Influence Of Substituents Research Articles

Identification of new structure of indol-3-acetyl-arylsulfonohydrazide as potent α-glucosidase and α-amylase inhibitors and molecular docking

Herein this work, indole analogs (1-16) were synthesized by treating 2-(1H-indol-3-yl)acetohydrazide with various aryl sulfonyl chloride in pyridine as solvent and screened for α-amylase and α-glucosidase inhibitory activity under positive control of standard drug acarbose (IC50 = 12.80 ± 0.10 μM /12.90 ± 0.10 μM. All analogs of the series appeared with excellent to good inhibitory activity as compared to standard drug. The inhibitory activity range for α-amylase is 0.70 ± 0.01 μM to 19.40 ± 0.40 μM, while for α-glucosidase inhibitory activity is 1.20 ± 0.10 μM to 20.40 ± 0.40 μM respectively. Most of the analogs appeared with excellent inhibitory activity, and some analogs like 5, 6, 7, 8, 9, 10,13 and 14 for both enzymes displayed many folds better inhibitory activity than standard drug acarbose. The influences of substituents on inhibitory activity were superficially resonated via structure activity relationship. Docking studies were established to confirm the binding interaction between analogs and active sites of enzymes.

Synthesis, Molecular Docking, and Biological Evaluation of Novel Indole-triazole Conjugates.

Indole-triazole conjugates have emerged as promising candidates for new drug development. Their distinctive structural characteristics, coupled with a wide array of biological activities, render them a captivating and promising field of research for the creation of novel pharmaceutical agents. This study aimed to synthesize indole-triazole conjugates to investigate the influence of various substituents on the functional characteristics of indole-triazole hybrids. It also aimed to study the binding modes of new hybrids with the DNA Gyrase using molecular docking studies. A new set of indole-triazole hybrids was synthesized and characterized using various physicochemical and spectral analyses. All hybrids underwent in-silico pharmacokinetic prediction studies. The antimicrobial efficacy of the hybrids was assessed using tube dilution and agar diffusion methods. Additionally, the in-vitro antioxidant activity of synthesized compounds was determined using the 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging assay. Furthermore, in silico molecular docking studies were performed to enhance our comprehension of how the synthesized compounds interact at the molecular level with DNA gyrase. Pharmacokinetic predictions of synthesized hybrids indicated favourable pharmacokinetic profiles, and none of the compounds violated the Lipinski rule of five. Notably, compound 6, featuring a cyclohexanol substituent, demonstrated superior antimicrobial and antioxidant activity (EC50 value = 14.23 μmol). Molecular docking studies further supported the in vitro antioxidant and antimicrobial findings, revealing that all compounds adeptly fit into the binding pocket of DNA Gyrase and engaged in interactions with crucial amino acid residues. In summary, our research underscores the efficacy of molecular hybridization in shaping the physicochemical, pharmacokinetic, and biological characteristics of novel indole-triazole derivatives.

Benchmarking luminescent properties of the arylvinylpyrimidine scaffold.

The exploration of the photophysical properties of push-pull molecules incorporating pyrimidine rings as electron-attracting moieties in their structure continues to be a fascinating area of investigation. A thorough examination of these properties not only contributes to fundamental knowledge but also provides crucial insights for the rational design of emissive materials in prospective applications. In this context, this work conducts an in-depth analysis of four families of 4,6-bis(arylvinyl)pyrimidines, evaluating the influence of substituents on both the aryl groups and position 2 of the pyrimidine ring. While previous research has primarily focused on solution studies, this work emphasizes the importance of examining solid-state photophysics. Through a multidisciplinary approach encompassing optical techniques, x-ray diffraction, and quantum chemical calculations, a comprehensive understanding of the structure-property relationships is achieved. This study underscores the intricate interplay between molecular structure, aggregation, and fluorescence behavior in pyrimidines, offering valuable insights with broader implications beyond academic realms.

Isocyanide Substituent Influences Reductive Elimination versus Migratory Insertion in Reaction with an [Fe2(μ-H)2]2+ Complex.

