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Synthetic design of new functional molecules remains the main route to obtaining the next generation of sensor materials, and the undesirable consequences of environmental heavy metal burdens call ...

Background Our previous reports demonstrated the prospects of a new series of imidazoles as a source of alternative anti-parasite treatments, thus warranting further studies that include toxicity profiling. Objective In this study, we evaluated three imidazoles: bis-imidazole (compound 1), phenyl-substituted 1H-imidazole (compound 2), and thiopene-imidazole (compound 3) for cellular toxicity and possible mechanisms. Methods The three (3) compounds were assessed for in vitro cytotoxic action. Additionally, we probed likely mechanistic actions of these imidazoles. Findings showed dose-dependent cellular toxicity by these imidazoles. Results In the presence of antioxidant (Trolox), cytotoxicity was improved for compounds 2 and 3 but not for compound 1. Meantime, compound 7 promoted reactive oxygen species (ROS) production, which was abated in the presence of a standard antioxidant (Trolox). Additionally, the three (3) imidazoles impaired mitochondrial membrane potential (MMP). While MMP was not restored after treatment removal, the addition of antioxidant (Trolox) improved MMP for compounds 2 and 3 treatment. Additionally, compound 1 elevated expression of hypoxia-inducing factor 1-alpha (HIF-1α). This may not be unconnected with the capacity of compound 1 to cause oxidative stress. Conclusion We show evidence that supports the cytotoxic action of imidazoles involves likely impairment to redox balance and mitochondrial membrane potential. The findings help our understanding of the mechanistic action of these imidazoles in living cells, and altogether may boost their prospects as new and alternative anti-protozoans.

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1–8), phenyl-substituted 1H-imidazoles (compounds 9–19), and thiopene-imidazoles (compounds 20–26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure–activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.

In transition-metal-mediated catalysis, designing new, well defined coordination architectures and subjecting them to catalysis testing under the same reaction conditions is a necessary tool for gaining an improved understanding of desirable active site geometries and characteristics. In this work, three ligands varying in chelation and charge characters (1 = tridentate, dianionic N^N^N; 2 = bidentate, dianionic N^N; 3 = bidentate, neutral N^O) were synthesized and introduced as organic backbones around cobalt(II) centres. Four multinuclear coordination assemblies incorporating various group I metal ions (i.e., (Na-Co1-i)2, (Na-Co1-e)2, (K-Co1-e)2 and (Cs-Co1-e)2) and two mononuclear complexes (i.e., Co2 and Co3) were isolated, structurally characterized and studied as phenoxazinone synthase models. X-ray data and Continuous Shape Measure (CShM) calculations described unusual vacant trigonal bipyramidal geometries for (Na-Co1-i)2, (Na-Co1-e)2 and Co3, trigonal bipyramids for (K-Co1-e)2 and (Cs-Co1-e)2, and a tetrahedron for Co2. According to mass spectrometry data, the four multinuclear (MI-Co1-solvate)2 complexes of ligand 1 easily dissociate in solution to yield the corresponding ions including a common mononuclear Co1 unit. Testing as models in the oxidative coupling of o-aminophenol revealed that an increasing chelate character of the organic ligand backbone produces an undesirable catalyst activity reduction. Furthermore, the similarity in coupling efficiencies observed among complexes (Na-Co1-i)2, (Na-Co1-e)2, (K-Co1-e)2 and (Cs-Co1-e)2 proves that the presence of varying group I metal ions contributed no catalytic effects to the coupling efficiencies and that the Co1 species, which is generated by dissociation in solution, is the only active species responsible for the observed biomimetic behaviours. Therefore, the combination of anionic chelate ligands with easily detachable, neutral co-ligands (e.g., water or pyridine) around a cobalt(II) centre could be recommended for the generation of a successful catalyst material, rather than the combination of a neutral chelate ligand with counter-anionic monodentate co-ligands like halides.

A series of synthetically accessible ligands based on new 2-(R-sulfonamido)benzamide have been prepared (R = methyl for H3M; R = 4-toly for H3T and T2CN; R = 2,4,6-triisopropylphenyl for H3iP and HiPCN). The R-substituents were selected to vary in sizes. Allowing ligand H3iP and palladium acetate to stand in solvent leads to self-assembly of the well-defined solvent- and stoichiometry-controlled tetranuclear or hexanuclear coordination macromolecules Pd4(iP)2 and (PdHiP)6, which were analysed by X-ray crystallography. It was observed that palladium active species for Suzuki coupling catalysis could be stabilized by these simple and synthetically assessable N-donor ligands as revealed by turnover frequencies reaching 5500 h−1. Electronic features of these N-donors appear to be more important than the steric properties.

