Ligand Functional Groups Research Articles

Mechanism for airborne ozone decomposition on X-MIL-53(Fe) (X = H, NH2, NO2)

Ground−level ozone (O3) pollution poses a significant threat to both ecosystem sustainability and human health. The catalytic decomposition of O3 presents as a promising technology to address the issues of O3 pollution. This study undertook the synthesis of various functionalized metal−organic framework (MOF) catalysts (i.e., X-MIL-53(Fe) (X = H, NH2, NO3)) to delve into the influence of ligand functional groups on skeletal structure and catalytic efficacy, particularly focusing on unraveling the mechanism of O3 catalytic decomposition under humid conditions. NH2-MIL-53(Fe) catalyst achieved complete O3 decomposition under ambient temperature and high humidity conditions (RH=75 %), exhibiting a reaction rates (mol·m−2·s−1) 129 and 10.5 times greater than that of MIL-53(Fe) and NO2-MIL-53(Fe). The NH2 group promotes electron flow within the backbone towards the hydroxyl group (OH) linked to Fe atom. In humid O3, H2O molecules augment the interaction between O3 and NH2-MIL-53(Fe), and OH is converted to·O2− after deprotonation, promoting O3 decomposition. Additionally, leveraging three−dimensional (3D) printing technology, a monolithic catalyst for O3 decomposition was prepared for application. This study not only advances understanding of the mechanisms underlying O3 decomposition but also offers practical solutions for addressing O3 pollution at humid conditions.

Halogenated 2,4-diphenyl indeno[1,2-B]pyridinol derivatives as potential inhibitors of the androgen receptor (PDB ID: 58TE): A study of QSAR modeling, molecular docking, and pharmacokinetics for prostate cancer treatment

The present research was centered on the development of a predictive model aimed at assessing the responses of prostate tumors to a range of compounds within the scope of the pIC50 project. Our approach involved the utilization of a quantitative structure-activity relationship (QSAR) methodology, incorporating a genetic algorithm (GA) and multiple linear regression analyses (MLRA) applied to a dataset comprising 128 derivatives. The resultant model demonstrated a robust predictive capacity, supported by Remarkable internal and external validation metrics (R² = 0.9143 for internal consistency and R²ext. = 0.9523 for external validation), thus indicating its reliability in prognosis of tumor responses. Additionally, molecular docking simulations yielded valuable insights into the interactions between the ligands and target proteins, highlighting the significance of specific amino acid residues in the binding mechanism. These interactions were characterized by hydrogen bonds, halogen bonds, and pi-cation interactions, pointing to a substantial binding affinity with a score of −10.9 kJ/mol. The comprehensive molecular understanding obtained, including the critical role of ligand functional groups in determining interaction types, pointing out the utility of the model in identifying potential therapeutic agents. Furthermore, the study highlighted the modulation of the androgen receptor as an essential target in the treatment of prostate cancer. Molecular docking highlighted important interactions that can inform the design of novel anti-prostate cancer agents. Through the application of GA-MLR techniques, the study not only confirmed the efficacy of the predictive model in understanding prostate cancer responses but also showcased the potential of QSAR modeling in advancing prostate cancer research. The outcomes furnish a solid basis for further exploration of therapeutic compounds, emphasizing the intricate interplay between molecular structure and biological activity in the domain of drug development.

Ag-MOF Nanocatalyst for the Asymmetric Hantzsch Synthesis of Polyhydroquinolines Under Green Conditions

A highly efficient and stable heterogeneous coordination polymer (CP) catalyst was successfully prepared by hydrothermal reaction of silver and 4,6-Diamino-2-pyrimidinethiol, using amine, thiol and pyrimidine functional groups. Besides, silver ions were coordinated to the ligand functional groups in order to give a novel Ag-CPs catalyst. Besides, it was characterized using FT-IR, XRD, TGA, SEM, EDX, X-ray mapping and BET analysis. The prepared Ag-CPs exhibit excellent catalytic activity for multicomponent Hantzsch synthesis of polyhydroquinolines under mild reaction condition in relatively short reaction times. The heterogeneity of the catalyst was confirmed by the hot filtration test and, then, the catalyst was reused for at least four times under the optimized conditions without any significant loss of its activity.

