Macrocyclic Ligand Research Articles

Design, synthesis, and pharmacological efficacy of sonication-irradiated nanostructured transition metal (II) designed macrocyclic complexes

The synthesis of transition metal (II) complexes from aspartic acid was accomplished by using sonication irradiation in this work. Sonication irradiation is a straightforward and efficient technique for synthesis. Physiological and spectroscopic studies were carried out to investigate the process of assembling nanostructured complexes. Using the serial dilution (2-fold) and free radical scavenging (DPPH) procedures, the antioxidant and antibacterial activity were assessed, respectively. Various bacteria, including Gram-positive and Gram-negative strains and fungi, were tested to determine the antimicrobial efficacies of the macrocyclic ligand and its accompanying metal complexes. The inhibitory results on microbes showed that metal complexes had more potent antibacterial effects than their Schiff base ligands. The findings demonstrated that the biological activity had a positive impact. Sonication irradiation of some complexes increased the movement of those complexes at concentrations ranging from 3.125 to 6.250 μg/ml (MIC). The Gaussian 09 software was utilized to simulate the three-dimensional structure of the complexes, the chemical reactivity of the produced macrocyclic ligand, and the binding energy of its complexes’ EHOMO and ELUMO energies using the B3LYP Density Functional Theory (DFT) method. This method is well-suited for pharmaceutical applications in the real world since it requires little effort to set up, produces a high yield, and requires a relatively small amount of solvent.

Luminescence properties of Eu3+ complexes based on macrocyclic ligands and its colorimetric analysis for white warm phosphor

Luminescence properties of Eu3+ complexes based on macrocyclic ligands and its colorimetric analysis for white warm phosphor

Dual-responsive solvatochromic sensor for simultaneous detection and mechanism of Cr(III) and Co(II) cations by a new N2O4-donor tetrabenzodiaza-crown ether Macrocyclic ligand anchored to dipyridine moieties

The present study describes the chemosensing capability of an N2O4-donor tetrabenzodiaza-crown ether macrocyclic ligand derivatized by two pyridine side arms to afford the flexible macrocyclic ligand, 5,20-bis(pyridin-4-ylmethyl)-5,6,12,13,19,20,26,27octahydrotetrabenzo [e,i,o,s][1,4,11,14]tetraoxa[7,18]diazacycloicosine (PMHBOA). A selective colorimetric behavior of PMHBOA for the prompt detection of Cr(ΙΙΙ) and Co(ΙΙ) can be observed with naked eyes. The 1H, 13C{H} NMR, and infrared spectroscopy disclosed the ligand binding capability for selective metal ions, ascribed to a 1:1 complex formation with Cr(III) and Co(II) cations in isopropanol. The limit of detection (LOD) values were calculated as 580 and 850 nM for Cr(ΙΙΙ) and Co(ΙΙ), respectively, accompanied with suitable LOQs as 1.95 µM for Cr(III) and 2.85 µM for Co(II), respectively. The reusability was confirmed in the presence of ethylenediaminetetraacetic acid (EDTA). Moreover, a TLC-based fabricated paper strip successfully applied PMHBOA as a chemosensor for synchronous visible detection of Cr(III) and Co(II) in their alcoholic solution. Meanwhile, the observed color change along with the turn-off fluorescent of PMHBOA guaranteed a felicitous choice of candidate for Cr(III) in the presence of other library metal ions in isopropanol:H2O (9/1 v/v) solution. A fast separation test on the filter paper, impregnated with PMHBOA, was also employed to separate Cr(III) and Co(II) cations from aqueous solutions by recording UV–vis spectra. The 1H NMR spectroscopy supported the macrocycle ring and side arms as the parallel coordination site of PMHBOA with Cr(III) and Co(II).