The Trypanosoma spp. cause animal and human trypanosomiasis characterized with appreciable health and economic burden mostly in developing nations. There is currently no effective therapy for this parasitic disease, due to poor drug efficacy, drug resistance, and unwanted toxicity, etc. Therefore, new anti-Trypanosoma agents are urgently needed. This study explored new series of imidazoles for anti-Trypanosoma properties in vitro and in vivo. The imidazoles showed moderate to strong and specific action against growth of T. congolense. For example, the efficacy of the imidazole compounds to restrict Trypanosoma growth in vitro was ≥ 12-fold specific towards T. congolense relative to the mammalian cells. Additionally, the in vivo study revealed that the imidazoles exhibited promising anti-Trypanosoma efficacy corroborating the in vitro anti-parasite capacity. In particular, three imidazole compounds (C1, C6, and C8) not only cleared the systemic parasite burden but cured infected rats after no death was recorded. On the other hand, the remaining five imidazole compounds (C2, C3, C4, C5, and C7) drastically reduced the systemic parasite load while extending survival time of the infected rats by 14 days as compared with control. Untreated control died 3 days post-infection, while the rats treated with diminazene aceturate were cured comparable to the results obtained for C1, C6, and C8. In conclusion, this is the first study demonstrating the potential of these new series of imidazoles to clear the systemic parasite burden in infected rats. Furthermore, a high selectivity index of imidazoles towards T. congolense in vitro and the oral LD50 in rats support anti-parasite specific action. Together, findings support the anti-parasitic prospects of the new series of imidazole derivatives.

Widespread use of commercially available palladium precatalysts is limited by high costs and their synthetic challenges. In this report, series of synthetically affordable, phosphine-free ligands were examined as supports for palladium active centers. 2-(2-Aminoethylamino)ethanol, diethylenetriamine and tris(2-aminoethyl)amine were condensed with sulfonyl chloride reagents in order to obtain flexible, aliphatic amine derivatives with varied steric bulk at the chain ends (ligands 1-Me and 1-tol = RSO2 NH CH2CH2 N(SO2R) CH2CH2Cl; ligands 2-ipr and 2-iprNH = RSO2 NH CH2CH2 NY CH2CH2 O SO2R where Y is H or R; ligands 3-Me, 3-tol and 3-ipr = RSO2 N(CH2CH2 NH SO2R)2; 3-iprNH = HN(CH2CH2 NH SO2R)2; ligands 4-tol and 4-ipr = N(CH2CH2 NH SO2R)3; R = methyl, tolyl or triiso-propyl). Despite the flexibility of the alkyl fragments in these ligands, placement of sterically demanding groups at amine donors enables formation of active species, which supports high turnover frequencies and yields up to 91% within 5 min and at 0.2 mol % palladium loading. Such activity from synthetically simple alkyl ligand frameworks, which are generally not regarded in Pd catalysis, is unprecedented. In situ catalyst generation is favorable for ligands with less than tridentate chelation capacity and presence of poorly chelating secondary NH-amine donor in the central position of the polyamines hinders catalyst performance. However, the preformed tridentate complexes yielded more attractive and living coupling catalyst efficiencies than their corresponding in situ reactions especially when bulkier co-ligand such as pyridine occupies the fourth coordination position (TOF of 5460 h−1 for Pd(4-tol)py and 4800 h−1 for Pd(4-ipr)py). Therefore, mutual steric demands between the tridentate-chelated steric ligands such as 4-tol and 4-ipr, and bulky co-ligand fragments cooperatively aids the generation of active species from assembled precatalyst.

The importance of phenoxazinone chromophore has inspired chemists to develop new synthetic models that can mimic phenoxazinone synthase activity. However, a systematic approach for the investigation of structure–property correlation of model complexes based on the appreciable number of structurally varied and well-defined complexes is scarce. In this study, two new diazene–disulfonamide ligands RSO2–NH–Ph–NN–Ph–NH–SO2R (where R = methyl (1) and R = tolyl (2)) were deployed along with monodentate N-donors derived from imidazole or pyridyl moieties to assemble mixed-ligand cobalt(II) complexes Co1(im)2, Co1(py)2, Co1(dpy)2, Co2(im)2 and Co2(py)2. Based on the structural characterization results, the diazene–disulfonamide ligands coordinated as tridentate dianionic N^N^N-donors, while two units of the monodentate N-donors aided to complete a square-pyramidal geometry around each cobalt(II) metal centres. Continuous shape measurements (CShM) calculations were carried out to further clarify the distorted square-pyramidal geometry as a vacant octahedral vOC-5 (C4v) coordination environment. A comparative study of the phenoxazinone synthase mimicking behaviour of the complexes was conducted and the results led to conclusions that the transition cobalt(II) active sites performed better when uncrowded and in the presence of readily detachable co-ligands. Consequently, from the experimental point of view, the remarkable reactivity of metallo-enzymes was pictured to depend on the availability of vacant metal coordination positions that are not sterically clogged.

The need to explore possible benefits of molecular substituent derivatization on fluorescent chemosensor properties motivated the syntheses of six potentially pentadentate bis-(phenol-imine) fluorophores, which consist of five S-bridged O^N^S^N^O scaffolds 1–5 and an O-bridged O^N^O^N^O scaffold 6. The deliberate incorporation of multiple intramolecular N…H O donor–acceptor functions into the molecules helped to achieve Excited State Intramolecular Proton-electron Transfer (ESIPT) capability as well as the possession of low quantum yields in their ligand-only solutions. Interestingly, while the low quantum yield molecules 1, 2, 3 and 6 lacked the expected large Stokes shifted ESIPT fluorescence in their ligand-only solutions, they utilize the same ESIPT-oriented process to achieve varying extents of substituent-dependent fluorescent turn-on that produced sensitive and selective Al3+ detection. In particular, while molecules 1 and 3 gave dual-band fluorescence turn-on from both primary and secondary photoexcited states, the O-bridged ligand 6 is strongly turned on only at the large Stokes shifted ESIPT emission wavelength. Thus, with a 528-fold F/Fo turn-on ratio and a detection limit of 5.48 × 10−9 M, the efficiency of molecule 6 as chemosensor towards Al3+ detection can be considered to be outstanding. Based on results of Job plot experiment, fluorescent intensities during Al3+ titration, single crystal structural data and 1H NMR spectral analyses, we conclude that a 1:1 sensor-to-analyte stoichiometry is at play in the Al3+ sensing mechanism and that the sensor molecules form an unusual bidentate O^O coordination with the analyte as neutral iminium zwitterion. It could be concluded that synthetic designs leading to systematic substituent variation is a beneficial tool for tuning and isolating applicable molecular chemosensor species.