Synthesis, Spectroscopic Characterization, DFT, Molecular Docking, Catechol Oxidase Activity, and Anti-SARS-CoV-2 of Acylhydrazone Derivatives

In the present work, five pyrazole-hydrazone biomolecule ligands (L1–L5) were synthesized by condensation between 1H-pyrazole-3-carbohydrazide (2) and aromatic benzaldehydes. Their corresponding structures were elucidated employing NMR and FT-IR spectra and ESI-MS data. Li-Cu(II) complexes (i = 1–5) were evaluated for catecholase activity in situ at standard conditions. The findings disclose that the catecholase oxidation rate varies with the substituted functional groups in ligand and the anion type in the copper (II) salt. Catecholase activity results showed that the L(i = 1–5) -Cu(II)SO4 complexes exhibited efficient catalytic activity, and a maximum activity of 105 ± 42 µM.min−1 is obtained with L5-Cu(II)SO4. DFT and NBO calculations have been carried out to identify the global reactivity and the strength of interaction bonds between the donors and acceptors in L1–L5. The optimized structure of L1–L3 and L5 were found planar, while that of L4 is out of the molecular plan and forms a torsion angle of 18 degrees due to the presence of methoxy and hydroxyl group at meta and para. In L4, the 5-methyl-1H-pyrazole moiety. NBO findings show that the strongest interactions in L1–L5 are those involved in the electronic transition from π-bonding → π*-antibonding and LP → π*- antibonding molecular orbitals. Further, the anti-SARS-CoV-2 of L1–L5 are investigated by estimating their binding affinities into its binding. The docking results reveal that L1–L5 may act as SARS-CoV-2 main protease inhibitors with estimated binding energies in the −6.00 to −8.0 kcal.mol−1 range.

Enabling long-distance hydrogen spillover in nonreducible metal-organic frameworks for catalytic reaction

Hydrogen spillover is an extraordinary effect in heterogeneous catalysis and hydrogen storage, which refers to the surface migration of metal particle-activated hydrogen atoms over the solid supports. Historical studies on this phenomenon have mostly been limited to reducible metal oxides where the long-distance proton-electron coupled migration mechanism has been established, yet the key question remains on how to surmount short-distance and defect-dependent hydrogen migration on nonreducible supports. By demerging hydrogen migration and hydrogenation reaction, here we demonstrate that the hydrogen spillover in nonreducible metal-organic frameworks (MOFs) can be finely modulated by the ligand functional groups or embedded water molecules, enabling significant long-distance (exceed 50 nm) movement of activated hydrogen. Furthermore, using sandwich nanostructured MOFs@Pt@MOFs as catalysts, we achieve highly selective hydrogenation of N-heteroarenes via controllable hydrogen spillover from Pt to MOFs-shell. We anticipate that this work will enhance the understanding of hydrogen spillover and shed light on de novo design of MOFs supported catalysts for many important reactions involving hydrogen.

Influence of ligands as chemical admixtures in the early hydration of sodium carbonate-activated blast furnace slag

Insufficient strength performance at early age impedes the use of sodium carbonate (SC) activator to produce sustainable blast furnace slag-based binders. To solve this issue, this study aimed to accelerate the early hydration kinetics of SC-activated slag system using ligand admixtures: triethanolamine (TEA), triisopropanolamine (TIPA), trisodium nitrilotriacetate (NTA), tetra potassium pyrophosphate (TKPP), and 2,3-dihydroxynapthalene (DHNP). Effect of ligands were investigated by isothermal calorimetry, compressive strength determinations, workability tests, XRD analysis, TGA, and batch dissolution tests. Results showed that the effect of the ligand on the reaction mechanism and strength development depends on the ligand functional group, concentration, and dissolution and metal complexing properties. Between the investigated ligands, 25 mM of DHNP accelerated the hydration kinetics by 28 h and produced 2-day strength of 41 MPa compared to the reference of only 2 MPa. Mechanism behind this acceleration is by affecting the ion activity product (IAP) of layered double hydroxides (LDHs) or C-(A)-S-H phases and not hindering the underlying carbonate salts (gaylussite, calcite) precipitation kinetics. These findings show the potential of ligands as admixtures in binder forming reactions and holds the key to potentially develop and fine tune sustainable low-CO2 binders.

Prediction of Binding Pose and Affinity of Nelfinavir, a SARS-CoV-2 Main Protease Repositioned Drug, by Combining Docking, Molecular Dynamics, and Fragment Molecular Orbital Calculations.