Direct and TEMPO‐Mediated Electro‐Oxidation of 5‐(Hydroxymethyl)furfural in Organic and Hydro‐Organic Media

AbstractBiomass‐derived 5‐hydroxymethyl furfural (5‐HMF) is a promising starting substrate for producing two high value‐added products 2,5‐diformylfuran (DFF) and 2,5‐furandicarboxylic acid (FDCA). DFF, which is produced by selectively oxidizing the hydroxymethyl group of 5‐HMF to an aldehyde group, has many applications in pharmaceuticals, macrocyclic ligands and fluorescent materials. Oxidizing both aldehyde and hydroxymethyl groups of 5‐HMF leads to FDCA, which is an important monomer in the production of a bioplastic polyethylene furanoate polymer. Electrochemical conversion of 5‐HMF is a potential route for sustainable chemical production of DFF and FDCA. In fact, using 2,2,6,6‐tetramethyl‐ piperidine‐1‐oxyl (TEMPO) as a redox mediator leads to a highly efficient and selective electro‐oxidation of 5‐HMF into FDCA in a basic buffer solution. In this report, the direct and TEMPO‐mediated electro‐oxidation of 5‐HMF was investigated in various organic and hydro‐organic media at room temperature. Direct electro‐oxidation leads to a low selective conversion of 5‐HMF to DFF (10 % of yield) and the formation of unwanted products such as formic acid and protoanemonin (90 % and 37 % of yield respectively) in acetonitrile. Electrocatalytic 5‐HMF conversion in the presence of TEMPO as a redox mediator achieved a near‐quantitative yield of DFF in acetonitrile and γ‐valerolactone. Importantly, we demonstrate the role of water in the conversion of aldehydes to carboxylic acids.

Identification, Characterization, and Electronic Structures of Interconvertible Cobalt-Oxygen TAML Intermediates.

The reaction of Li[(TAML)CoIII]·3H2O (TAML = tetraamido macrocyclic tetraanionic ligand) with iodosylbenzene at 253 K in acetone in the presence of redox-innocent metal ions (Sc(OTf)3 and Y(OTf)3) or triflic acid affords a blue species 1, which is converted reversibly to a green species 2 upon cooling to 193 K. The electronic structures of 1 and 2 have been determined by combining advanced spectroscopic techniques (X-band electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), X-ray absorption spectroscopy/extended X-ray absorption fine structure (XAS/EXAFS), and magnetic circular dichroism (MCD)) with ab initio theoretical studies. Complex 1 is best represented as an S = 1/2 [(Sol)(TAML•+)CoIII---OH(LA)]- species (LA = Lewis/Brønsted acid and Sol = solvent), where an S = 1 Co(III) center is antiferromagnetically coupled to S = 1/2 TAML•+, which represents a one-electron oxidized TAML ligand. In contrast, complex 2, also with an S = 1/2 ground state, is found to be multiconfigurational with contributions of both the resonance forms [(H-TAML)CoIV═O(LA)]- and [(H-TAML•+)CoIII═O(LA)]-; H-TAML and H-TAML•+ represent the protonated forms of TAML and TAML•+ ligands, respectively. Thus, the interconversion of 1 and 2 is associated with a LA-associated tautomerization event, whereby H+ shifts from the terminal -OH group to TAML•+ with the concomitant formation of a terminal cobalt-oxo species possessing both singlet (SCo = 0) Co(III) and doublet (SCo = 1/2) Co(IV) characters. The reactivities of 1 and 2 at different temperatures have been investigated in oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions to compare the activation enthalpies and entropies of 1 and 2.

Breaking a Molecular Scaling Relationship Using an Iron-Iron Fused Porphyrin Electrocatalyst for Oxygen Reduction.

The design of efficient electrocatalysts is limited by scaling relationships governing trade-offs between thermodynamic and kinetic performance metrics. This ″iron law″ of electrocatalysis arises from synthetic design strategies, where structural alterations to a catalyst must balance nucleophilic versus electrophilic character. Efforts to circumvent this fundamental impasse have focused on bioinspired applications of extended coordination spheres and charged sites proximal to a catalytic center. Herein, we report evidence for breaking a molecular scaling relationship involving electrocatalysis of the oxygen reduction reaction (ORR) by leveraging ligand design. We achieve this using a binuclear catalyst (a diiron porphyrin), featuring a macrocyclic ligand with extended electronic conjugation. This ligand motif delocalizes electrons across the molecular scaffold, improving the catalyst's nucleophilic and electrophilic character. As a result, our binuclear catalyst exhibits low overpotential and high catalytic turnover frequency, breaking the traditional trade-off between these two metrics.

