Mimetic Complex Research Articles

Efficient water-soluble copper(II) complexes with SOD/CO-like activities and the relationship between their structure and activity

Superoxide dismutase is a significant member of the body’s natural antioxidant defense system. It can effectively eliminate superoxide anion free radicals from the body. Based on the functionalized ligand-isonicotinic acid, three copper complexes were successfully developed. The metal centers of complexes 1–3 were highly similar to the active sites of natural superoxide dismutase. It was found that complexes 1–3 exhibited both excellent superoxide dismutase (SOD)-like and catecholase (CO)-like activities at the same time. A model of oxidative stress, induced by hydrogen peroxide, was constructed based on the cytotoxicity test. In this model, the mimetic complex proved to have effective intracellular antioxidant capacity. Combined with the experimental data and DFT, the results showed that the electron acceptance ability and the coordination configuration of the active center of copper ions had important effects on the activity of SOD.

Synthesis, characterization, thermal, theoretical studies, antimicrobial, antioxidant activity, superoxide dismutase-like activity and catalase mimetics of metal(II) complexes derived from sugar and Schiff base

Abstract Scientists are searching for reactive oxygen species, which have been associated with various health issues like heart problems, neurological disorders, inflammation, and aging. Salen complexes have proven to be effective in multiple oxidative stress situations and have been used as catalase and superoxide mimetics. To explore this further, three mixed complexes were synthesized using a Schiff base (salen) and a sugar (d-glucose) with Co(II), Ni(II), and Cu(II) ions. These complexes were then diagnosed by different analytical and spectral techniques. Stoichiometry, stereochemistry, some physical properties, and the method of bonding complexes were measured. Comparisons of the IR and 1HNMR spectra of the ligands with the complexes demonstrated the involvement of the azomethine group of the ligand in the chelation process. The mass spectra and TGA agree with the proposed formula of the complexes, and the conductivity and UV–Vis data supported the octahedral geometry of the complexes, and information was obtained from partial parameter calculations by molecular modeling. The metal complexes exhibited strong antimicrobial and antioxidant properties when compared to standard drugs. The like-superoxide and catalyst mimetic complexes were screened using DPPH ABTS, revealing their effectiveness.

A new species of Neotropiconyttus Kirkaldy (Hemiptera, Reduviidae) in a cacao plantation from the Colombian Napo Province, including a key to species, and taxonomic notes of the genus.

A new species of the genus Neotropiconyttus Kirkaldy, 1909 (Hemiptera: Heteroptera: Reduviidae: Harpactorinae: Harpactorini) is described and illustrated. Neotropiconyttusarmandoi Gamboa & Gil-Santana, sp. nov. represents the first record of the genus for the Province of Napo in Colombia, and the first description of a male individual in the genus. The male specimen representing the new species was collected on a leaf of cacao (Theobromacacao L.-Malvaceae). Its remarkable similarity in external coloration and structure with that of the true bug Monaloniondissimulatum Distant, 1883 (Hemiptera: Miridae) inhabiting cacao agroforestry systems suggests that the new species could be part of a mimetic complex that incorporates phytophagous and predator bugs. Comments and figures of type specimens of Neotropiconyttusalboannulatus (Stål, 1855) and Neotropiconyttusdama (Burmeister, 1838), and a key to the species of the genus are also provided.

Designing and computational analyzing of chimeric long-lasting GLP-1 receptor agonists for type 2 diabetes