A novel in silico drug design procedure is described targeting the Main protease (Mpro) of the SARS-CoV-2 virus. The procedure combines molecular docking, molecular dynamics (MD), and fragment molecular orbital (FMO) calculations. The binding structure and properties of Mpro were predicted for Nelfinavir (NFV), which had been identified as a candidate compound through drug repositioning, targeting Mpro. Several poses of the Mpro and NFV complexes were generated by docking, from which four docking poses were selected by scoring with FMO energy. Then, each pose was subjected to MD simulation, 100 snapshot structures were sampled from each of the generated MD trajectories, and the structures were evaluated by FMO calculations to rank the pose based on binding energy. Several residues were found to be important in ligand recognition, including Glu47, Asp48, Glu166, Asp187, and Gln189, all of which interacted strongly with NFV. Asn142 is presumably regarded to form hydrogen bonds or CH/π interaction with NFV; however, in the present calculation, their interactions were transient. Moreover, the tert-butyl group of NFV had no interaction with Mpro. Identifying such strong and weak interactions provides candidates for maintaining and substituting ligand functional groups and important suggestions for drug discovery using drug repositioning. Besides the interaction between NFV and the amino acid residues of Mpro, the desolvation effect of the binding pocket also affected the ranking order. A similar procedure of drug design was applied to Lopinavir, and the calculated interaction energy and experimental inhibitory activity value trends were consistent. Our approach provides a new guideline for structure-based drug design starting from a candidate compound whose complex crystal structure has not been obtained.

A copper(II) aminopyrimidinone complex: X-ray crystallography, computational analysis, dielectric spectroscopy and molecular docking

A new copper(II) complex with 2-amino-6-methylpyrimidin-4-(1H)-one, [Cu(C5H7N3O)4](NO3)2·H2O (Cupyrim), has been synthesized and studied by X-ray diffraction, elemental analysis and FT-IR spectroscopy. The Cu(II) is four-coordinate in a square planar geometry by four nitrogen atoms of the four organic ligands. Hirshfeld Surface Analysis was conducted to understand crystalline packing. Overall, the structure is maintained by metal coordination as well as strong and weak (C,N)–H···O hydrogen bonds and C–H…π interactions. The IR spectrum primary peaks have been assigned to the vibration modes of the ligand functional groups. An investigation of the inhibitory properties of Cupyrim toward “Cyclin-dependent Kinase 2” (CdK2) and “inducible nitric oxide synthase” (iNOS) proteins was aided by molecular docking research. According to molecular docking, Cupyrim exhibits promising inhibitory efficacy against Parkinson’s, schizophrenia, and Alzheimer’s disorders. The temperature dependence of the real and imaginary part of the dielectric permittivity was analyzed with the Cole-Cole formalism as well as DSC diagrams from 45-147 °C.

Manipulating the structure and oxygen evolution reaction performance in metal organic frameworks via symmetrical control on the functional groups of ligands

The crystal structure and electrocatalytic performance of Ni-based MOFs were controlled by the symmetrical engineering of Br functional groups on the terephthalic acid ligand.

Rapid nucleation and optimal surface-ligand interaction stabilize wurtzite MnSe.

Non-native structures (NNS) differ in discrete translational symmetry from the bulk ground state native structure (NS). To explore the extent of deconvolution of various factors relevant to the stabilization of the wurtzite/NNS of MnSe via a heat-up method, we performed experiments using various ligands (oleic acid, oleylamine, octadecylamine, stearic acid, and octadecene), solvents (tetraethylene glycol and octadecene), and precursor salts (manganese chloride and manganese acetate). Experiments suggest that oleic acid in the presence of tetraethylene glycol and oleylamine in the presence of octadecene stabilize wurtzite/NNS. Further, density functional theory (DFT) computations explore the interaction between the functional groups in ligands and the most exposed surfaces of wurtzite/NNS and rocksalt/NS polymorphs. Computations suggest that the interactions between relevant surface facets with carboxylic acid and the double bond functional groups suppress the phase transformation from NNS to NS. In addition, the ionizability of the precursor salt also determines the rate of formation of the metal-ligand complex and the rate of nucleation. Consequently, the formation rate of the Mn-ligand complex is expected to be greater in the case of chloride salt than acetate salt because the chloride salt has higher ionizability in ethylene glycol. From the above, we conclude that the kinetics of the wurtzite/NNS to rocksalt/NS phase transformation depends mainly on two factors: (1) nucleation/growth kinetics which is controlled by the ionizability of the precursor salt, solvent, and stability of the metal-ligand complex, and (2) the activation energy barrier of the NNS to NS conversion which is controlled by surface energy minimization with the ligand.

