)-2,4,4,9,11,11-hexamethyl-1,5,8,12-tetraazacyclotetradecane (tet-bx) ligand, as well as the proposed hypothetical complexes, were properly examined by the appropriate calculation method in atomic and molecular dimensions. The appropriate calculation level was achieved by using the IR spectroscopic data of the tet-bx ligand. The experimental and calculated bond stretching frequencies were compared for synthesized complexes [Ni(tet-bx)](ClO4)2 (1), [Cu(tet-bx)](ClO4)2 (2), [Ni(tet-bx)(NCS)2] (3), and [Ni(tet-bx)(ClO4)Cl] (5). Some bond stretching frequencies of hypothetical complexes [Cu(tet-bx)(NCS)2] (4) and [Cu(tet-bx)(ClO4)Cl] (6) have also been proposed and their molecular structure were determined. To analyze the electronic behavior of the examined complexes at the atomic level, Fukui function indices (nucleophilic f+ and electrophilic f- populations) were determined. Furthermore, antibacterial and antiviral inhibition efficiency of the complexes against Crimean-Congo hemorrhagic fever has been investigated by docking studies

A new family of macrocyclic antibiotics based-on Pillar[5]arene concluding multi quinoline moieties

Due to the many negative effects of increasing resistance to traditional antibiotics on living organisms, the development of new antibiotic classes has become imperative and macrocyclic compounds come to the fore for the solution of this problem. In this paper, the Pillar [5]arenes including ten and five quinoline units were synthesized and characterized by some procedures such as magnetic susceptibility, FT-IR, elemental analyses, 1H NMR, 13C NMR, melting point. Moreover, zinc(II) and copper (II) complexes were prepared to compare the antimicrobial effects with macrocyclic ligands. In the complex compounds, the metal:ligand ratios were determined with Job method as 1:2 and 1:1 for deca and penta units, respectively. The magnetic properties of the copper (II) complexes are 1.83 BM and 1.87 BM while zinc complexes have a diamagnetic character. The target macrocyclic ligands (Compound 7 and 8) and their metal complexes (Cu(II) and Zn(II)) were screened for the antimicrobial properties against the bacterial strains of Escherichia coli ATCC 25922, Staphylococcus aureus (MRSA) ATCC 43300, Klebsiella pneumoniae. ATCC 70603, Salmonella enteritidis ATTC 13076, Pseudomonas aeruginosa ATCC 27853, Bacillus cereus ATTC 11778, Sarcina lutea ATCC 9341, and yeast Candida albicans NRRL Y-417 by using broth microdilution method. Compound 7 has the optimum MIC values for S. aureus (MRSA), B. cereus, C. albicans and P. aeruginosa microorganisms that they were determined as 23.43, 46.87, 93.75 and 187 μg/mL, respectively. Moreover, Compound 8-Cu(II) complex was defined as an excellent antimicrobial agent against MRSA, B. cereus and C. albicans strains that the MIC values were determined as 3.9 μg/mL for both bacteria. The metal complexes of the target macrocyclic ligands have a more antimicrobial effect than the reactants and the target macrorings. Moreover, they have more successful results for Gram positive derivatives rather than Gram negative microorganisms.