Utility In Biological Systems Research Articles

Pyridazine (1, 2-diazine): A Versatile Pharmacophore Known for its Utility in Biological Systems

: The present review describes the biological essence of pyridazine scaffold. Around 142 biologically potential pyridazine entities are gathered in a pile from documented literature. Some of them are commercially available drugs, few are naturally occurring pyridazine compounds, and a wide variety of compounds containing pyridazine moiety are biologically tested, and some are under clinical trials. Rather than collecting large quantities of data, an attempt is made to compile valuable entities. However, efforts have been made to compile the maximum literature in brief. The main motto of this review is to provide a combination of therapeutically active pyridazine containing compounds for further drug design, discovery, and development to contribute to future medicinal chemistry. Our approach is to bring the most biologically potent pyridazine derivatives to medicinal chemists, biologists, pharmacists, and organic chemists. The present work encompasses the literature from 2000-2022 from different and authentic sources. The work is divided according to the bioactive nature of pyridazine nucleus.

Preparation and mechanism study of hydrogen bond induced enhanced composited gelatin microsphere probe

Fluorescent probes offer rapid and efficient detection of metal ions. However, their properties, including high biotoxicity and low detection limits, often limit their utility in biological systems. In this study, we used a microfluidic approach to fabricate photocrosslinked gelatin microspheres with a micropore, providing a straightforward method for loading fluorescent probes into these microspheres based on the adsorption effect and hydrogen bonding interaction. The gelatin microsphere loaded probes, GelMA/TPA-DAP and GelMA/TPA-ISO-HNO were designed and obtained. The results show that these probes exhibit obviously low biotoxicity compared to the original molecular probes TPA-DAP and TPA-ISO-HNO. Simultaneously, it is found that GelMA/TPA-DAP and GelMA/TPA-ISO-HNO have better detection sensitivity, the detection limits are 35.4 nM for Cu2+, 16.5 nM for Co2+ and 20.5 nM for Ni2+ for GelMA/TPA-DAP probe. Compared to the original TPA-DAP they are improved by 37.2 %, 26.3 % and 22.6 % respectively. The corresponding coordination constants were 10.8 × 105, 4.11×105 and 6.04×105, which is larger than homologous TPA-DAP. Similar results were also verified in the GelMA/TPA-ISO-HNO probe. The mechanism was investigated in detail by theoretical simulations and advanced spectral analysis. The density functional theory (DFT) simulations show that the probes are anchored inside the microspheres and the molecular structure is modified due to the hydrogen bonding interaction between the microsphere and the molecular probe, which makes GelMA/TPA-DAP exhibit stronger coordination capacity with metal ions than homologous TPA-DAP. In addition, the adsorption effect also provided some synergistic enhancement contribution. Meanwhile, cellular experiments have also shown that the composite microspheres can improve the biocompatibility of the probe and will provide a wider range of applications towards bioassay. This simple and effective method will provide a convenient way to improve the performance of fluorescent probes and their biological applications.

Enhanced electronic absorption and solubility of Mammeigin in aqueous micelles and protein aggregate solutions compared to water

The physicochemical properties of plant polyphenol Mammeigin (MMG) from Mesua ferrea, upon interactions with carrier molecules like surfactants and Hen Egg-White Lysozyme (HEWL) aggregates were investigated using UV–Vis and Fluorescence spectroscopy; and Zeta potential (ZP) measurements in aqueous solutions. The role of surfactant charge on the interactions of MMG was studied using anionic Sodium Dodecyl Sulfate (SDS), cationic Cetyltrimethylammonium Bromide (CTAB), and neutral Tween 20 (T20). It was observed that ionic surfactants offered more stability to the system, which was enhanced in the presence of salt at physiological concentration and lower amounts of surfactant. The environment of MMG in these micelles was proposed to be partially semi-polar in nature based on solvent studies in organic and binary solvent systems. A similar favorable environment was found in early and partially exposed aggregates of HEWL at pH 2 and pH 9 respectively, which significantly diminished at later stages of aggregation and fibrillation at pH 2. With growing interest in plant polyphenols as bioactive, a major challenge for their utility in biological systems is the aqueous insolubility and thus, research in the field of drug/compound delivery is expanding. Our study could provide insights for developing better molecular carriers and formulations of MMG at physiological conditions for therapeutic applications with improved efficacy.

Copper-Free Click Enabled Triazabutadiene for Bioorthogonal Protein Functionalization.