(Invited) Highly Emissive CdTe Quantum Dots Passivated with Novel Branched Ligands as Fluorescent Sensors

Fluorescent-based sensors attract enormous attention due to their facile nature, simplicity, superior selectivity and sensitivity, and better reproducibility and reliability. The sensing parameters, such as detection limit, dynamic range, and the possibility for multiplexed detection, rely hugely on the physicochemical properties of the fluorophore used. Therefore, the choice and rational design of fluorescent probes demand considerable attention. The growing interest in highly fluorescent semiconductor quantum dots as sensors or imaging probes is evident from the numerous reports available in the literature. Unlike conventional organic dyes, novel fluorescent quantum dots-inorganic nanocrystals have manifold advantages. QDs have symmetric and narrow emission profiles, high absorption efficiency in the UV region, high quantum yields, especially in the NIR region, exorbitant photo and temporal stability, and shallow photo-bleaching effect. The optical properties of QDs are primarily defined by the nature of constituent materials, size and shape, surface chemistry, and the nature of dangling bonds. The applicability of CdTe QDs was limited in the biological realm mainly due to the highly toxic nature of its constituent materials. The use of benign ligands is one procedure to be adopted to overcome this impediment. Also, the stability of the QDs warrants the limited bleaching of the material. The aqueous solubility of the material is another requirement to be satisfied. The functional groups in ligands also play a significant role in determining the stability of QDs and the utility of the QDs synthesized, as it can advocate the possibility of reactions and recognition of suitable analytes in sensing schemes. This talk will discuss the choice of organic ligands with side methyl chains that can supplement or be used in alternatives to the existing ligands for synthesizing QDs. We have employed easy and facile colloidal synthetic procedures for an extended period for manipulating the size of QDs formed, which can be further implemented for the sensing of various analytes. The side methyl chain added several benefits for the QDs synthesis, such as providing better stability of the QDs and in the sensing scenario.

Chemical features and machine learning assisted predictions of protein-ligand short hydrogen bonds

There are continuous efforts to elucidate the structure and biological functions of short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms reside more than 0.3 Å closer than the sum of their van der Waals radii. In this work, we evaluate 1070 atomic-resolution protein structures and characterize the common chemical features of SHBs formed between the side chains of amino acids and small molecule ligands. We then develop a machine learning assisted prediction of protein-ligand SHBs (MAPSHB-Ligand) model and reveal that the types of amino acids and ligand functional groups as well as the sequence of neighboring residues are essential factors that determine the class of protein-ligand hydrogen bonds. The MAPSHB-Ligand model and its implementation on our web server enable the effective identification of protein-ligand SHBs in proteins, which will facilitate the design of biomolecules and ligands that exploit these close contacts for enhanced functions.

A General One-Step Synthesis of Alkanethiyl-Stabilized Gold Nanoparticles with Control over Core Size and Monolayer Functionality.

In spite of widespread interest in the unique size-dependent properties and consequent applications of gold nanoparticles (AuNPs), synthetic protocols that reliably allow for independent tuning of surface chemistry and core size, the two critical determinants of AuNP properties, remain limited. Often, core size is inherently affected by the ligand structure in an unpredictable fashion. Functionalized ligands are commonly introduced using postsynthesis exchange procedures, which can be inefficient and operationally delicate. Here, we report a one-step protocol for preparing monolayer-stabilized AuNPs that is compatible with a wide range of ligand functional groups and also allows for the systematic control of core size. In a single-phase reaction using the mild reducing agent tert-butylamine borane, AuNPs that are compatible with solvents spanning a wide range of polarities from toluene to water can be produced without damaging reactive chemical functionalities within the small-molecule surface-stabilizing ligands. We demonstrate that the rate of reduction, which is easily controlled by adjusting the period over which the reducing agent is added, is a simple parameter that can be used irrespective of the ligand structure to adjust the core size of AuNPs without broadening the size distribution. Core sizes in the range of 2-10 nm can thus be generated. The upper size limit appears to be determined by the nature of each specific ligand/solvent pairing. This protocol produces high quality, functionally sophisticated nanoparticles in a single step. By combining the ability to vary size-related nanoparticle properties with the option to incorporate reactive functional groups at the nanoparticle-solvent interface, it is possible to generate chemically reactive colloidal building blocks from which more complex nanoparticle-based devices and materials may subsequently be constructed.