Mixed ligand copper(II) complexes of Benzoyltrifluoroacetone (BTAH) with 1,10-phenanthroline (Phen) and 2,2′-bipyridine (Bipy) were synthesized and characterized. These complexes, namely [Cu(BTA)(Phen)(NO3)] (1), [Cu(BTA)(Phen)Cl] (2), [Cu(BTA)(Bipy)(NO3)] (3), [Cu(BTA)(Bipy)Cl] (4), and [Cu(BTA)(Phen)Br]•H2O (5), were characterized by elemental analysis; spectral; magnetic and molar conductance measurements; mass spectrometry; thermal analysis and antimicrobial susceptibility testing. The structures of 1 and 4 contained square pyramidal copper(II) environments. The microbiostatic activity revealed that the copper complexes showed pronounced activity in all the tested bacteria, except in Klebsiella pneumonia, Escherichia coli and Salmonella enterica in which some of the complexes were moderately active on the bacterial strains.

A series of structurally and electronically varied 2,6-di(1H-imidazol-2-yl)phenols that are ESIPT-capable (1–12) as well as the ESIPT-incapable 4,5-diphenyl-2-(3-(4,5-diphenyl-1H-imidazol-2-yl)phenyl)-1H-imidazole (13) were designed and comparatively studied for their molecular effects on their sensitivity and selectivity characteristics as fluorescent chemosensors of Cr3+, Zn2+, and Cd2+. Their single-crystal structures revealed a desired chain of intramolecular hydrogen bonding (ligand 12) as well as possible coordination modes. Probes 1–4 demonstrated very high turn-on sensitivity and selectivity as double fluorescent sensors for Cr3+ and Zn2+ at their different emission wavelengths (blue-shifted in the case of Zn2+). A remarkable 106-fold emission turn-on by Cr3+ was recorded for molecule 2, which, to the best of our knowledge, is an unheard of magnitude for Cr3+ sensitivity. The results suggested that a Cd2+ sensor could be developed by further derivatization of these probes. The possession of symmetrical substitution on both imidazole rings, multiple active protons involved in hydrogen intramolecular bonding relays, and the consequent ESIPT capability of the studied molecules were found to be very beneficial to their successful outcomes as high fluorescent turn-on chemosensors. Modification of the sensor properties, such as sensitivity and selectivity, was achieved through substituent manipulations at certain peripheral positions. Thus, deliberate molecular derivatization was found to be a tool for manipulating the interference and selectivity profiles. The Job plot, single-crystal results, and sustained large Stoke's shift in the presence of Cr3+ suggest a one-pocket N^O coordination in a 1 : 1 stoichiometry rather than a binuclear N^O^N two-pocket coordination. Quantum mechanical calculations on the model structures suggested that the successful turn-on results may be associated with the coplanarity settings of the imidazole and phenol rings.

Background Therapeutic options for toxoplasmosis are limited. This fact underscores ongoing research efforts to identify and develop better therapy. Previously, we reported the anti-parasitic potential of a new series of derivatives of imidazole. Objective In the current investigation, we attempted the investigation of the possible action mechanism of few promising anti-parasite imidazole derivatives namely C1 (bis-imidazole), C2 (phenyl-substituted 1H-imidazole) and C3 (thiophene-imidazole) Methods We evaluated if oxidative stress, hypoxia as well as metabolic reprogramming of host l -tryptophan pathway form part of the parasite growth inhibition by imidazoles. Anti-parasite assay was performed for imidazoles at concentrations ranging from 0 to 10 μM, while pyrimethamine was used as reference drug to validate assay. Results Imidazole compounds restricted parasite growth dose-dependently. However, in the presence of an antioxidant (Trolox), l -tryptophan and/or CoCl2 (chemical inducer of hypoxia), the growth inhibitory efficacy of imidazoles was appreciably abolished. Further, imidazole treatment led to elevated level of reactive oxygen species, while reducing parasite mitochondrial membrane potential compared with control. In contrast, imidazole had no effect on host HIF-1α level suggesting its exclusion in the anti-parasite action. Conclusion Taken together, imidazole-based compounds might restrict parasite growth by causing oxidative stress. The findings provide new insight on the likely biochemical mechanisms of imidazoles as prospective anti-parasite therapy. Data gives new perspective that not only underscores the anti-parasite prospects of imidazoles, but implicates the host l -tryptophan pathway as a feasible treatment option for T. gondii infections.

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1-8), phenyl-substituted 1H-imidazoles (compounds 9-19), and thiopene-imidazoles (compounds 20-26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure-activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity ( 1176 to 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.