Aryl diazonium ions have long been used in bioconjugation due to their reactivity toward electron-rich aryl residues, such as tyrosine. However, their utility in biological systems has been restricted due to the requirement of harsh conditions for their generation in situ, as well as limited hydrolytic stability. Previous work describing a scaffold known as triazabutadiene (TBD) has shown the ability to protect aryl diazonium ions allowing for increased synthetic utility, as well as triggered release under biologically relevant conditions. Herein, we describe the synthesis and application of a novel TBD, capable of installation of a cyclooctyne on protein surfaces for later use of copper-free click reactions involving functional azides. The probe shows efficient protein labeling across a wide pH range that can be accomplished in a convenient and timely manner. Orthogonality of the cyclooctyne modification was showcased by labeling a model protein in the presence of hen egg proteins, using an azide-containing fluorophore. We further confirmed that the azobenzene modification can be cleaved using sodium dithionite treatment.

Small-Molecule-Based Fluorescent Sensors for Selective Detection of Reactive Oxygen Species in Biological Systems.

Reactive oxygen species (ROS) encompass a collection of intricately linked chemical entities characterized by individually distinct physicochemical properties and biological reactivities. Although excessive ROS generation is well known to underpin disease development, it has become increasingly evident that ROS also play central roles in redox regulation and normal physiology. A major challenge in uncovering the relevant biological mechanisms and deconvoluting the apparently paradoxical roles of distinct ROS in human health and disease lies in the selective and sensitive detection of these transient species in the complex biological milieu. Small-molecule-based fluorescent sensors enable molecular imaging of ROS with great spatial and temporal resolution and have thus been appreciated as excellent tools for aiding discoveries in modern redox biology. We review a selection of state-of-the-art sensors with demonstrated utility in biological systems. By providing a systematic overview based on underlying chemical sensing mechanisms, we wish to highlight the strengths and weaknesses in prior sensor works and propose some guiding principles for the development of future probes.

Bacterial Biofilm As Active Matrix for Catalytic Centers: Electroreduction of Carbon Dioxide

There is constantly growing interest in the electrochemical reduction of CO2 and applying the process of binding the carbon to synthetic fuels production, as well as alcohols, hydrocarbons, aldehydes or carboxylic acids. Because of the stability of the CO2 molecule, its electrocatalytic reduction is characterized by high over-potentials: consequently selective and efficient electrocatalysts are needed. A typical approach to efficient electroreduction of carbon dioxide is the use of metallic catalysts (e.g. Cu, Pd, Pt, Ru), either in heterogeneous and homogeneous reactions. Recently, the alternative for efficient CO2 electroreduction is also utilization of biological systems, including microbial electrocatalysts and whole cell biocatalysts. These systems often utilize microorganisms in a form of bacterial biofilms at the electrode surfaces, to enhance rates of chemical reactions. Biofilms are very stable layers composed of microbes well-adhering to various surfaces. Differentiation in microbial metabolic pathways, associated with the occurrence of different types of enzymes in microbial cells, creates opportunity to catalyze redox processes at ambient conditions, also carbon dioxide electroreduction. Methods for improvements of electrical connection between microbial cells and electrode surfaces are needed, and one of the ideas is to utilize highly porous conductive polymers, which provide good electrical coupling and facilitate immobilization of the cells. Practical bioelectrochemical systems often use also carbon nanotubes together with biological layers due to their capabilities of penetrating microbial structures and improving the overall conductivity. These properties are particularly important in developing biosensors and microbial fuel cells. There has been proposed a hybrid multilayered matrix, composed of polyaniline-supported Yersinia enterocolitica biofilm, multi-walled carbon nanotubes (MWCNTs) and dispersed Pt nanoparticles (nPt) on the top. The underlayer of polymer, biofilm and MWCNTs has been demonstrated to work as highly active assistance for nPt during carbon dioxide electroreduction in neutral electrolyte (phosphate buffer at pH=6.1). Application of the hybrid system allows clear distinction of the CO2-reduction currents from those originating from the hydrogen evolution, unlike the bare nPt dispersed at glassy carbon surface. The result complies with the enhancement effect toward process of carbon dioxide reduction rather than hydrogen evolution. Bacterial biofilm itself is not catalytically active toward reduction of CO2, however its hydrated structure allows water molecules to easily move through it, and permits aqueous electrolyte to flow undisrupted at the electrocatalytic interface. Application of polyaniline can be commentated in terms of improvement and stabilization of the biofilm adherence and utilization of MWCNTs improve charge distribution within the hybrid film. Assessing based on the results of the diagnostic stripping-type voltammetric experiments, carbon monoxide seems to be the main product of CO2-reduction process at the proposed hybrid layer-supported nPt catalyst. However formation of some quantities of formic acid and methanol cannot be excluded.