The Chemistry of the Cyaphide Ion.

We review the known chemistry of the cyaphide ion, (C≡P)- . This remarkable diatomic anion has been the subject of study since the late nineteenth century, however its isolation and characterization eluded chemists for almost a hundred years. In this mini-review, we explore the pioneering synthetic experiments that first allowed for its isolation, as well as more recent developments demonstrating that cyaphide transfer is viable in well-established salt-metathesis protocols. The physical properties of the cyaphide ion are also explored in depth, allowing us to compare and contrast the chemistry of this ion with that of its lighter congener cyanide (an archetypal strong field ligand and important organic functional group). Recent studies show that the cyaphide ion has the potential to be used as a versatile chemical regent for the synthesis of novel molecules and materials, hinting at many interesting future avenues of investigation.

Fluorescent Probes Based on Metal and Aggregation-induced Luminescent Organic Molecule Complexes for Bioimaging and Sensing Applications

Metal-Organic Coordination polymer (MOCPs) is an emerging class of inorganic-organic porous hybrid materials with infinite coordination polymers (CPs) or metal-organic backbones (MOFs) formed by the interaction between metal ions and organic ligands and ligand functional groups. The molecular structure of the organic ligands composing MOCPs is rich in variation, while inorganic metal ions generally have good photoelectromagnetic properties. Therefore, MOCPs have diverse structural variations, adjustable pore size, high stability and controllable synthesis, and have received wide attention in gas storage, multiphase catalysis, chemical sensing and biological applications. Fluorescence properties are one of the most widely used techniques for bioimaging and sensing detection. However, conventional luminescent groups are usually affected by aggregation-induced quenching (ACQ) effects. Aggregation-induced luminescence molecules (AIEs) based on metal-organic coordination polymers combine the advantages of organic AIEs and transition metal centers to improve photophysical properties and therapeutic effects.

Quantum Mechanical Assessment of Protein-Ligand Hydrogen Bond Strength Patterns: Insights from Semiempirical Tight-Binding and Local Vibrational Mode Theory.

Hydrogen bonds (HB)s are the most abundant motifs in biological systems. They play a key role in determining protein-ligand binding affinity and selectivity. We designed two pharmaceutically beneficial HB databases, database A including ca. 12,000 protein-ligand complexes with ca. 22,000 HBs and their geometries, and database B including ca. 400 protein-ligand complexes with ca. 2200 HBs, their geometries, and bond strengths determined via our local vibrational mode analysis. We identified seven major HB patterns, which can be utilized as a de novo QSAR model to predict the binding affinity for a specific protein-ligand complex. Glycine was reported as the most abundant amino acid residue in both donor and acceptor profiles, and N-H⋯O was the most frequent HB type found in database A. HBs were preferred to be in the linear range, and linear HBs were identified as the strongest. HBs with HB angles in the range of 100-110°, typically forming intramolecular five-membered ring structures, showed good hydrophobic properties and membrane permeability. Utilizing database B, we found a generalized Badger's relationship for more than 2200 protein-ligand HBs. In addition, the strength and occurrence maps between each amino acid residue and ligand functional groups open an attractive possibility for a novel drug-design approach and for determining drug selectivity and affinity, and they can also serve as an important tool for the hit-to-lead process.

Ligand Tailoring and Functional Group Fusion Strategy for Developing Photochromic Compounds: A Case Study for Pyridinedicarboxylic Acid

Hybrid photochromic materials (HPMs) can produce novel photoresponsive properties, thanks to the synergistic effect of each component. One of the widely explored ways toward a novel HPM system is the utilization of the phototriggered electron transfer (ET) mechanism. In this work, the photochromic functionality of pyridinedicarboxylic acid with the chemical formula of H2-L1·H2O (1, H2-L1 = 2,6-pyridinedicarboxylic acid) and related metal–organic complexes (MOCs), [Zn(HL1)2]·2.5H2O (2), [Pb(L2)] (3, H2-L2 = 2,4-pyridinedicarboxylic acid), [In(L2)(HL2)]·2H2O (4), and [Eu3(L2)4(OH)(H2O)2]·11H2O (5), has been first proved via the ligand tailoring and functional group fusion strategy. The photogenerated radicals derived from ET were experimentally characterized. Different from the previously investigated HPMs based on electron-deficient pyridiniums and rigid polydentate N-ligands as electron acceptors (EAs), this work exploits a new category of ligands for developing HPMs and investigating the underlying photoresponsive functionalities. Considering the large varieties of carboxylate and pyridine moieties, this study offers a general strategy for developing new HPMs and exploring the potential photoresponsive functionality via integrating the carboxylic groups as electron donors (EDs) and pyridyl groups as EAs in the single ligand.