Three novel bis-imidazole-phenol dyes 1–3 have been designed with deliberate incorporation of a pair of O–H…N donor-acceptor units on each dye in order to enable Excited State Intramolecular Proton / electron Transfer (ESIPT) capability, its desirable red-shifted emissions and consequent reduction of fluorescence characteristics, which in turn became applicable for fluorescence turn-on response in metal ion sensing. Molecule 1 was confirmed by single crystal X-ray analysis. Their quantum yields in acetonitrile solutions are generally suitable (Φ = 0.30 for 1, Φ = 0.06 for 2 and Φ = 0.08 for 3) and they display fluorescence turn-on sensitivity towards chromium(III). The selectivity features of fluorophores 2 and 3 for Cr(III) are remarkable. The blue-shift of emission bands coupled with the emission turn-on after introduction of Cr(III) confirms that the ESIPT capability of the fluorophores contributes to the low emission properties of the molecules and that emission turn-on during fluorescence detection succeeds by elimination of the ESIPT possibility. Therefore, it could be concluded that the ESIPT feature is a vital tool to utilize for fluorescent sensor designs. Job plot analysis indicates a 2 : 1 stoichiometry of metal : sensor. Results of interference studies also favours potential application of the ESIPT dye 3 for detection of chromium(III). Molecular variation effects were discussed.

A series of six new, bidentate ligands based on N-(2-(R-sulfonamido)benzyl)R-sulfonamide have been isolated as dianionic or monoanionic chelators via condensation of 2-(aminomethyl)aniline with sulfonyl chloride reagents; R=methyl (1 and 1′), tolyl (2 and 2′), 2,4,6-trimethylphenyl (3), or 2,4,6-triisopropylphenyl (4). Complexes of ligands 2–4 reacted at room temperature with palladium(ii) acetate in the presence of various monodentate N-donor co-ligands to form complexes Pd2(2dmap), Pd2′(OAc.py), Pd3(2acn), Pd3(2py), Pd4(2acn), and Pd4(2py), which were structurally confirmed by three X-ray crystal analyses. Results of catalysis studies in water showed high turnover frequencies and yields of up to 98% within 10min and at 0.2 mol-% palladium catalyst loading. Relative to ligand-free catalysis in the presence of only Pd(OAc)2, the ligand-supported palladium species clearly possess positive catalytic advantage. Furthermore, Suzuki coupling efficiencies by 1:1 ‘Pd(OAc)2+ligand’ yielded notably better outcomes than for the 1:2 ‘Pd(OAc)2+ligand’ insitu catalyst generation, which reveals that coordinative saturation is undesirable. The size of the complementing monodentate co-ligand was observed to influence the catalytic efficiency such that bulkier co-ligands consistently yielded improved turnover frequency values, which leads to the conclusion that steric repulsion between the synthesised ligands and the bulkier co-ligands aided the generation of vacant coordination sites for the more active complexes. Moderate Heck coupling activity was recorded for the complexes and better activities appear to correlate with moderate bulkiness of ligand 3.

Most documented investigations deploying transition metal complexes as phenoxazinone synthase models only report one or two complexes, which limits understanding of structure-property correlations between varying compositions as well as the coordination environments of the active site changes and the biomimetic activities. In efforts to systematically investigate changes in the vicinity of cobalt(II), five new complexes of two tripod N,N′,N″-(nitrilotris(ethane-2,1-diyl))tris(benzenesulfonamide) ligand derivatives (1 and 2) were self-assembled with incorporation of Na+, K+ or Cs+ as bridging counter cations. All the complexes were structurally analysed and found to possess distorted trigonal bipyramid cobalt(II) centres such that an easily displaceable water molecule always occupy one of the axial positions. While ligand 1 forms (Na[Co1.w]E)n as a 1D coordination polymer, ligand 2 forms the dimeric complexes (Na[Co2.w]M)2, (Na[Co2.w])2, (K[Co2.w]A)2 and (Cs[Co2.w]M2,w2)2. Continuous Shape Measurement (CShM) calculations were carried out to analyse distortions of the obtained trigonal bipyramid geometries. The high turnover numbers of 584 h−1 for (Na[Co2.w])2, 564 h−1 for (Cs[Co2.w]M2.w2)2, 543 h−1 for (K[Co2.w]A)2 and 446 h−1 for (Na[Co2.w]M)2 represent attractive level of phenoxazinone mimicking capacity relative to literature data for mononuclear cobalt(II) complexes. It was concluded that the release of free cobalt(II) anions [Co1.w]− or [Co2.w]− via dissociations of the multinuclear complexes is necessary for the phenoxazinone synthase mimicking activities to occur and that the incorporated group I metal ions possess no influence on the observed mimicking activities. The trigonal bipyramid coordination environments of the anionic chelates [Co1.w]− or [Co2.w]− yielded better outcomes than their previously reported vacant octahedral (vOC-5, C4v) complex analogues.