Glucagon-like peptide-1 (GLP-1) is an intestinally derived incretin that plays a vital role in engineering the biological circuit involved in treating type 2 diabetes. Exceedingly short half-life (1–2 min) of GLP-1 limits its therapeutic applicability, and the implication of its new variants is under question. Since albumin-binding DARPin as a mimetic molecule has been reported to increase the serum half-life of therapeutic compounds, the interaction of new variants of GLP-1 in fusion with DARPin needs to be examined against the GLP-1 receptor. This study was aimed to design stable and functional fusion proteins consisting of new protease-resistant GLP-1 mutants (mGLP1) genetically fused to DARPin as a critical step toward developing long-acting GLP-1 receptor agonists. The stability and solubility of the engineered fusion proteins were analyzed, and their secondary and tertiary structures were predicted and satisfactorily validated. Molecular dynamics simulation studies revealed that the predicted structures of engineered fusion proteins remained stable throughout the simulation. The relative binding affinity of the engineered fusion proteins' complex with human serum albumin and the GLP-1 receptor individually was assessed using molecular docking analyses. It revealed a higher affinity compared to the interaction of the individual GLP-1 and HSA-binding DARPin with the GLP-1 receptor and human serum albumin, respectively. The present study suggests that engineered fusion proteins can be used as a potential molecule in the treatment of type 2 diabetes, and this study provides insight into further experimental use of mimetic complexes as alternative molecules to be evaluated as new bio-breaks in the engineering of biological circuits in the treatment of type 2 diabetes.

Urea Decomposition Mechanism by Dinuclear Nickel Complexes

Urease is an enzyme containing a dinuclear nickel active center responsible for the hydrolysis of urea into carbon dioxide and ammonia. Interestingly, inorganic models of urease are unable to mimic its mechanism despite their similarities to the enzyme active site. The reason behind the discrepancy in urea decomposition mechanisms between inorganic models and urease is still unknown. To evaluate this factor, we synthesized two bis-nickel complexes, [Ni2L(OAc)] (1) and [Ni2L(Cl)(Et3N)2] (2), based on the Trost bis-Pro-Phenol ligand (L) and encompassing different ligand labilities with coordination geometries similar to the active site of jack bean urease. Both mimetic complexes produced ammonia from urea, (1) and (2), were ten- and four-fold slower than urease, respectively. The presence and importance of several reaction intermediates were evaluated both experimentally and theoretically, indicating the aquo intermediate as a key intermediate, coordinating urea in an outer-sphere manner. Both complexes produced isocyanate, revealing an activated water molecule acting as a base. In addition, the reaction with different substrates indicated the biomimetic complexes were able to hydrolyze isocyanate. Thus, our results indicate that the formation of an outer-sphere complex in the urease analogues might be the reason urease performs a different mechanism.

The conformational space of the SARS-CoV-2 main protease active site loops is determined by ligand binding and interprotomer allostery.

In this study, we characterize two SARS-CoV-2 main protease (Mpro) active site loops that play a role in catalysis using large scale all-atom molecular dynamics simulations. Machine-learning methods are used to identify open and closed states in both the upper and lower loops, as well as an additional intermediate state in the lower loop. In the closed and intermediate states, the positions of the catalytic Cys-His dyad are stabilized, bringing Asp187 into position to mediate charge from a proton transfer during catalysis. Simulations of a protease substrate mimetic complex exhibit an increased frequency of closed and intermediate states and reveals that a substrate binding to one protomer of the homodimer causes its apo partner to more closely resemble the structural ensemble of the bound state. We use dynamic network analysis to reveal the optimal allosteric path between active sites, which travels through a pathway bridged by the N-terminus, providing useful information for the development of potential allosteric inhibitors. This study offers insight into relationships between the flexible loops and the substrate binding in a prime drug target.

Aversive reactions of two invertebrate predators to European red–black insects

AbstractPrey species gain protection by imitating signals of unpalatable models in defensive mimicry. Mimics have been traditionally classified as Batesian (palatable mimic resembling an unpalatable model) or Müllerian (unpalatable mimic resembling a similarly unpalatable model). However, recent studies suggest that rather than discrete categories, the phenomenon of mimicry can be better understood as a continuum. The level of unpalatability of defended prey is a key factor in determining the type of mimetic relationship. Herein, we used insects (ladybugs and true bugs) from a putative European “red–black” mimetic complex as experimental models of defended species and crickets as a control prey. We offered the prey to two species of sympatric invertebrate predators (praying mantis and spider) and video recorded the interactions. We tested three alternative hypotheses, namely (i) the three red–black species tested are similarly defended against both predators; (ii) some red–black species are better defended than others against both predator species, and (iii) the effectiveness of the red–black species defenses is predator dependent. Both predators attacked all prey types with a similar frequency. But while all three red–black species similarly elicited aversive behaviors in spiders, the mantises' aversive reactions varied depending on the prey species. Our results provide support to the third hypothesis, suggesting that the same prey species can fall into different parts of the spectrum of palatability–unpalatability depending on the type of predator.