Iron hydrides are proposed reactive intermediates for N2 and CO conversion in industrial and biological processes. Here, we report a reactivity study of a low-coordinate di(μ-hydrido)diiron(II) complex, Fe2(μ-H)2L, where L2- is a bis(β-diketiminate) cyclophane, with isocyanides, which have electronic structures related to N2 and CO. The reaction outcome is influenced by the isocyanide substituent, with 2,6-xylyl isocyanide leading to H2 loss, to form a bis(μ-1,1-isocyanide)diiron(I) complex, whereas all of the other tested isocyanides insert into the Fe-H bond to give (μ-1,2-iminoformyl) complexes. Steric bulk of the isocyanide substituent determines the extent of insertion (i.e., into one or both Fe-H-Fe units) with tert-butyl isocyanide reacting to yield the mono-(μ-1,2-iminoformyl)diiron(II) complex, exclusively, and isopropyl- and methyl isocyanides affording the bis(μ-1,2-iminoformyl)diiron(II) products. Treatment of Fe2(μ-1,2-CHNtBu)(μ-H)L with 2,6-xylyl isocyanide (or XylNC) yields Fe2(μ-XylNC)2L and tert-butylaldimine as one of the organic products.

Anionic N-Heterocyclic Carbenes from Mesoionic Imidazolium-4-pyrrolides: The Influence of Substituents, Solvents, and Charge on their 77Se NMR Chemical Shifts.

Mesoionic compounds are the starting material for the synthesis of unique anionic N-heterocyclic carbenes. Herein, mesoionic imidazolium pyrrolides synthesized from pyrrole-2-carbaldehyde via various N-alkyl-4-pyrroyl-imidazoles are described. These were converted into nine new 4-(pyrrol-2-yl)-substituted imidazolium salts and transformed into the mesoionic title compounds using an anion exchange resin. The DFT-calculated (B3LYP/6-311++G**) CREF values indicate a great potential for the formation of anionic N-heterocyclic carbenes by deprotonation, which were generated and reacted with selenium to obtain selenoureas. The 77Se NMR shifts investigated under systematic variation of conditions are dependent on the substitution pattern (ΔδSe = 133 ppm) and the steric demand of the substituents. Solvent dependencies of the 77Se NMR shifts were investigated applying toluene-d8, THF-d8, CDCl3, CD2Cl2, pyridine-d5, acetone-d6, DMSO-d6, CD3CN, AcOD, and MeOD. The influences of the referencing method on the 77Se shifts using external or internal Me2Se or Ph2Se2 and solvent can add up to ΔδSe = ca. 80 ppm. In addition, we observed a temperature dependence of both the selenoureas and the reference reagent Ph2Se2 as well as a 77Se shift difference of the analyte caused by interaction with internally added Ph2Se2. The negative charge of deprotonated selenoureas shifts the values by an additional -20 ppm.

Influence of Peripheral Substituents on Fe(II) Spin State in Complexes with Tridentate Schiff‐Base Ligands

AbstractSix Fe(II) complexes with substituted 6‐((quinoline‐8‐ylimino)methyl)phenolates (R2qsal) were synthesized. X‐ray crystal structure determination for [Fe(R2qsal)2], where R=F (1), Cl (2), Br (3), I (4), CF3/H (5), or CN/H (6), revealed mononuclear complexes that crystallize either solvent‐free in case of 1, 5, and 6 or as CH2Cl2 solvates in the case of 2, 3, and 4. Complexes 1–4, which contain π‐donating substituents, exhibit only high‐spin (HS) state, as shown by crystal structure analysis and magnetic measurements. In contrast, complexes 5 and 6, which contain electron‐withdrawing substituents, exist in the low‐spin (LS) state at lower temperatures but exhibit crossover to the HS state above 300 K. Electronic structure calculations show a good correlation between the relative energies of the LS and HS states and the experimentally observed behavior.

Aromatic Difluoroboron β-Ketoiminate Complexes: Effect of Substituents on Mechanofluorochromism and Polymorphic Behavior.

Aromatic difluoroboron β-ketoiminate complexes (ketimBF2) are structural nitrogen-containing analogues of aromatic difluoroboron β-diketonates (diketBF2). Aggregation-induced emission (AIE) and polymorphic behavior allow ketimBF2 to exhibit mechanofluorochromic (MFC) properties. A detailed comparative study of the luminescence of a wide range of ketimBF2 with H- and CH3-substituents of nitrogen atom and diketBF2 with various substituents of the chelate ring (methyl, phenyl, toluoyl, anisoyl, biphenyl, naphthyl, anthracyl) in the solid state was carried out. As a result, regularities of the influence of substituents on the luminescent and MFC properties for 21 dyes have been established. Replacing one oxygen atom in diketBF2 with nitrogen atom in the chelate ring (H-substituted ketimBF2) changes the nature of the molecular stacking in crystals, which is manifested in different MFC properties. The introduction of a methyl group into the chelate ring (CH3-substituted ketimBF2) induces steric hindrance, which prevents the efficient formation of supramolecular structures and, consequently, leads to the shortest-wavelength monomeric emission in the solid state in comparison with oxygen and H-substituted nitrogen analogues. Methoxy derivative of H-substituted ketimBF2 exhibits non-reversible fluorochromic switching after annealing and can be used as temperature indicator to control unauthorized heating of temperature-sensitive substances during transportation and storage.