A series of terpyridine-based zinc(ii) complexes assembled for third-order nonlinear optical responses in the near-infrared region and recognizing lipid membranes.

Two-photon (TP) microscopy has advantages for biological imaging in that it allows deeper tissue-penetration and excellent resolution compared with one-photon (OP) microscopy. Herein, two-photon activated nonlinear optical (NLO) materials, a terpyridine derivative ligand with a donor-acceptor (D-A) model and its corresponding four zinc(ii) complexes (Z1-Z4), were assembled and fully characterized. Based on their systematic photophysical investigations, it was found that the third-order NLO response in the near-infrared (NIR) region was significantly enhanced for the symmetrical complex Z4 compared with the other asymmetric complexes (Z1-Z3). To further explore its utility in biological systems, Z4 was selected as a two-photon probe for cellular lipid membranes, which was confirmed both by two-photon confocal microscopy and transmission electron microscopy (TEM). Furthermore, it was found that the fluorescence intensity was enhanced for complex Z4 with the addition of bioactive liposomes (1 μg mL-1). Its recognition mechanism was demonstrated by experimental methods, as well as molecular modeling calculations. These findings should open a new pathway for functional metal complexes as lipid membrane targeting probes.

Photo-Triggered Click Chemistry for Biological Applications.

In the last decade and a half, numerous bioorthogonal reactions have been developed with a goal to study biological processes in their native environment, i.e., in living cells and animals. Among them, the photo-triggered reactions offer several unique advantages including operational simplicity with the use of light rather than toxic metal catalysts and ligands, and exceptional spatiotemporal control through the application of an appropriate light source with pre-selected wavelength, light intensity and exposure time. While the photoinduced reactions have been studied extensively in materials research, e.g., on macromolecular surface, the adaptation of these reactions for chemical biology applications is still in its infancy. In this chapter, we review the recent efforts in the discovery and optimization the photo-triggered bioorthogonal reactions, with a focus on those that have shown broad utility in biological systems. We discuss in each cases the chemical and mechanistic background, the kinetics of the reactions and the biological applicability together with the limiting factors.

SYNTHESIS, CHARACTERIZATION AND ANTI MICROBIAL STUDIES OF AgNP’S USING PROBIOTICS

Recent researches speak about the utilization of biological systems especially enterobacteri a to synthesize nanoparticles is a novel approach. The present study demonstrates an eco - friendly and low cost protocol for synthesis of silver nano particles using the cell free filtrate of Lactobacillus bulgaricus when supplied with aqueous silver ions. Characterization of silver nanoparticles was done by UV - Visible absorption spectroscopy shows maximum absorption at 420 nm, Transmission electron microscope (TEM) revealed the formation of spherical nanoparticles with size ranging between 40 – 50nm, X - Ray diffraction (XRD) pattern shows spectrum, which reveals the FCC structure of silver nanoparticles. Energy dispersive spectroscope (EDS) analysi s was done using SEM instrument equipped with thermo EDS attachment shows the optical absorption peak at 3kev. Mi crobial nanoparticles showed very strong inhibitory action against Staphylococcus aureus, Staphylococcus albus, & Pseudomonas aeruginosa.

Biosynthesis of Silver Nanoparticles by Fungus Trichoderma Reesei (A Route for Large-Scale Production of AgNPs)