Molecular Identification of an Avian Predator of Mimetic Salamanders

Natural field observations of salamander predation are uncommon, in some cases limiting the ability of scientists to study the evolution of toxicity, aposematism, and mimicry in these amphibians. Here, we document field observations of recently depredated salamanders: 1 Pseudotriton ruber (Red Salamander) and 2 Gyrinophilus porphyriticus (Spring Salamander), members of a putative Müllerian mimetic complex involving Notophthalmus viridescens (Eastern Newt). We used molecular methods to identify the likely avian predator of the Spring Salamanders and underscore the opportunities for future research enabled by the pairing of traditional natural history with modern molecular techniques.

Symptomic Mimicry Between SARS-CoV-2 and the Common Cold Complex

The recent changes in COVID-19 symptoms suggest convergent evolution of respiratory diseases. This process is analogous to the emergence of animal mimetic complexes and complements previously identified types of mimicry. A novel pathogen might go unnoticed or insufficiently counteracted if it resembles a disease that the host already faced on multiple occasions, which creates a selective pressure towards a typical symptomic phonotype. In short, the reason why so many unrelated pathogens cause similar symptoms may correspond to the reasons that drove the evolution of the ‘warning’ wasp-like colouration in various insect species.

Insights into the binding of arginine to adenosine phosphate from mimetic complexes.

The amino acid arginine plays a key role in the interaction of proteins with adenosine phosphates, as its protonated guanidinium side group is capable of building multipodal H-bonding interactions with the oxygen atoms of the phosphate, phosphoester and ribose moieties and with the nitrogen atoms of adenine. Protein interactions often take place in competition with other ionic species, typically metal cations, which are prone to build concerted coordination arrangements with the same centers of negative charge as guanidinium. We report on a vibrational spectroscopy and computational investigation of a positively charged ternary complex formed by adenosine monophosphate (AMP) with methyl guanidinium and Na+. Following a bottom-up approach, an analogous complex with ribose phosphate is characterized as well, which serves to assess the individual role of the phosphate, sugar and adenine moieties in the binding process and to compare, within a single complex, the interactions associated with diffuse versus localized charge distributions of guanidinium and the alkali cation, respectively. The results indicate that Na+ is preferentially hosted in a semi-rigid pocket formed by the phosphoester-adenosine backbone of AMP and displaces guanidinium to a peripheral binding to the phosphate anionic end group. This suggests that the control of the salt concentration may constitute an effective route to modulate protein-AMP complexation.

Wariness to colour patterns: birds versus European red‐and‐black insects

1. A mimetic complex of red‐and‐black insects is proposed to occur in Central Europe.2. In our study, we tested in isolation the importance of a colour pattern as the main factor responsible for the predator avoidance of the members of this putative mimetic complex by transferring the patterns of seven European red‐and‐black insects onto a palatable prey using paper stickers. Wild‐caught adult great tits (Parus major) were used as the predators.3. In general, the response of the tested birds to palatable prey carrying a conspicuous pattern differed from their responses to the real insect species demonstrated in previous studies.4. The birds avoided the pattern of Pyrrhocoris apterus most often, putatively because of their rich individual experience with the real insect from the wild, since it is the most common amongst our chosen species. Other patterns were attacked similarly to the control, inconspicuous roach pattern. Obviously, these patterns did not discourage the birds from making a closer inspection of the offered prey and revealing the edible cockroach hidden underneath the coloured paper sticker.5. We show that the method of transferring aposematic colour patterns to edible prey has substantial limitations when testing how predators generalise colour patterns within the mimetic complex.

