scholarly journals 4-Dialkylamino-2,5-dihydroimidazol-1-oxyls with Functional Groups at the Position 2 and at the Exocyclic Nitrogen: The pH-Sensitive Spin Labels

Gels ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Dmitrii G. Trofimov ◽  
Yuri I. Glazachev ◽  
Artem A. Gorodetsky ◽  
Denis A. Komarov ◽  
Tatyana V. Rybalova ◽  
...  
Keyword(s):  
Functional Groups ◽  
Electrostatic Interactions ◽  
Specific Binding ◽  
Ph Sensitive ◽  
Epr Spectra ◽  
Spin Labels ◽  
Adsorption Activity ◽  
Ph Variation ◽  
Ph Changes ◽  
Vital Functions

Local acidity and electrostatic interactions are associated both with catalytic properties and the adsorption activity of various materials, and with the vital functions of biomolecules. The observation of acid–base equilibria in stable free radicals using EPR spectroscopy represents a convenient method for monitoring pH changes and the investigation of surface electrostatics, the advantages of which are especially evident in opaque and turbid samples and in porous materials such as xerogels. Imidazoline nitroxides are the most commonly used pH-sensitive spin probes and labels due to the high sensitivity of the parameters of the EPR spectra to pH changes, their small size, and their well-developed chemistry. In this work, several new derivatives of 4-(N,N-dialkylamino)-2,5-dihydrioimidazol-1-oxyl, with functional groups suitable for specific binding, were synthesized. The dependence of the parameters of their EPR spectra on pH was studied. Several showed a pKa close to 7.4, following the pH changes in a normal physiological range, and some demonstrated a monotonous change of the hyperfine coupling constant by 0.14 mT upon pH variation by four units.

Dynamic Shaping of Cellular Membranes by Phospholipids and Membrane-Deforming Proteins

2014 ◽  
Vol 94 (4) ◽  
pp. 1219-1248 ◽  
Author(s):  
Shiro Suetsugu ◽  
Shusaku Kurisu ◽  
Tadaomi Takenawa
Keyword(s):  
Plasma Membrane ◽  
Electrostatic Interactions ◽  
Specific Binding ◽  
Membrane Curvature ◽  
Coated Pits ◽  
Cytosolic Proteins ◽  
Anionic Phospholipids ◽  
Vital Functions ◽  
Submicron Scale ◽  
Micro Structures

All cellular compartments are separated from the external environment by a membrane, which consists of a lipid bilayer. Subcellular structures, including clathrin-coated pits, caveolae, filopodia, lamellipodia, podosomes, and other intracellular membrane systems, are molded into their specific submicron-scale shapes through various mechanisms. Cells construct their micro-structures on plasma membrane and execute vital functions for life, such as cell migration, cell division, endocytosis, exocytosis, and cytoskeletal regulation. The plasma membrane, rich in anionic phospholipids, utilizes the electrostatic nature of the lipids, specifically the phosphoinositides, to form interactions with cytosolic proteins. These cytosolic proteins have three modes of interaction: 1) electrostatic interaction through unstructured polycationic regions, 2) through structured phosphoinositide-specific binding domains, and 3) through structured domains that bind the membrane without specificity for particular phospholipid. Among the structured domains, there are several that have membrane-deforming activity, which is essential for the formation of concave or convex membrane curvature. These domains include the amphipathic helix, which deforms the membrane by hemi-insertion of the helix with both hydrophobic and electrostatic interactions, and/or the BAR domain superfamily, known to use their positively charged, curved structural surface to deform membranes. Below the membrane, actin filaments support the micro-structures through interactions with several BAR proteins as well as other scaffold proteins, resulting in outward and inward membrane micro-structure formation. Here, we describe the characteristics of phospholipids, and the mechanisms utilized by phosphoinositides to regulate cellular events. We then summarize the precise mechanisms underlying the construction of membrane micro-structures and their involvements in physiological and pathological processes.

A Mechanism for Reversibly Pausing a Self-Immolation Cascade in Response to pH Changes

2019 ◽  
Author(s):  
Derrick Roberts ◽  
Ben S. Pilgrim ◽  
Tristan Dell ◽  
Molly Stevens
Keyword(s):  
Local Environment ◽  
Chemical Signals ◽  
Ph Sensitive ◽  
First Report ◽  
Ph Changes ◽  
Self Immolation

We describe the first report of a self-immolation cascade that can be reversibly paused and reactivated in response to pH changes. This system employs a triazole-based self-immolative linker, which expresses a pH-sensitive intermediate during its elimination sequence. This allows the system to respond to pH cues within its local environment, thus establishing a new way to gate self-immolative release using fluctuating or transient chemical signals.<br>

Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

2018 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Alejandro Lara ◽  
David L. Mobley ◽  
Toon Vestraelen ◽  
Adelio R Matamala ◽  
...  
Keyword(s):  
Force Field ◽  
Functional Groups ◽  
Electrostatic Interactions ◽  
Organic Molecules ◽  
Force Fields ◽  
Chemical Elements ◽  
Atomic Charges ◽  
Free Energies ◽  
Molecular Systems ◽  
Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