A New Dy(III) Complex: Fluorescence Performances, Loading with Resveratrol-Hydrogels Against Skin Aging and Molecular Docking.

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

Synthesis, structural, multitargeted molecular docking analysis of anti-cancer, anti-tubercular, DNA interactions of benzotriazole based macrocyclic ligand

Biologically important macromolecule 1, 1′, 3, 3′ Bis − [2,3,5,6-Tetramethyl-p-phenylenebis(methylene)] dibenzotriazlinium dibromide hydrate (BTD) was synthesized and characterized using FT-IR, NMR and single-crystal XRD (SCXRD). SCXRD revealed that the compound was crystallized as a monoclinic system and associated through weak intermolecular interactions like H-bonding and π- π stacking interactions. These weak intermolecular interactions in BTD were studied using Crystal Explorer and Gaussian. The calculated energies for the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) showed the stability and reactivity of the title compound. Molecular electrostatic potential (MEP) surface analysis was used to investigate the crystal’s nucleophilic and electrophilic reactive sites. The molecular shape and intermolecular interactions in the crystal structure were determined using Hirshfeld surface analysis and fingerprint plots. Anticancer, anti-bacterial and DNA binding ability of BTD were investigated by experimental and theoretical techniques. The obtained results suggest that BTD possesses better anti-cancer, anti-bacterial and DNA binding abilities. The mode of action of antibiotic and anticancer approach was discussed. This provides promising therapeutic advantages for further development.

Synthesis, Isolation, and Study of Heterobimetallic Uranyl Crown Ether Complexes.

Although crown ethers can selectively bind many metal cations, little is known regarding the solution properties of crown ether complexes of the uranyl dication, UO22+. Here, the synthesis and characterization of isolable complexes in which the uranyl dication is bound in an 18-crown-6-like moiety are reported. A tailored macrocyclic ligand, templated with a Pt(II) center, captures UO22+ in the crown moiety, as demonstrated by results from single-crystal X-ray diffraction analysis. The U(V) oxidation state becomes accessible at a quite positive potential (E1/2) of -0.18 V vs Fc+/0 upon complexation, representing the most positive UVI/UV potential yet reported for the UO2n+ core. Isolation and characterization of the U(V) form of the crown complex are also reported here; there are no prior reports of reduced uranyl crown ether complexes, but U(V) is clearly stabilized by crown chelation. Joint computational studies show that the electronic structure of the U(V) form results in significant weakening of U-Ooxo bonding despite the quite positive reduction potential at which this species can be accessed, underscoring that crown-ligated uranyl species could demonstrate unique reactivity under only modestly reducing conditions.

Asparaginyl Endopeptidase-Mediated Peptide Cyclization for Phage Display.

We report here an enzymatic strategy for asparaginyl endopeptidase-mediated peptide cyclization. Incorporation of chloroacetyl groups into the recognition sequence of OaAEP1 enabled intramolecular cyclization with Cys residues. Combining this strategy and phage display, we identified nanomolar macrocyclic peptide ligands targeting TEAD4. One of the bicyclic peptides binds to TEAD4 with a KD value of 139 nM, 16 times lower than its linear analogue, demonstrating the utility of this platform in discovering high-affinity macrocyclic peptide ligands.

Binuclear Metal Phthalocyanines with Enhanced Activity in the Oxygen Evolution Reaction: A First-Principles Study.

