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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.

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.

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.

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.

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 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.