Recent Advances in Transition Metal-Based Catalysts for Ethylene Copolymerization with Polar Comonomer.

The synthesis of polar functionalized polyolefin (PFP) offers improvement in mixing properties, polymer surface, and rheological properties with the potential of upgraded polyolefins for modern and ingenious applications. The synthesis of PFP from metal-based catalyzed olefin (non-polar in nature) copolymerization with polar comonomers embodies energy-efficient, atom-efficient, and apparently an upfront methodology. Despite their outstanding success during conventional polymerization of olefin, 3rd and 4th group (early transition metal)-based catalysts, owing to their electrophilic nature, face challenges mainly due to Lewis basic sites of the polar monomers. On the contrary, late transition metal-based catalysts have also made progress, in recent years, for PFP synthesis. The recent past has also witnessed several advancements in the development of dominating palladium-based catalysts while their lower resistance towards ligand functional groups has limited the practical application of abundant and cheaper nickel-based catalysts. However, the relentless efforts of the scientific community, during the past half-decade, have indicated rigorous progress in the development of nickel-based catalysts for PFP synthesis. In this review, we have abridged the recent research trends in both early as well as late transition metal-based catalyst development. Furthermore, we have highlighted the role of transition metal-based catalysts in influencing the polymer properties.

Precision nanoengineering for functional self-assemblies across length scales.

As nanotechnology continues to push the boundaries across disciplines, there is an increasing need for engineering nanomaterials with atomic-level precision for self-assembly across length scales, i.e., from the nanoscale to the macroscale. Although molecular self-assembly allows atomic precision, extending it beyond certain length scales presents a challenge. Therefore, the attention has turned to size and shape-controlled metal nanoparticles as building blocks for multifunctional colloidal self-assemblies. However, traditionally, metal nanoparticles suffer from polydispersity, uncontrolled aggregation, and inhomogeneous ligand distribution, resulting in heterogeneous end products. In this feature article, I will discuss how virus capsids provide clues for designing subunit-based, precise, efficient, and error-free self-assembly of colloidal molecules. The atomically precise nanoscale proteinic subunits of capsids display rigidity (conformational and structural) and patchy distribution of interacting sites. Recent experimental evidence suggests that atomically precise noble metal nanoclusters display an anisotropic distribution of ligands and patchy ligand bundles. This enables symmetry breaking, consequently offering a facile route for two-dimensional colloidal crystals, bilayers, and elastic monolayer membranes. Furthermore, inter-nanocluster interactions mediated via the ligand functional groups are versatile, offering routes for discrete supracolloidal capsids, composite cages, toroids, and macroscopic hierarchically porous frameworks. Therefore, engineered nanoparticles with atomically precise structures have the potential to overcome the limitations of molecular self-assembly and large colloidal particles. Self-assembly allows the emergence of new optical properties, mechanical strength, photothermal stability, catalytic efficiency, quantum yield, and biological properties. The self-assembled structures allow reproducible optoelectronic properties, mechanical performance, and accurate sensing. More importantly, the intrinsic properties of individual nanoclusters are retained across length scales. The atomically precise nanoparticles offer enormous potential for next-generation functional materials, optoelectronics, precision sensors, and photonic devices.

Modulating the Schottky barriers of metal-2D perovskite junctions through molecular engineering of spacer ligands.

The crucial role of spacer ligands in affecting the contact properties of metal-2D perovskite junctions, which can severely affect device performance, is revealed in this work. We studied the contact properties of Ag, Au, and Pt with 2D perovskites that possess ligands with different sizes and functional groups. It is found that the interface binding energy, Schottky barrier height (SBH), and tunneling property depend strongly on the ligand size and functional group type. Small-size ligands can induce effective interface coupling and result in perturbed perovskite electronic properties and a high tunneling probability. In addition, high work-function metals and more electronegative functional groups can induce more severe band shifts at the interface. The features of diverse ligands ensure a widely tunable SBH ranging from 0-1.07 eV. This study provides guidance for developing more effective 2D perovskite-based electric nanodevices by tuning the contact properties through molecular engineering of spacer ligands.