Deployment of reduced operational temperatures is industrially beneficial and use of the highly efficient, phosphine-based precatalysts is limited by their high costs and inaccessible preparation procedures. In order to study of the influence of coordination environments on catalyst reactivities at reduced temperatures, design of palladium(II) complexes bearing single monodentate N-donor ligands was considered necessary. Consequently, dichloridopalladium(II) complexes of 2-(thiophen-2-yl)-1H-imidazole ligands (1–8), 2,4,5-triphenyloxazole (9) and 2-(1H-imidazol-2-yl)pyridine (10) have been prepared, structurally characterized and studied as N-stabilized precatalysts. Ligand donor strengths were spectroscopically estimated by protonation-deprotonation equilibria. The palladium(II) complexes were obtained in three coordination environments; (i) the mono-ligand complexes bearing trans-solvent co-ligands (PdL.acn and PdL.dmf), (ii) the chlorido-bridged dimers µ-(PdL)2 and (iii) the trans-bis-ligand PdL2 complexes. Considering ambient temperature operations, the catalysis outcomes obtained for the monodentate mono-ligand coordination designs represent an improvement in terms of temperature and reaction time relative to previously reported N-stabilized palladium precatalysts. The mono-ligand pre-catalysts efficiently generate living active palladium species from 40 °C while a trans-bis-ligand phosphine-based pre-catalyst analogue PdI2(PPh3)2 displayed no yield under the same temperature conditions. Trans-bis-ligand coordination is observed to utterly hinders catalyst efficiencies at the studied temperatures and preformed mono-ligand complexes of mono-dentate N-donors provided positive ligand effects while in situ catalyst generation failed. Therefore, the use of multiple ligand equivalents should be discouraged.

In this report, a series of synthetically affordable phosphine-free ligands (L1 – L4) of the form RSO2–NH–Ph–N N–Ph–NH–SO2R were prepared and examined as organic ligands for stabilizing palladium active centers; R = methyl, tolyl or triiso-propylphenyl. Palladium complexes, which were obtained in varying coordination environments as well as with varying complementary co-ligands (water, acetonitrile or pyridine), have been subjected to Suzuki and Heck coupling experiments in order to study molecular level ligand effects on preferred catalyst settings. The appreciable coupling activities for Suzuki and Heck coupling with functional group tolerance were recorded for palladium species generated from the chelate ligands. Results show that, despite the tridentate chelation characteristics of these azo-benzene ligands, the introduction of bulky units at the sulfonyl groups enabled generation of active palladium species with high turnover frequencies; e.g. 5040 h−1 (84% yield) within 5 min at 0.2 mol % loading of Pd.L2.py in only water as solvent. A correlation between catalytic efficiencies and the bulkiness of the coordinated co-ligand was obtained. However, while Suzuki coupling activity increased with increase in co-ligand sizes of the preformed complexes (i.e. water

A series of new structurally and electronically diversified palladium complexes derived from seven less sterically crowded 2-(4,5-dimethyl-1H-imidazol-2-yl) phenol/2-(4,5-diethyl-1H-imidazol-2-yl) phenol ligands and fourteen 2-(4,5-diphenyl-1H-imidazol-2-yl) phenols/2-(1H-phenanthro[9,10-d]imidazol-2-yl) phenols bearing varying degrees of higher steric bulk have been prepared and characterized. While single crystals grown from precipitated products of complexation reactions confirmed the bis-ligand Pd(N^O)2 coordination, few crystals obtained from reaction filtrates involving the 2-(4,5-diphenyl-1H-imidazol-2-yl) phenols provided evidence for formation of N^O^C chelation species achieved by cyclometallation. Results from structural analyses and catalytic outcomes generally indicate that desirable variables on the ligand frameworks for obtaining superior catalyst activities either provides hemilabile or sterically strained chelation characters, which would both favour generation of monodentate coordination species at the catalysis temperature. In particular, correlation was observed between tendency for cyclometallation in the palladium complexes and poor Suzuki–Miyaura catalytic prospects. Based on hopeful activity obtained for the complex bearing 4-bromo-2-(4,5-dimethyl-1H-imidazol-2-yl) phenol, it was also concluded that sterically bulky ligand is not a necessity for high coupling efficiency, while presence of potentially cyclometallating substituent moieties in the vicinity of the palladium centre may in fact destroy catalytic prospects.

Series of systematically varied 2-(1H-imidazol-2-yl)phenol ligand frameworks, which were synthesized and properly characterized, have been used to investigate favourable ligand characteristics towards in situ formation of active palladium species in Suzuki–Miyaura coupling. Structures of 2-(4,5-diethyl-1H-imidazol-2-yl)-4-nitrophenol (p-N∼de) and 4-(tert-butyl)-2-(4,5-diphenyl-1H-imidazol-2-yl)phenol (p-tBu∼dp) as well as the palladium complex of 2-(4,5-diethyl-1H-imidazol-2-yl)phenol (Pd.de2) were confirmed. Structural analyses show that para-nitro-substituted phenol moieties bear poor oxo-donor atom while the reverse was observed for para-tBu-substituted analogues. Ligand donor strengths were also determined by pKa analysis. Under the same reaction conditions for palladium catalyzed Suzuki–Miyaura coupling in the presence of ‘ligand + palladium(II) acetate’ catalyst system, results show that electronic properties of the ligands are more important than the variation in steric properties. In particular, ligands with strong bidentate chelate coordination potentials acted as poisons while those with monodentate coordination potential proved to be very beneficial towards in situ generation of superior active species. Furthermore, correlation between donor strength pKa data and the trends in catalytic efficiencies as a consequence of ligand presence was studied. Therefore, it was concluded that ligands with strong chelation tendencies adversely impacted in situ palladium catalyst generation efficiency and that there appears to be moderate steric requirement from ligands for optimal catalyst efficiency.