Being a bright snake: Testing aposematism and mimicry in a neotropical forest

AbstractBased on color patterns and behavioral similarities, venomous coral snake Micrurus corallinus (Elapidae) may act as a model for two polymorphic species, Erythrolamprus aesculapii (Dipsadidae) and Micrurus decoratus (Elapidae). Plasticine replicas were used to investigate the aposematism of these coloration patterns and whether these species may be part of mimetic complexes in two Atlantic Forest localities in Southeast Brazil. Coral replicas were more avoided when set upon a white background, evincing that the pattern may act aposematically in contrast with light substrates. Birds attacked all four patterns equally during the mimicry experiments. Birds of prey, known to be effective in predating snakes, are quite abundant in the study areas, which may have led to this lack of avoidance. Accordingly, they predated more adult‐sized replicas, which could be more dangerous. Interestingly, opossum avoided the Micrurus corallinus and Erythrolamprus aesculapii replicas that resembled the model. This suggests that opportunistic predators, as the opossum may be important selective agents in mimicry complexes.Abstract in Portuguese is available with online material.

Introgresión genética y especiación de Heliconius hecalesia (Hewitson [1854]) (Lepidoptera: Heliconiinae) en zonas de hibridación en el occidente de Colombia

aclarar el estatus taxonómico de Heliconius gynaesia y H. longarena dentro del grupo de “hecalesia” y conocer la delimitación genética y geográfica de las subespecies. Metodología: se realizaron observaciones directas en campo en las áreas de distribución de las diferentes subespecies de H. hecalesia en Colombia. Para comparar los diferentes morfotipos se realizaron cruces genéticos en condiciones de invernadero entre las poblaciones de H. hecalesia hecalesia del Magdalena medio, con las poblaciones de H. hecalesia longarena de la región del Chocó biogeográfico en el occidente de Colombia. Resultado: se presentan y discuten los cruces genéticos de los diferentes fenotipos obtenidos de un mismo cruce parental y retrocruce, del cual fue posible reconstruir las formas gynaesia y ernestus, que son consistentes con el patrón de coloración a los especímenes tipo. Todos los fenotipos estudiados están involucrados en un nuevo complejo mimético con Tithorea tarricina y Neruda godmani, el cual es descrito en este artículo. El aislamiento reproductivo de las poblaciones del suroccidente de Colombia que se manifiesta mediante esterilidad hibrida e inviabilidad en los cruces artificiales, proporciona una fuerte evidencia y soporte para el reconocimiento de H. longarena n. comb como una buena especie como parte de este estudio. Se coloca a H. hecalesia gynaesia en sinonimia n. syn con H. longarena por tratarse de un híbrido natural.

The Role of the Cysteine Fragments of the Nickel Binding Loop in the Activity of the Ni(II)-Containing SOD Enzyme.

Detailed equilibrium, spectroscopic, and SOD activity studies are reported on nickel(II) complexes formed with the N-terminally free HHDLPCGVY-NH2 (NiSODHH) and HCDLPHGVY-NH2 (NiSODHC) peptides mimicking the nickel binding loop in NiSOD. In these model peptides, cysteine was incorporated in different positions in order to gain better insight into the role of the cysteine residues in NiSOD. The results are compared with those obtained with the wild-type fragment of NiSOD. The complex formation equilibria of nickel(II) with the two peptides exhibit different features. In the case of NiSODHH, the ligand field of the (NH2,NIm,NIm,S-) donor set is not strong enough to cause spin pairing and an octahedral paramagnetic complex is formed under physiological conditions. In contrast, NiSODHC forms a square-planar diamagnetic complex with (NH2,N-,S-,NIm) donors which exhibits remarkable SOD activity. Our results unambiguously prove that the presence of cysteine in the secondary position of the peptide chain is crucial to establish the square-planar geometry in the reduced form of NiSOD, while the distant cysteine affects the redox properties of the Ni(II)/Ni(III) couple. Compared to the model systems, the Ni(II) complex with the wild-type fragment of NiSOD exhibits superior SOD activity. This confirms that both cysteinyl residues are essential in the efficient degradation of superoxide ion. The enzyme mimetic complexes are also capable of assisting the decomposition of superoxide ion; however, they show considerably smaller catalytic activity due to the absence of one of the cysteine residues.