The rational design of efficient catalysts for the electrochemical oxygen evolution reaction (OER) critically relies on a comprehensive understanding of the reaction mechanisms. Herein, the alkaline OER on planar mononuclear metal phthalocyanines (MPc, where M = Mn, Co, Fe, and Ni) and binuclear metal phthalocyanines (bi-MPc) is studied using density functional theory (DFT) methods. Both FePc and bi-CoPc exhibit enhanced stability and OER activity, with the energy required for the leaching of central metal being as high as 2.28 and 2.45 eV and the overpotentials of the OER being 0.48 and 0.57 V, respectively. Through electronic structure analysis, it is found that, in the OER process of bi-MPc, the large macrocyclic ligand and metal ions not bonding with the intermediate can serve as hole reservoirs. Intermediate species are further stabilized by the dispersal of a positive charge, reducing the free energy. These findings underscore the significance of macrocyclic ligands in the rate-determining step of the OER catalyst.

Recent Advances in Non‐Standard Macrocyclic Peptide Ligand Discovery using mRNA Display

AbstractAdvancements in platform technologies have facilitated the production of libraries consisting of macrocyclic peptides composed of natural and non‐canonical amino acids for more drug‐like characteristics. Identification of macrocyclic peptide ligands against targets of interest can be accomplished using mRNA display. Despite numerous successful in vitro selections for macrocyclic peptide ligands against extracellular targets, identifying macrocyclic peptide hits that can reach intracellular targets continue to be a challenge. Breakthroughs in defining the features of a macrocyclic peptide that promote cell permeability have recently been disclosed. Here, we review the successful selections of non‐standard macrocyclic peptide ligands using mRNA display in the last five years and chemical optimization of a drug‐like macrocyclic peptide ligand for targeting intracellular KRAS.

Spectroscopic Rationalization of Selective Colorimetric Chemosensing of Fe(lll) in Aqueous Medium by a New Mono-Substituted Dibenzodiaza-Crown Ether Macrocyclic Ligand Appended with Mono 2-Benzimidazole N-Pendant Side Arm.

Optical chemosensor L comprising of a new mono-N-substituted derivative of dibenzodiaza-crown ether macrocyclic ligand bearing a 2-benzimidazole (2Bim) side arm was synthesized, and characterized by FT-IR, elemental microanalyses, 1H NMR, and 13C NMR, UV-visible, fluorescence (FL) spectroscopy. The colorimetric chemosensing behavior of L toward the library metal ions was examined, wherein L represented a prompt and selective yellow-to-purple color change for Fe(III) cation in a 25µM solution with LOD as 0.23 µM in ethanol:water (9:1, v/v), even in the presence of the other library metal ions (LMI). Based on the 1H NMR, UV-visible, and FL observations the coordination sphere of Fe(III) was shared with two 2-benzoimidazole (2Bim) side arms which were also confirmed by the elemental microanalyses (in the solid state) and the Job plot method (in the solution) of the complex. Moreover, the above-mentioned color change was attributed to the presence of a strong charge transfer (LMCT) band for the Fe(III)/L interaction in the solution. Furthermore, the viscosity measurement in the presence of Fe(III) uncovered an increase at 0.5-1.0 ratios for Fe(III)/L, attributable to the formation of a self-assembly in the solution. A TLC paper strip was impregnated by L for selective detection of Fe(III), demonstrating a live color change for Fe(III) at 0-5 mM in the presence of LMI.

Current Development of Lanthanide Complexes for Biomedical Applications.

Luminescent molecule-based bioimaging system is widely used for precise localization and distinction of cancer/tumor cells. Luminescent lanthanide (Ln(III)) complexes offer long-lived (sub-millisecond time scale) and sharp (FWHM <10 nm) emission, arising from the forbidden 4f-4f electronic transitions. Luminescent Ln(III) complex-based bioimaging has emerged as a promising option for both in vitro and in vivo visualizations. In this mini-review, the historical development and recent significant progress of luminescent Ln(III) probes for bioapplications are introduced. The recent studies are mainly focused on three points: (i) the structural modifications of Ln(III) complexes in both macrocyclic and small ligands, (ii) the acquirement of high resolution luminescence images of cancer/tumor cells and (iii) the constructions of ratiometric biosensors. Furthermore, our recent study is explained as a new Cancer GPS (cancer grade probing for determining tumor grade through photophysical property analyses of intracellular Eu(III) complex.