Synthesis, biological evaluation, molecular docking and dynamic simulation of novel benzofuran derivatives as potential agents against Alzheimer's disease

We have synthesized novel benzofuran derivatives (1–20), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives showed inhibitory activities having IC50 values ranging from 0.70 ± 0.01 to 28.10 ± 0.50 µM (against AChE), while 0.80 ± 0.01 to 31.20 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.50 ± 0.10 µM, respectively). Except derivative 5, all other derivatives of the series showed good inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, but some analogues like 2, 4, 7, 14, 15, and 16 displayed many folds better inhibitory activity than the standard drug donepezil. The influences of substituents on inhibitory activity were superficially resonated via the structure-activity relationship. We established molecular docking and MD simulation studies to confirm the binding interaction between potent derivatives and active sites of enzymes.

Influence of substituents in bis(2-amino-5-R-phenyl)disulfide on the deposition processes and properties of nickel-phosphorus coatings

Influence of substituents in bis(2-amino-5-R-phenyl)disulfide on the deposition processes and properties of nickel-phosphorus coatings

Influence of Substituents on the Vectorial Difference Static Dipole Upon Excitation in Synthetic Bacteriochlorins.

Organic dye aggregates have been shown to exhibit exciton delocalization in natural and synthetic systems. Such dye aggregates show promise in the emerging area of quantum information science (QIS). We believe that the difference in static dipole (Δd) is an essential dye parameter in the development of molecular QIS systems. However, a foundational understanding of the structural factors influencing Δd remains elusive. Bacteriochlorins play a vital role in photosynthesis due to their exceptional photophysical properties. Therefore, bacteriochlorins are particularly suitable dyes for the construction of aggregate systems for QIS. Synthetic bacteriochlorins further offer stability and tunability via chemical modifications. Here, the influence of substituents on the Δd of monomeric (nonaggregated) dyes was investigated via density functional theory (DFT) and time-dependent (TD)DFT in a set of 5-methoxybacteriochlorins progressively substituted with ethynyl, phenyl, and phenylethynyl substituents at the 3,13 and 3,13,15 positions of the macrocycle. Symmetrically substituted 5-methoxybacteriochlorins were shown to have the largest Δd. The increase in Δd in the series of dyes was largely due to changes in the orientation of the static dipole upon excitation rather than large changes in magnitude. In addition, the transition dipole (μ) and the angle between Δd and μ (ζ) were calculated. Three 5-methoxybacteriochlorins with large predicted Δd and μ values were synthesized and characterized spectroscopically. The trend in Δd values empirically determined using the solvatochromic Stokes shift method was comparable to the DFT calculations.

Structural and spectroscopic characterization of N1,N2-diphenylacenapthylene-1,2-diimines and the influence of substituents on the viscosity of alkyl magnesium solutions

Butyl octyl magnesium solutions are important raw materials in various chemical processes but suffer from their high reactivity with even traces of water, protic solvents or oxygen and an increased viscosity in hydrocarbon solution due to the formation of polymeric structures. N1,N2-diphenylacenaphthylene-1,2-diimines (BIANs) have already been identified as potential candidates to reduce the viscosity of alkyl magnesium solutions and this study provides a systematic insight into the dependence of this ability on the position and structures of substituents on the BIAN. Besides the various BIANs, ZnCl2 complexes and hydrogenated derivatives were characterized and tested for their ability to reduce the viscosity. HPLC-high resolution mass spectrometry, MALDI-ToF mass spectrometry, but most important FTIR and NMR experiments under inert conditions have been used to shine light on the interaction of the different BIAN derivatives with alkyl magnesium solutions. Hydrogenated BIANs, especially those with bulky alkyl groups in the ortho position(s) have been identified as the most promising candidates. An additional benefit of the hydrogenated species is that in contrast to BIANs and BIAN-Zn complexes they do not undergo permanent chemical modification and can be reused after extraction.

Alkylphenyl-substituted imidazolines as corrosion inhibitors: experimental and DFT study

A series of steel corrosion inhibitors based on poly(alkyl-phenyl)-2-imidazolines was synthesized from available reagents. Electronic parameters that influence binding to a metal surface have been determined, and the influence of substituents on the geometry of binding to the surface has been studied. The resulting compounds have a degree of protection of steel in hydrochloric acid solutions in individual form above 98% at 60 °C and in a mixture with urotropine more than 99% at 95 °C.