A luminescent lipid mimetic iridium(III) N-heterocyclic carbene complex for membrane labelling

Labelling phospholipid membranes with luminophores without altering the biophysical characteristics of the system is particularly challenging due to the small size of the phospholipid molecules and the sensitivity of membrane properties to the presence of fused heterocyclic molecules. Here the design and synthesis of a luminescent lipid mimetic Ir(III) N-heterocyclic carbene complex of the form [Ir(ppy)2(C^N)] (where ppy = 2-(phenyl)-pyridine and C^N is a N-heterocyclic carbene ligand) conjugated to stearic acid is described. This complex was synthesised by the reaction of an acetate functionalised Ir(III) precursor complex with tert-butyl N-(2-aminoethyl)carbamate (mono-BOC protected ethylene diamine) and after deprotection of the amine group this complex was coupled to stearic acid using the peptide coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The photophysical properties of the synthesised complexes were evaluated and they showed blue-green luminescence in the range of 514–520 nm. Fluorescence microscopy studies showed that the lipid mimetic complex successfully incorporated into liposomes composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), while dynamic light scattering (DLS) and differential scanning calorimetry (DSC) studies showed that the complex had negligible influence on the biophysical properties of the liposomes.

Phenotypic analysis of aposematic conoderine weevils (Coleoptera: Curculionidae: Conoderinae) supports the existence of three large mimicry complexes

AbstractThe Conoderinae (Coleoptera: Curculionidae) are one of the most distinctive Neotropical weevil groups in behaviour and appearance, attracting numerous hypotheses regarding the evolution and function of widespread apparent mimetic convergence. Conoderines have a poorly documented natural history, and a large fraction of the diversity of the group remains undescribed, presenting challenges to their study. In this analysis, 128 species of conoderine weevils previously or herein hypothesized to belong to three mimicry complexes are analysed in the first quantitative test of conoderine mimicry. Fifteen continuous and categorical characters describing the size, shape and coloration of these weevils were analysed using non-metric multidimensional scaling while statistically testing the resulting clusters in ordination space. Three similar, putatively mimetic complexes are recognized: (1) the ‘red-eyed fly’ complex of weevils, which are hypothesized to be evasively mimetic on various species of red-eyed flies; (2) the ‘striped/spotted’ complex, composed of weevils with a brightly coloured pronotum and red to white elytral stripes or spots; and (3) the ‘shiny blue’ complex of species with iridescent blue to blue–green pronotal scales. Each of these groups covers a wide geographical distribution and has evolved independently in multiple genera, although the red-eyed fly complex appears to be both the most species rich and widely distributed phylogenetically. Groupings were found to be statistically significant, although variation within each group suggests that the similarity in appearance of species in each group could be attributable to independent convergence on different, but phenotypically similar, models. Several avenues for future research on conoderine mimicry are discussed.

Dual Inhibition of Klebsiella pneumoniae and Pseudomonas aeruginosa Iron Metabolism Using Gallium Porphyrin and Gallium Nitrate