Phenanthroline derivative, 2-(6-methylpyridin-2-yl)-1H-imidazo[4,5-f][1,10] phenanthroline (MIP) was synthesized and characterized by elemental analysis, FT-IR, 1 H NMR, 13 C NMR, and single crystal X-ray diffraction study. MIP was evaluated as corrosion inhibitor for mild steel in 0.5 M H 2 SO 4 solution using gravimetric and UV–Visible spectrophotometric methods at 303–333 K. Results obtained show that MIP acts as inhibitor for mild steel in H 2 SO 4 solution. The inhibition efficiency was found to increase with increase in MIP concentration but decreased with temperature. Activation parameters and Gibbs free energy for the adsorption process using statistical physics were calculated and discussed. The UV–Visible absorption spectra of the solution containing the inhibitor after the immersion of mild steel specimen indicate the formation of a MIP-Fe complex.

Background: Current drugs available for the treatment of Chagas disease are fraught with several challenges including severe toxicity and limited efficacy. These factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against Chagas disease a priority. Objective: This study screened several imidazole-based compounds for anti-Trypanosoma potential. Method: Using an in vitro experimental infection model, several imidazole-based compounds were screened for anti-proliferative effect on Trypanosoma cruzi epimastigotes. Additionally, all test compounds were evaluated for unspecific cytotoxicity on L929 murine fibroblasts. Benznidazole (BZN) served as reference drug. Results: All test compounds demonstrated interesting trypanocidal potential with IC values in the μM range (1< 1C 9.42). Conclusion: We provide evidence which implicate the imidazole-based compounds as potential prototypes for the development of anti-parasitic agents. Findings have far-reaching relevance to drug discovery efforts for trypanosomiasis.

Three mononuclear cobalt(II) complexes based on the 2-(4,5-diphenyl-1H-imidazol-2-yl)phenol ligand and its nitro and methoxy derivatives have been synthesized and investigated. For two of these complexes, which were derived from the parent ligand and its nitro derivative, the molecular structures have been determined by X-ray crystallography. A distorted tetrahedral coordination environment is observed for the cobalt(II) centers with two bidentate N,O ligands. The magnetic properties have been studied by susceptibility and magnetization measurements revealing the presence of high-spin cobalt(II) ions with a considerable zero-field splitting in the order of D = –35 to –41 cm−1 for the three complexes. With an applied dc field the ac susceptibility data reveal a slow magnetic relaxation which is characteristic for single-molecular magnet (SMM) behavior.

A series of 2-R-6-(aryloxazol-/imidazol-2-yl)pyridine and 2,4-di-tert-butyl-6-(1H-phenanthro[9,10-d]imidazol-/oxazol-2-yl)phenol derivatives were synthesized and characterized using elemental and spectroscopic analyses as well as single-crystal X-ray diffraction analysis. The oxazole derivatives displayed higher photoluminescence efficiencies than their imidazole analogues. The 2-(phenanthro[9,10-d]oxazole/imidazol-2-yl)pyridine derivatives displayed quantum yields approaching unity in non-polar solvents but were quenched in polar solvents. The oxazole analogues produced reversible fluorescence photo-switching between 400 nm and 550 nm regions whilst the imidazole analogues underwent an irreversible photo-induced excimer formation in polar solvents. 1H NMR was used to rationalize the proposed mode of intermolecular interactions between excimers of the 2-(phenanthro[9,10-d]imidazol-2-yl)pyridine derivatives.

A new phenanthroline derivative, 2-mesityl-1H-imidazo[4,5-f][1,10]phenanthroline (MEIP), was synthesized and characterized by elemental analysis, FT-IR, 1HNMR, and 13CNMR spectra. MEIP was evaluated as corrosion inhibitor for carbon steel in 0.5 M H2SO4 solution using gravimetric and UV−visible spectrophotometric methods at 303−333 K. Results obtained show that MEIP is a good inhibitor for mild steel in H2SO4 solution. The inhibition efficiency was found to increase with increase in MEIP concentration but decreased with temperature, which is suggestive of physical adsorption mechanism. Activation parameters and Gibbs free energy for the adsorption process using Statistical Physics were calculated and discussed. The UV−visible absorption spectra of the solution containing the inhibitor after the immersion of mild steel specimen indicate the formation of a MEIP-Fe complex. The calculations of global reactivity indices of MEIP such as the localization of frontier molecular orbitals, EHOMO, ELUMO, energy gap ...