3-Thioxo-3H-indolizinium-1-olates and Related Pseudo-Cross-Conjugated Heterocyclic Mesomeric Betaines: Synthesis and Spectral Features.

The first example of the synthesis of 3-thioxo-3H-indolizinium-1-olates, which further expands a limited class of pseudocross-conjugated heterocyclic mesomeric betaines isoconjugate to odd nonalternant hydrocarbon anion, is reported. These unique, moderately colored heterocyclic products result from a developed three-component reaction of cyclopropenones, pyridines, and sulfur. The protocol is distinguished by simple and mild reaction conditions that avoid expensive reagents or exotic catalysts, exhibiting high functional group tolerance. The broad scope of the reaction is particularly remarkable in light of the dramatic influence of pyridines' substituents on the reactivity of corresponding indolizin-1-ols, the key intermediates that proved to be highly thiophilic. In addition, an oxidative coupling of indolizin-1-ol in situ with p-tropoquinone oxime acetate is discovered. The reaction involves the C3 and C5 positions of the indolizin-1-ol and results in unusual indolizine-aminotropolone combinations. For the 3H-indolizinium-1-olate type of PCC HMBs, some general considerations concerning light absorption and NMR regularities were formulated.

The influence of the pyridyl substituent in N-methyl-P,P-diphenyl-N-2-pyridinyl-phosphinous amide ligand on the coordination chemistry of group 6B metal carbonyl derivatives

The reaction of N-methyl-P,P-diphenyl-N-2-pyridinyl-phosphinous amide (1) with group 6B metal hexa, tetra, and tricarbonyls yielded the same octahedral complexes cis-M(CO)4[1-κ2P,Npy] (M = Cr(2), Mo(3), W(4)) in which the ligand chelates only in a bidentate fashion through its phosphorus atom and pyridyl N-atom. Compounds 1–4 were identified and characterized by multinuclear NMR spectroscopy (1H, 13C, 31P NMR), elemental analysis, IR and UV–Vis spectroscopy. Complexes 2–4 exhibited weak metal-to-ligand charge transfer transitions unaffected by solvent polarity. Crystal structure determination is carried out on complex 4.

A Structure-Activity Relationship Study on the Antioxidant Properties of Dithiocarbamic Flavanones.

The antioxidant properties of 3-dithiocarbamic flavanones have been investigated. The influence of the halogen substituents on ring A of the flavanones and the nature of the secondary amine from the dithiocarbamic moiety have been accounted. The results indicated that the presence of a halogen substituent at the C-8 position of the benzopyran ring induce better antioxidant properties against DPPH and ABTS than butylated hydroxytoluene (BHT) and ascorbic acid. The presence of a halogen substituent at the mentioned position appears to induce a higher stability for a free radical intermediate at the C-3 position of the benzopyran ring. A free radical enolate is most likely to be involved in the antioxidant activity of this dithiocarbamic flavanone. It is a stable intermediate that supports the influence of dithiocarbamic moiety on the antioxidant properties of the reported flavanones.

Synthesis, molecular modelling and evaluation of larvicidal efficacy of annulated Benzo[h]chromenes against Culex pipiens L. Larvae

A new series of substituted benzo[h]chromene, benzochromenopyrimidine, and benzochromenotriazolopyrimidine derivatives were synthesized via chemical transformations of iminonitrile, ethoxymethylene amino, and cyanomethylene functionalities. The chemical structures of the synthesized compounds were assured by spectroscopic data and elemental analysis. The larvicidal efficacy of these compounds against Culex pipiens L. larvae was investigated, revealing potent insecticidal activity, particularly for compounds 6, 10, and 16, exceeding that of the standard insecticide chlorpyrifos. The mode of action of these compounds was explored through molecular docking studies, indicating their potential as acetylcholine esterase (AChE) inhibitors and nicotinic acetylcholine receptors (nAChR) blockers. The structure–activity relationship analysis highlighted the influence of substituents and fused heterocyclic rings on larvicidal potency. These findings suggest that the synthesized compounds hold promise as potential candidates for developing novel and effective mosquito control agents.

Comprehensive Review of Synthesis, Optical Properties and Applications of Heteroarylphosphonates and Their Derivatives.

This review focuses on optical properties of compounds in which at least one phosphonate group is directly attached to a heteroaromatic ring. Additionally, the synthesis and other applications of these compounds are addressed in this work. The influence of the phosphonate substituent on the properties of the described compounds is discussed and compared with other non-phosphorus substituents, with particular attention given to photophysical properties, such as UV-Vis absorption and emission, fluorescence quantum yield and fluorescence lifetime. Considering the presence of heteroatom, the collected material was divided into two parts, and a review of the literature of the last thirty years on heteroaryl phosphonates containing sulfur and nitrogen atoms in the aromatic ring was conducted.