Iron- and heme-uptake pathways and metabolism are promising targets for the development of new antimicrobial agents, as their disruption would lead to nutritional iron starvation and inhibition of bacterial growth. Salts of gallium(III) (Ga), an iron mimetic metal, disrupt iron-dependent biological processes by binding iron-utilizing proteins and competing with iron for uptake by bacterial siderophore-mediated iron uptake systems. Ga porphyrins, heme mimetic complexes, disrupt heme-utilizing hemoproteins. Because Ga(NO3)3 and Ga porphyrin disrupt different pathways of bacterial ion acquisition and utilization, we hypothesized that if used in combination, they would result in enhanced antimicrobial activity. Antimicrobial activity of Ga porphyrins (Ga protoporphyrin, GaPP, or Ga mesoporphyrin, GaMP) alone and in combination with Ga(NO3)3 were evaluated against Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) under iron-limited conditions. The Ga porphyrin/Ga(NO3)3 combination demonstrated substantial synergism against K. pneumoniae, P. aeruginosa, and MRSA. Time-kill assays revealed that the synergistic combination of GaPP/Ga(NO3)3 was bacteriostatic against K. pneumoniae and MRSA and bactericidal against P. aeruginosa. The GaPP/Ga(NO3)3 combination significantly disrupted K. pneumoniae and P. aeruginosa biofilms on plasma-coated surfaces and increased the survival of Caenorhabditis elegans infected with K. pneumoniae or P. aeruginosa. When assessing the antibacterial activity of the Ga(III)/antibiotic combinations, GaPP/colistin and Ga(NO3)3/colistin combinations also showed synergistic activity against K. pneumoniae and P. aeruginosa. Our results demonstrate that GaPP and Ga(NO3)3 have significant synergistic effects against several important human bacterial pathogens through dual inhibition of iron and heme metabolism.

Eating with the enemy? Mimic complex between a stingless bee and assassin bugs

In this study, we record for the first time the genus Notocyrtus (Heteroptera, Reduviidae) from Argentina based on three species: Notocyrtus dorsalis (Gray), Notocyrtus dispersus Carvalho & Costa, and Notocyrtus foveatus Stål. We also describe and illustrate a mimetic complex comprising the three Notocyrtus species and Tetragona clavipes (Fabricius) (Apidae, Meliponini), that were collected on Bahuinia forficata Link (Leguminosae: Caesalpinioideae). We include biological comments on the plant-reduvid-bee interaction and hypothesize about the functionality of the mimetic complex described.

Application of metal complexes as biomimetic catalysts on glycerol oxidation

Two biomimetic complexes were evaluated as catalysts in the H2O2 mediated oxidation of glycerol, namely a peroxidase mimetic Fe(III) protoporphyrin complex (hematin) and the superoxide-dismutase mimetic complex of Mn(III) with 1,3-bis(5-sulphonatesalycilidenamino) propane (MnL−). Catalysis was targeted to glyceraldehyde since antimicrobial power was proved for it. Glyceraldehyde evolved at a higher rate than the uncatalyzed reaction only with hematin acid treated solutions and kinetics were typical of a radical mechanism. Nonetheless, glycerol conversions were low. H2O2 bleached hematin and the immobilization on a porous matrix could not prevent this. Meanwhile, the catalatic activity of hematin was high but its peroxidatic activity was inhibited at pH > 8. Thus, the coordination of hematin compound I to H2O2 over glycerol may be the preferred route with the accumulation of peroxy radicals, able to degrade the porphyrinic ring -with probable iron releasing- but also contributing to glycerol oxidation. On the other hand, a prompt decay with time of the catalatic and peroxidatic activities of MnL− was observed, which was improved by the addition of dimethylsulfoxide (DMSO), dimethylformamide (DMF) or acetone to the basic buffer system. Finally, EPR spectroscopy of MnL− supported the hypothesis of the formation of an inactive bis-oxo-bridged Mn(IV)Mn(IV) dimer upon addition of H2O2.

Molecular Recognition of a Thomsen-Friedenreich Antigen Mimetic Targeting Human Galectin-3.

Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90 % of adenocarcinomas. Additionally, the binding of the TF antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction have the potential to prevent cancer metastasis. A multidisciplinary approach combining the optimized synthesis of a TF antigen mimetic with NMR, X-ray crystallography methods, and isothermal titration calorimetry assays was used to unravel the molecular structural details that govern the Gal-3/TF mimetic interaction. The TF mimetic has a binding affinity for Gal-3 similar to that of the TF natural antigen and retains the binding epitope and bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective, a decrease in the enthalpic contribution was observed for the Gal-3/TF mimetic complex; however, this behavior is compensated by a favorable gain in entropy. From a structural perspective, these results establish our TF mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and for likely use in hampering Gal-3-mediated cancer cell adhesion and metastasis.