A series of new imidazole based heterocycles (5-(4,5-diphenyl-1H-imidazol-2-yl)furan-2-yl)methyl acetate ( Him-dp ), (5-(1H-phenanthro[9,10-d]imidazol-2-yl)furan-2-yl)methyl acetate ( HIm-pt ), (5-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)furan-2-yl)methyl acetate ( HIm-phen ), 2-(2-nitrophenyl)-4,5-diphenyl-1H-imidazole ( HIm-n ), 1-methyl-2-(2-nitrophenyl)-4,5-diphenyl-1H-imidazole ( MeIm-n ), N-(2-(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)phenyl)benzamide ( EtIm-ba ) and 2,4-di-tert-butyl-6-(8-(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)-1,4-dihydroquinolin-2-yl)phenol ( EtIm-q ) were synthesized and studied for the dependence of their azole donor characteristics on substituent factors by means of experimentally determined ionization constant data (derived as p K a s), spectroscopic analyses and calculated properties of their DFT optimized molecular geometries performed at the B3LYP/6-311 + G * level. Results showed that the lowest donor strength recorded for HIm-pt (p K a = 2.67 ± 0.07) could be traced to the extensive electronic conjugation of the azole π-electrons with 4,5- and 2-substituents. On the other hand, the strongest imidazole donor strength in the series was obtained from EtIm-q (p K a = 4.61 ± 0.04) for which the substituents possessed negligible π-overlap with the azole ring. The experimental results and theoretical calculations lead to conclusions that effective conjugation between the imidazole ring and substituent aromatic groups is accountable for significant withdrawal of charge densities on the imidazole N-donor atom and vice versa. Furthermore, observed donor strengths in the series suggest that electronic inductive effects of the substituents provided lesser impact on donor strength modification of imidazole base and that alkylation of 1-imidazole position did not yield the anticipated push of electron density in favour of the N-donor atom. It is anticipated that the results should promote the understanding of azole-containing bio-macromolecular species and reactions as well as tuning and application of azole functions in molecular science.

Series of 2-R1-6-(1-R2-4,5-diphenyl-1H-imidazol-2-yl)pyridine (R1 = R2 = H, L1; R1 = Me, R2 = H, L2; R1 = H, R2 = Me, L3; R1 = R2 = Me, L4), 2-(6-R1-pyridin-2-yl)-1H-phenanthro[9,10-d]imidazole (R1 = H, L5; R1 = Me, L6) and 2-(pyridin-2-yl)phenanthro[9,10-d]oxazole (L7) were synthesized and used to prepare their corresponding dihalonickel complexes (C1–C9). All organic compounds and nickel complexes were characterized by elemental and spectroscopic analyses. Molecular structures of C1, C4, C5 and C8 were confirmed by the single-crystal X-ray diffraction analysis. The single-crystal X-ray analysis revealed complex C1 as a distorted octahedral geometry, complex C4 as a distorted square pyramidal geometry, complex C5 as a distorted trigonal bipyramidal configuration, and complex C8 as a tetrahedral geometry. Upon activation with methylaluminoxane (MAO), the nickel complexes showed good activity towards norbornene polymerization through main additional and minor ring-opening metathesis. The reaction parameters such as norbornene concentration, reaction temperature and different coordinate environments caused by the ligands affected their catalytic performances.

Fourteen new organic molecules A1–A4, B1–B5, C1–C4 and D and a series of transition metal(II) complexes (Ni1–Ni9 and Pd1–Pd2b) were synthesized and studied in order to characterize the hemilability of 2-(1H-imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine ligands (A1–A4 = 2-R2-6-(4,5-diphenyl-1R1-imidazol-2-yl)pyridines, R1 = H or CH3, R2 = H or CH3; B1–B5 = 1-R2-2-(pyridin-2-yl)-1R1-phenanthro[9,10-d]imidazoles/oxazoles, R1 = H or CH3, R2 = H or CH3; C1–C4 = 2-(6-R2-pyridin-2-yl)-1H-imidazo/oxazo[4,5-f][1,10]phenanthrolines, R2 = H or CH3; D = 2-mesityl-1H-imidazo[4,5-f][1,10]phenanthroline). They were also used to study the substituent effects on the donor strengths as well as the coordination chemistries of the imidazole/oxazole fragments of the hemilabile ligands. All the observed protonation–deprotonation processes found within pH 1–14 media pertain to the imidazole or oxazole rings rather than the pyridyl Lewis bases. The donor characteristics of the imidazole/oxazole ring can be estimated by spectroscopic methods regardless of the presence of other strong N donor fragments. The oxazoles possessed notably lower donor strengths than the imidazoles. The electron-withdrawing influence and capacity to hinder the azole base donor strength of 4,5-azole substituents were found to be in the order phenanthrenyl (B series) > 4,5-diphenyl (A series) > phenanthrolinyl (C series). An X-ray structure of Ni5b gave evidence for solvent induced ligand reconstitution while the structure of Pd2b provided evidence for solvent induced metal–ligand bond disconnection. Interestingly, alkylation of 1H-imidazoles did not necessarily produce the anticipated push of electron density to the donor nitrogen. Furthermore, substituents on the 4,5-carbons of the azole ring were more important for tuning donor strength of the azole base. DFT calculations were employed to investigate the observed trends. It is believed that the information provided on substituent effects and trends in this family of ligands will be useful in the rational design and synthesis of desired azole-containing chelate ligands, tuning of donor properties and application of this family of ligands in inorganic architectural designs, template-directed coordination polymer preparations, mixed-ligand inorganic self-assemblies, etc.