Total synthesis of Comfreyn A and structural analogues via two photochemical key steps.

In this work the influence of o-fluorine substituents on the photo-dehydro-Diels-Alder (PDDA) reaction was investigated and the findings of this study were applied to the total synthesis of natural products. The reactant molecules consisted of two alkyl arylpropiolates, connected by a suberic acid tether and bearing fluorine substituents in each of the o-positions. While quantum chemical calculations suggested that a fluorine substituent prevents an attack of the adjacent carbon atom in the second C-C bond forming step of the PDDA reaction, this attack took place nevertheless. The subsequent fluoride elimination, assisted by protic solvents or trialkylsilanes, resulted in an "Umpolung" of the 4-position of the cycloallene intermediate enabling the introduction of nucleophiles at this position. The nucleophilic replacement of the second fluorine substituent could also be triggered photochemically. After removal of the tether, the two arene moieties stand nearly perpendicular to each other and a selective excitation of the naphthalene moiety was possible. This led to an intramolecular photoinduced electron transfer (PET) followed by a nucleophilic replacement of the fluoride according to a SR+N1Ar* mechanism. The formed phenolic hydroxyl group underwent spontaneous lactonization with the adjacent ester group. Based on these results, the first total synthesis of the lignan Comfreyn A and some structural analogues were developed.

Synthesis and Characterization of Symmetrical N-Heterocyclic Carbene Copper(II) Complexes-An Investigation of the Influence of Pyridinyl Substituents.

Three new tridentate copper(II) N-heterocyclic carbene (NHC) complexes have been obtained and characterized with symmetrical C-4 substitutions on their pendent pyridine rings. Substitutions including methyl (Me), methoxy (OMe), and chloro (Cl) groups, which extend the library pincer Cu-NHC complexes under investigation, modify the impact of pyridinyl basicity on NCN pincer complexes. Both ligand precursors and copper(II) complexes are characterized using a range of techniques, including nuclear magnetic resonance (NMR) spectroscopy for 1H, 13C, 31P, and 19F nuclei, electrospray ionization mass spectrometry (ESI-MS), X-ray crystallography, cyclic voltammetry, and UV-Vis spectroscopy. The pyridine substitutions lead to minimal changes to bond lengths and angles in the X-ray crystal structures of these related complexes; there is a pronounced impact on the electrochemical behavior of both the ligand precursors and copper complexes in the solution. The substitution in the pyridinyl units of these complexes show an impact on the catalytic reactivity of these complexes as applied to a model C-N bond-forming reaction (CEL cross-coupling) under well-established conditions; however, this observation does not correlate to the expected change in basicity in these ligands.

Multisite Amino‐Allylidene Ligands from Thermal CO Elimination in Diiron Complexes and Catalytic Activity in Hydroboration Reactions

AbstractThe new diiron(I) complexes [Fe2Cp2(μ‐CO){μ‐k3C,kN‐C(R1)C(R2)C(CN)NMe(R)}], 3 a–o (R=alkyl or 4‐C6H4OMe; R1=alkyl, aryl, ferrocenyl (Fc), thiophenyl, CO2Me or SiMe3; R2=H, Me or CO2Me) were synthesized in moderate to high yields from the thermal decarbonylation of the bis‐carbonyl precursors 2 a–o, and were structurally characterized by IR and NMR spectroscopy, and single crystal X‐ray diffraction in four cases. Electrochemical behavior of one complex was also investigated. Complexes 3 a–o comprise a highly functionalized, multisite amino‐(cyano)allylidene ligand, including metal coordination of a tertiary amine group. Selected complexes displayed negligible to moderate catalytic activity in CO2/propylene oxide coupling, working under ambient conditions. Additionally, they were investigated as catalysts for the conversion of benzaldehyde to the corresponding borate ester 6 a, using pinacolborane (HBpin) as the borylating agent. Most complexes achieved good conversions at room temperature with 1 % catalyst loading, and data highlight the significant influence of the multisite ligand substituents on the catalytic performance. Notably, complex 3 m (featuring R=4‐methoxyphenyl, R1=Fc, R2=H) displayed the highest activity and effectively catalyzed the hydroboration of various aldehydes and ketones. A plausible mechanistic cycle involves metal coordination of the carbonyl substrate, its activation being possibly facilitated by intramolecular interactions.