One of the requirements for advancement of nanotechnology are the development of reliable experimental protocols for the synthesis of nanomaterials over a range of biological compositions, sizes and high monodispersity. An attractive possibility of green nanotechnology is to use microorganisms in the syn thesis of nanoparticles. Recently, the utilization of biological systems, especially fungi, has emerged as a novel method for the synthesis of nanoparticles. Nanoparticles are considered as fundamental molecular building blocks for nanotechnology. They are the starting points for preparing many nanostructured materials and devices. In this paper we report the extracellular biosynthesis of silver nanoparticles (AgNPs) by using a fungus named Trichoderma Reesei (also known as Hypocrea jecorina ). In the biosynthesis of AgNPs by this fungus, the fungus mycelium is exposed to the silver nitrate solution. That prompts the fungus to produce enzymes and metabolites for its own survival. In this process the toxic Ag + ions are reduced to the none� toxic metallic AgNPs through the catalytic effect of the extracellular enzyme and metabolites of the fungus. Absorption UVVisible li ght spectroscopy is used to follow up with the reaction process. Fluorescence emission spectroscopy is used to produce detailed information on the progress of reduction of silver nitrate (formation of silver nanoparticles) on the nanosecond timescale. Fourier transform infrared spectroscopy is used for quantitative analyses of the reaction products. Our measurements indicate that extracellular biosynthesis of AgNPs by Trichoderma reesei produces AgNPs with the diameters in the range of 5�50 nm . Trichoderma Reesei is an environmentally friendly fungus, and it is well known for its formation of extracellular enzyme and metabolites in very large amounts, much higher than other fungi. The present process is an excellent candidate for industrial scale production of silver nanoparticles.

Genetic chemistry: production of non-native compounds in yeast

The tools and perspectives that chemists bring to the study of biological systems have yielded very important discoveries and opened many new research possibilities over the years (Hopkins AL: Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 2008, 11:682-690; Lehar J, Stockwell BR, Giaever G, Nislow C: Combination chemical genetics. Nat Chem Biol 2008, 11:674-681. This work describes use of genome level data to discover and understand higher order pleiotropic effects of combinations of drugs). Chemical biology has an ever-growing toolbox that has been expanding its reach into many different aspects of the study and utilization of biological systems (Strombergsson H, Kleywegt G: A chemogenomic view on protein-ligand spaces. BMC Bioinformatics 2009, 10(Suppl 6):S13; Bumpus BB, Evens BS, Thomas PM, Ntai I, Kelleher NI: A proteomics approach to discovering natural products and their biosynthetic pathways. Nat Biotechnol 2009, 27:951-956. This reviews techniques that allow for the identification of biochemical pathways that produce molecules of interest under very specific situations; Altamn KH, Buchner J, Kessler H, Diederich F, Krautler B, Lippard S, Liskamp R, Muller K, Nolan EM, Samori B, et al.: The state of the art of chemical biology. Chembiochem 2009, 10:16-29) including the study and utilization of biological systems in yeast. This review will describe recent successes in the use of yeast for both discovery and production of non-native secondary metabolites focused on pharmaceutically relevant compounds.

A Bayesian maximum entropy reconstruction of stock distribution and inference of stock density from line-transect acoustic-survey data

AbstractWe present a maximum-entropy (MaxEnt) method for inferring stock density and mapping stock distribution from acoustic line-transect data. MaxEnt is founded on the bedrock of probability theory and allows the most efficient possible use of known data in the inference process. The method takes explicit account of spatial correlation in the observed data and seeks to reconstruct a distribution of density across the whole survey area that is both consistent with the observed data and for which the entropy is maximized. The method is iterative and uses the Bayesian approach of evaluating the posterior probability of a candidate solution under the constraint of the observed data to progress towards a converged solution. We apply the method to reconstruct maps of the distribution of Antarctic krill throughout areas 100 × 80 km2. Survey data were integrated at 0.5-km intervals along ten 80-km transects, giving approximately 1600 observed data points. We inferred the krill density for all 32 000 0.5 × 0.5 km2 cells in the area. The method is demanding computationally, but appears to work well even in cases when the distribution of density is highly skewed. The MaxEnt technique has proved to be powerful for reconstructing quantitative images from incomplete and noisy physical data (e.g. radio-telescope data): we suggest that it has utility in biological systems too and could be of benefit to the fisheries-acoustics community, increasing the accuracy of acoustic estimates of stock density and generating better maps of stock distribution.

Environmental control of lipid and biomass production in two diatom species

Biomass and neutral lipid accumulation were examined in Chaetoceros muelleri var. subsalsum and Navicula saprophila using a multivariate, fractional factorial design. Variables included were conductivity, temperature, nitrogen concentration, silicon concentration, time (culture age), and alkalinity. Measured characteristics included nile red fluorescence (as a measure of neutral lipid content) and ash-free dry weight (AFDW). Nitrogen concentration was the variable with the greatest effect on neutral lipid and ash-free dry weight accumulation over the ranges tested. Increasing conductivity in the range examined had a significant, negative impact on neutral lipid accumulation in both of these strains, while increasing alkalinity had a positive effect on lipid and ash-free dry weight in both strains. Experimental designs such as those described here have great potential utility in biological systems with complex interactions.