Design, synthesis, characterization, in vitro cytotoxic, antimicrobial, antioxidant studies, DFT, thermal and molecular docking evaluation of biocompatible Co(II) complexes of N4O4-macrocyclic ligands

Bioactive cobalt (II) macrocyclic complexes [Co(N4O4ML1)Cl2]-[Co(N4O4ML3)Cl2] have been synthesized by using the macrocyclic ligands [N4O4ML1], [N4O4ML2], and [N4O4ML3] that have an N4O4 core. These three macrocyclic ligands were all isolated in pure form, together with their complexes. Microanalytical investigations, FT-IR NMR, Mass, magnetic moments, electronic, PXRD, TGA, and EPR spectrum studies were used to analyse their structures. For these complexes, an octahedral geometry is proposed for the metal ion. By using molecular weights and conductivity measurements the monomeric and non-electrolytic nature has been confirmed. The Coats-Redfern and FWO methods are used to determine the thermodynamic characteristics of the ligands and their Co(II) complexes. The molecular modelling using the DFT technique displays the bond angle, bond lengths and quantum chemical properties. To determine their ability to prevent the growth of harmful fungus and bacteria, the ligands [N4O4ML1]- [N4O4ML3] 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(N4O4ML3)Cl2] antioxidative capabilities revealed significant radical scavenging power. The MTT assay was used to assess the toxicity of all the synthesised compounds under inquiry on MCF-7, HeLa, and A549 cancer cells. The findings revealed that the ligand and the compounds gave outstanding IC50 values in the range of 9.07–36.25 (uM) at a concentration of 25 ppm. Among all the substances evaluated, [Co(N4O4ML3)Cl2] complex was discovered to be the most active and least cytotoxic. Additionally, docking investigations of the produced compounds were carried out in order to validate the biological outcomes.

Ein modifiziertes Ankerpeptid LCI mit einem Cobalt‐Cofaktor verbessert die Oxidationseffizienz von Polystyrol‐Mikropartikeln

AbstractEin typischer Bestandteil von Polymerabfällen ist Polystyrol (PS), das in zahlreichen Anwendungen eingesetzt wird, aufgrund seiner hydrophoben Eigenschaften in der Umwelt aber nur langsam abgebaut wird. Um die Reaktivität von Polystyrol zu erhöhen, müssen polare Gruppen eingeführt werden. In dieser Arbeit werden biohybride Katalysatoren auf Grundlage des modifizerten Ankerpeptids LCI_F16C vorgestellt, die sich an Polystyrol‐Mikropartikel anheften können und benzylische C−H‐Bindungen in Polystyrol‐Mikropartikeln mit handelsüblichem Oxon als Oxidationsmittel hydroxylieren. Eine dichte Oberflächenbedeckung von PS mit LCI‐Peptid erfolgt durch Bildung von Monoschichten innerhalb von Minuten in wässrigen Lösungen bei Raumtemperatur. Der katalytisch aktive Cobalt‐Cofaktor Co‐L1 oder Co‐L2 mit einem modifizierten NNNN‐makrozyklischen TACD‐Liganden (TACD=1,4,7,10‐Tetraazacyclododecan) ist über einen Maleimid‐Linker kovalent an das Ankerpeptid LCI gebunden. Im Vergleich zu den freien Cofaktoren wurde eine 12‐ bis 15‐fache Verbesserung der katalytischen Aktivität mit Biohybrid‐Katalysatoren auf Basis von LCI_F16C beobachtet.

Engineered Anchor Peptide LCI with a Cobalt Cofactor Enhances Oxidation Efficiency of Polystyrene Microparticles.