New 2-(1H-imidazol-2-yl)phenols ( L1Et – L8 t BuPt ) bearing a phenolic proton in the vicinity of the imidazole base were prepared and characterized. Experimental studies of the dependence of their protonation/deprotonation equilibrium on substituent identities and intramolecular hydrogen bonding tendencies were carried out using electronic absorption spectroscopy at varying pH values. In order to make comparison, 2-(anthracen-10-yl)-4,5-diphenyl-1H-imidazole ( L9Anthr ) bearing no phenolic proton and 4,5-diphenyl-2-(4,5-diphenyl-1H-imidazol-2-yl)-1H-imidazole ( L10BisIm ) bearing two symmetrical imidazole base fragments were also prepared and experimentally investigated. DFT calculations were carried out to study frontier orbitals of the investigated molecules. While electron-releasing substituents produced increase in protonation–deprotonation p K a s for the hydroxyl group, values for the imidazole base were mainly affected by polarization of the imidazole ring aromaticity across the 2-imidazole carbon and the 4,5-imidazole carbons axis of the imidazole ring. It was concluded that electron-releasing substituents on the phenol ring and/or electron-withdrawing substituents on 4,5-imidazole carbons negatively affects donor strengths/coordination chemistries of 2-(1H-imidazol-2-yl)phenols, and vice versa. Change of substituents on the phenol ring significantly altered the donor strength of the imidazole base. The understanding of p K a variation on account of electronic effects of substituents in this work should aid the understanding of biochemical properties and substituent environments of imidazole-containing biomacromolecules.

A series of hemilabile 2-(imidazol-2-yl)pyridine and 2-(oxazol-2-yl)pyridine palladium ligands are synthesized, characterized, and their catalytic properties in high-temperature Suzuki—Miyaura cross-coupling reactions are investigated.

A series of 2-(imidazole-2-yl)phenol ligands L1-L6 with the general composition 4-R(4)-5-R(3)-6-R(2)-2-(4,5-R(1),R(1)-1H-imidazole-2-yl)phenol (L1: R(1) = C(2)H(5), R(2) = R(3) = R(4) = H; L2: R(1) = C(6)H(5), R(2) = R(3) = R(4) = H; L3: R(1) = C(6)H(5), R(3) = OCH(3), R(2) = R(4) = H; L4: R(1) = C(6)H(5), R(4) = OCH(3), R(2) = R(3) = H; L5: R(1) = C(6)H(5), R(3) = H, R(2) = R(4) = CH(3); L6: R(1) = C(6)H(5), R(3) = H, R(2) = R(4) = t-Bu) and L7 (2,4-di-tert-butyl-6-(1H-phenanthro[9,10-d]imidazol-2-yl)phenol) and their neutral Zn(II) complexes (Z1-Z7) were synthesized and characterized by spectroscopic and elemental analyses. Molecular structures of L1, L5, Z1, and Z2 were confirmed by single-crystal X-ray diffraction. L1 crystallized in the monoclinic Cc space group, while L5, Z1, and Z2 all crystallized in the triclinic P1 space group. One-dimensional arrays based on continuous pi-pi stacking interactions and hydrogen bonding were observed for L1 and Z1, while L5 existed as discrete dimeric stack units. Z2 formed hydrogen-bonded 1D network structures but was completely devoid of pi-pi stacking interactions. Emission processes were found to be more dependent on the substituents on phenol as well as condensed media. In contrast to general conclusions on closely related systems in the literature, significant photorelaxation from the excited enol state was observed in the cases of L1 in methanol and L4 in both THF and methanol. Therefore, there exists a certain unusual hindering factor to keto-enol phototautomerism in the ligand-solvent systems. The sensing property of zinc(II) complexes was explored regarding the effects of substituents in their ligands. It was observed that coordination to the zinc(II) ion led to emission quenching for L1 and L2 while causing an enhancement of fluorescent intensity for L3, L4, L5, and L6. A linear relationship was observed between the emission intensity and the concentration of the zinc ion at the 10(-8) M level. Compared to other zinc compounds in this work, fluorescence enhancement in Z3 and Z4 showed that the methoxyl substituent is favorable for fluorescent enhancement.

Eight imidazole-based compounds 4-methyl-2,6-bis(4,5-diphenyl-1H-imidazol-2-yl)phenol ( A-dp), 2-(1H-phenanthro[9,10-d]imidazol-2-yl)phenol ( B-2H), 5-methoxy-2-(1H-phenanthro[9,10-d]imidazol-2-yl)phenol ( B-2H4M), 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol ( C-3H), 2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-4-methoxyphenol ( C-2H5M), 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-2-methoxyphenol ( C-4H3M), 2-(2-methoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline ( C-2M) and 2-(2,4-dimethoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline ( C-2,4M) were synthesized and characterized by elemental, spectroscopic and X-ray single crystal analyses. Two different crystals of A-dp were grown from ethanol and THF, which revealed that A-dp crystallizes in a monoclinic (P2(1)/c) space group while A-dp·2THF crystallizes in a triclinic (P) space group. A-dp·2THF was devoid of any kind of networks whereas the absence of solvent adducts in the ethanol sample produces 1-dimensional single-stranded helices. Contrary to the reported literature conclusion that 1H-imidazole alkylation should increase the donor strength of the imidazole N-base, protonation–deprotonation equilibrium studies on the compounds suggest that push/pull of electron density on the 2-carbon of the imidazole ring by electron-rich/electron-withdrawing substituents is necessary to influence donor capacity of the N-base electrons. Furthermore, the notable increase in pKa,N: values due to ortho/para-directing methoxy substituents supports the conclusion that electron density push towards the 2-position of the imidazole ring is important for improving N-base donor strengths. DFT calculation results using the B3LYP/6-311+G level of theory were conducted to explore possible theoretical explanations.