A stochastic reaction-diffusion model for protein aggregation on DNA

2017 ◽  
Vol 28 (08) ◽  
pp. 1750102 ◽  
Author(s):  
Nikolaos K. Voulgarakis
Keyword(s):  
Electrostatic Interactions ◽  
Reaction Diffusion ◽  
Control Parameters ◽  
Physical Mechanisms ◽  
Softening Behavior ◽  
Vital Functions ◽  
Reaction Diffusion Model ◽  
Proposed Model ◽  
Negative Supercoiling ◽  
Stochastic Reaction

Vital functions of DNA, such as transcription and packaging, depend on the proper clustering of proteins on the double strand. The present study investigates how the interplay between DNA allostery and electrostatic interactions affects protein clustering. The statistical analysis of a simple but transparent computational model reveals two major consequences of this interplay. First, depending on the protein and salt concentration, protein filaments exhibit a bimodal DNA stiffening and softening behavior. Second, within a certain domain of the control parameters, electrostatic interactions can cause energetic frustration that forces proteins to assemble in rigid spiral configurations. Such spiral filaments might trigger both positive and negative supercoiling, which can ultimately promote gene compaction and regulate the promoter. It has been experimentally shown that bacterial histone-like proteins assemble in similar spiral patterns and/or exhibit the same bimodal behavior. The proposed model can, thus, provide computational insights into the physical mechanisms used by proteins to control the mechanical properties of the DNA.

scholarly journals A Complete Assessment of Dopamine Receptor-Ligand Interactions through Computational Methods

2019 ◽  
Author(s):  
Beatriz Bueschbell ◽  
Carlos A.V. Barreto ◽  
Antonio J. Preto ◽  
Anke C. Schiedel ◽  
Irina S. Moreira
Keyword(s):  
Dopamine Receptor ◽  
Electrostatic Interactions ◽  
Specific Binding ◽  
Binding Pocket ◽  
Binding Mode ◽  
Receptor Subtypes ◽  
Receptor Ligand ◽  
Pi Stacking ◽  
Ligand Interactions ◽  
New Treatments

Background: Selectively targeting dopamine receptors has been a persistent challenge in the last years for the development of new treatments to combat the large variety of diseases evolving these receptors. Although, several drugs have been successfully brought to market, the subtype-specific binding mode on a molecular basis has not been fully elucidated. Methods: Homology modeling and molecular dynamics were applied to construct robust conformational models of all dopamine receptor subtypes (D1-like and D2-like receptors). Fifteen structurally diverse ligands were docked to these models. Contacts at the binding pocket were fully described in order to reveal new structural findings responsible for DR sub-type specificity. Results: We showed that the number of conformations for a receptor:ligand complex was associated to unspecific interactions &gt; 2.5 &Aring; and hydrophobic contacts, while the decoys binding energy was influenced by specific electrostatic interactions. Known residues such as 3.32Asp, the serine microdomain and the aromatic microdomain were found interacting in a variety of modes (HB, SB, &pi;-stacking). Purposed TM2-TM3-TM7 microdomain was found to form a hydrophobic network involving Orthosteric Binding Pocket (OBP) and Secondary Binding Pocket (SBP). T-stacking interactions revealed as especially relevant for some large ligands such as apomorphine, risperidone or aripiprazole. Conclusions: This in silico approach was successful in showing known receptor-ligand interactions as well as in determining unique combinations of interactions, key for the design of more specific ligands.

Recent Progress in Stimuli Responsive Intelligent Nano Scale Drug Delivery Systems: A special focus towards pH sensitive systems

2021 ◽  
Vol 22 ◽  
Author(s):  
Vaidevi Sethuraman ◽  
Kumar Janakiraman ◽  
Venkateshwaran Krishnaswami ◽  
Ruckmani Kandasamy
Keyword(s):  
Drug Delivery ◽  
Cancer Treatment ◽  
Drug Delivery Systems ◽  
Disease Diagnosis ◽  
Delivery Systems ◽  
Ph Sensitive ◽  
Special Focus ◽  
Stimuli Responsive ◽  
Ph Variation ◽  
Responsive Systems

Abstract: Stimuli responsive nanocarriers are gaining much attention due to its versatile multifunctional activities including disease diagnosis and treatment. Recently, clinical applications of nano drug delivery systems for cancer treatment make a considerable challenge due to its limited cellular uptake, low bioavailability, poor targetability, stability issues, and unfavourable pharmacokinetics. To overcome these issues researchers are focussing on stimuli responsive systems. Nano carriers elicit its role through endogenous (pH, temperature, enzyme and redox) or exogenous (temperature, light, magnetic field, ultrasound) stimulus. These systems were designed to overcome the shortcomings such as non-specificity and toxicity associated with the conventional drug delivery systems. The pH variation between healthy cells and tumor microenvironment creates a platform towards the generation of pH sensitive nano delivery systems. Herein, we propose to present an overview of various internal and external stimuli responsive behavior based drug delivery systems. Herein the present review will focus specifically on the significance of various pH- responsive nanomaterials such as polymeric nanoparticles, nano micelles, inorganic based pH sensitive drug delivery carriers such as calcium phosphate nanoparticles, and carbon dots in cancer treatment. Moreover, this review elaborates the recent findings on pH based stimuli responsive drug delivery system with special emphasis towards our reported stimuli responsive systems for cancer treatment.