A typical component of polymer waste is polystyrene (PS) used in numerous applications, but degraded only slowly in the environment due to its hydrophobic properties. To increase the reactivity of polystyrene, polar groups need to be introduced. Here, biohybrid catalysts based on the engineered anchor peptide LCI_F16C are presented, which are capable of attaching to polystyrene microparticles and hydroxylating benzylic C-H bonds in polystyrene microparticles using commercially available oxone as oxidant. LCI peptides achieve a dense surface coverage of PS through monolayer formation within minutes in aqueous solutions at ambient temperature. The catalytically active cobalt cofactor Co-L1 or Co-L2 with a modified NNNN macrocyclic TACD ligand (TACD=1,4,7,10-tetraazacyclododecane) is covalently bound to the anchor peptide LCI through a maleimide linker. Compared to the free cofactors, a 12- to 15-fold improvement in catalytic activity using biohybrid catalysts based on LCI_F16C was observed.

Comprehensive Photophysical and Nonlinear Spectroscopic Study of Thioanisolyl‐Picolinate Triazacyclononane Lanthanide Complexes

AbstractDetailed photophysical studies of luminescent lanthanide complexes are presented and elaborated using a newly developed thioanisolyl‐picolinate antenna and the related tacn macrocyclic ligand. The new ligand proved to sensitise Nd(III), Sm(III), Eu(III) and Yb(III) emission. Eu(III) complex showed complete energy transfer, yielding high quantum yield (44 %) and brightness, while the Tb(III) analogue underwent a thermally activated back‐energy transfer, resulting in a strong oxygen quenching of the triplet excited state. Transient absorption spectroscopy measurements of Gd(III), Tb(III) and Eu(III) compounds confirmed the sensitization processes upon the charge‐transfer antenna excitation. The triplet excited state lifetime of the Tb(III) complex was 5‐times longer than that of the Gd(III) analogue. In contrast, the triplet state was totally quenched by the energy transfer to the 4f‐metal ion in the Eu(III) species. Nonlinear two‐photon absorption highlighted efficient biphotonic sensitization in Eu(III) and Sm(III) complexes. In case of the Nd(III) compound, one‐photon absorption in 4f–4f transitions was predominant, despite the excitation at the antenna two‐photon band. This phenomenon was due to the Nd(III) 4f–4f transitions overlapping with the wavelength‐doubled absorption of the complex.

Metal–N4 model single‐atom catalyst with electroneutral quadri‐pyridine macrocyclic ligand for CO2 electroreduction

AbstractMetal–N–C single‐atom catalysts, mostly prepared from pyrolysis of metal‐organic precursors, are widely used in heterogeneous electrocatalysis. Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure, a reliable structure–property relationship is difficult to establish. Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the single‐atom catalysts. Metal–N4 site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts, but its molecular counterpart has not been reported. In this work, we synthesized the conjugated macrocyclic complexes with a metal center (Co, Fe, or Ni) coordinated with four electroneutral pyridinic ligands as model catalysts for CO2 electroreduction. For comparison, the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared. The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand. Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO2.

Macrocyclic Sulfur Ligand Stabilized Trans-Palladium Dichloride Complex: Syntheses, Structure, Chlorine Rotation, and Application in α-Olefination of Nitriles by Primary Alcohols.

Herein, we have reported the synthesis of a macrocyclic organosulfur ligand (L1) having a seventeen-membered macrocyclic ring. Subsequently, the corresponding trans-palladium complex (C1) of bulky macrocyclic organosulfur ligand (L1) was synthesized by reacting it with PdCl2 (CH3 CN)2 salt. The newly synthesized ligand and complex were characterized using various analytical and spectroscopic techniques. The complex showed a square planar geometry with trans orientation of two ligands around the palladium center. The complex possesses intramolecular SCH…Cl interactions of 2.648 Å between the macrocyclic ligand and palladium dichloride. The potential energy surface (PES) for the rotational process of C1 suggested a barrier of ~23.81 kcal/mol for chlorine rotation. Furthermore, the bulky macrocyclic organosulfur ligand stabilized palladium complex (C1) was used as a catalyst (2.5 mol %) for α-olefination of nitriles by primary alcohols. The α,β-unsaturated nitrile compounds were found to be the major product of the reaction (57-78 % yield) with broad substrate scope and large functional group tolerance. Notably, the saturated nitrile product was not observed during the reaction. The mechanistic studies suggested the formation of H2 and H2 O as only by-products of the reaction, thereby making the protocol greener and sustainable.