scholarly journals pH and Redox Induced Color Changes in Protein Crystals Suffused with Dyes

Crystals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 126 ◽  
Author(s):  
Alexander McPherson
Keyword(s):  
Ascorbic Acid ◽  
Redox Potential ◽  
Mother Liquor ◽  
Ph Sensitive ◽  
Protein Crystals ◽  
Ph Changes ◽  
Color Changes ◽  
Chemical Factors ◽  
Diffusion Rates ◽  
Over Time

Protein crystals, otherwise usually colorless, can be stained a variety of hues by saturating them with dyes, by diffusion from the mother liquor or co-crystallization. The colors assumed by dyes are a function of chemical factors, particularly pH and redox potential. Protein crystals saturated with a pH sensitive dye, initially at one pH, can be exposed to the mother liquor at a second pH and the crystal will change color over time as H3O+ ions diffuse through the crystal. This allows diffusion rates of H3O+ through the crystal to be measured. Diffusion fronts are often clearly delineated. Similar experiments can be carried out with redox sensitive dyes by adding reductants, such as ascorbic acid or dithionite, or oxidants such as H2O2, to the crystal’s mother liquor. Presented here are a number of experiments using pH or redox sensitive dye-saturated protein crystals, and some experiments using double dye, sequential redox–pH changes.

scholarly journals Exploration of an Extracellular Polymeric Substance from Earthworm Gut Bacterium (Bacillus licheniformis) for Bioflocculation and Heavy Metal Removal Potential

2020 ◽  
Vol 10 (1) ◽  
pp. 349 ◽  
Author(s):  
Jayanta Kumar Biswas ◽  
Anurupa Banerjee ◽  
Binoy Sarkar ◽  
Dibyendu Sarkar ◽  
Santosh Kumar Sarkar ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Functional Groups ◽  
Bacillus Licheniformis ◽  
Extracellular Polymeric Substance ◽  
Electrostatic Interactions ◽  
Metal Removal ◽  
Metal Sorption ◽  
Polymeric Substance ◽  
13C Nuclear Magnetic Resonance ◽  
Earthworm Gut

The present study shows the potential of an extracellular polymeric substance (EPS) produced by Bacillus licheniformis strain KX657843 isolated from earthworm (Metaphire posthuma) gut in the sorption of Cu(II) and Zn(II) and in flocculation. After harvesting bacterial cells from sucrose supplemented denitrifying culture medium, the EPS was extracted following ethanolic extraction method. The Fourier Transform Infrared Spectroscopy (FTIR) and 1H and 13C Nuclear Magnetic Resonance (NMR) of EPS revealed its functional groups, electronegative constituents, unsaturated carbon, and carbonyl groups. The negatively charged functional groups of carbohydrates and protein moiety of the EPS endowed it with heavy metal binding capacity through electrostatic interactions. The highest flocculation activity (83%) of EPS was observed at 4 mg L−1 and pH 11. The metal sorption by EPS increased with increasing pH. At pH 8, the EPS was able to remove 86 and 81% Cu(II) and Zn(II), respectively, from a 25 mg L−1 metal solution. 94.8% of both the metals at 25 mg L−1 metal solutions were removed by EPS at EPS concentration of 100 mg L−1. From Langmuir isotherm model, the maximum sorption capacities of EPS were calculated to be 58.82 mg g−1 for Cu(II) and 52.45 mg g−1 for Zn(II). The bacterial EPS showed encouraging flocculating and metal sorption properties. The potential to remove Cu(II) and Zn(II) implies that the EPS obtained from the earthworm gut bacteria can be used as an effective agent for environmental remediation of heavy metals and in bioflocculation.

scholarly journals A Theoretical Study of the Adsorption Process of B-aflatoxins Using Pyracantha koidzumii (Hayata) Rehder Biomasses

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 283
Author(s):  
Abraham Méndez-Albores ◽  
René Escobedo-González ◽  
Juan Manuel Aceves-Hernández ◽  
Perla García-Casillas ◽  
María Inés Nicolás-Vázquez ◽  
...  
Keyword(s):  
Functional Groups ◽  
Electrostatic Interactions ◽  
Density Functional ◽  
Ph Value ◽  
Theoretical Calculations ◽  
Basis Set ◽  
Hydroxyl Group ◽  
Biosorption Process

Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B1 (AFB1) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass; these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB1 biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB1 molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB1 molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB1 adsorption when using in vitro and in vivo trials.

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