scholarly journals Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands

2022 ◽  
Vol 9 ◽  
Author(s):  
Dinorah Gambino ◽  
Lucía Otero
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Organic Ligand ◽  
Chemical Species ◽  
Organometallic Compounds ◽  
New Drugs ◽  
Attractive Option ◽  
Bioactive Ligands ◽  
Trypanosomatid Parasites ◽  
Protozoan Infections

Human African Trypanosomiasis (HAT), Chagas disease or American Trypanosomiasis (CD), and leishmaniases are protozoan infections produced by trypanosomatid parasites belonging to the kinetoplastid order and they constitute an urgent global health problem. In fact, there is an urgent need of more efficient and less toxic chemotherapy for these diseases. Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs and, in particular, antiparasitic ones. In this sense, one of the main strategies for the design of metal-based antiparasitic compounds has been the coordination of an organic ligand with known or potential biological activity, to a metal centre or an organometallic core. Classical metal coordination complexes or organometallic compounds could be designed as multifunctional agents joining, in a single molecule, different chemical species that could affect different parasitic targets. This review is focused on the rational design of palladium(II) and platinum(II) compounds with bioactive ligands as prospective drugs against trypanosomatid parasites that has been conducted by our group during the last 20 years.

scholarly journals The Role of Anisotropic Exchange in Single Molecule Magnets: A CASSCF/NEVPT2 Study of the Fe4 SMM Building Block [Fe2(OCH3)2(dbm)4] Dimer

2016 ◽  
Author(s):  
Alessandro Lunghi ◽  
Federico Totti
Keyword(s):  
Single Molecule ◽  
Building Block ◽  
Rational Design ◽  
Organic Ligand ◽  
Phenyl Group ◽  
Molecular Magnetism ◽  
Aliphatic Chain ◽  
Single Molecule Magnets ◽  
Anisotropic Exchange

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe2(OCH3)2(dbm)4]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe4RC(CH2O)3)2(dpm)6] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Synthesis and Biological Evaluation of Novel 4,5,6,7-Tetrahydrobenzo[D]-Thiazol-2- Yl Derivatives Derived from Dimedone with Anti-Tumor, C-Met, Tyrosine Kinase and Pim-1 Inhibitions

2019 ◽  
Vol 19 (12) ◽  
pp. 1438-1453 ◽  
Author(s):  
Rafat M. Mohareb ◽  
Amr S. Abouzied ◽  
Nermeen S. Abbas
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Cell ◽  
Cell Lines ◽  
Single Molecule ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
New Drugs ◽  
Tumor Cell Lines ◽  
Thiazole Derivatives ◽  
Wide Range

Background: Dimedone and thiazole moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. Thiazole derivatives are a very important class of compounds due to their wide range of pharmaceutical and therapeutic activities. On the other hand, dimedone is used to synthesize many therapeutically active compounds. Therefore, the combination of both moieties through a single molecule to produce heterocyclic compounds will produce excellent anticancer agents. Objective: The present work reports the synthesis of 47 new substances belonging to two classes of compounds: Dimedone and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. To achieve this goal, our strategy was to synthesize a series of 4,5,6,7-tetrahydrobenzo[d]-thiazol-2-yl derivatives using the reaction of the 2-bromodimedone with cyanothioacetamide. Methods: The reaction of 2-bromodimedone with cyanothioacetamide gave the 4,5,6,7-tetrahydrobenzo[d]- thiazol-2-yl derivative 4. The reactivity of compound 4 towards some chemical reagents was observed to produce different heterocyclic derivatives. Results: A cytotoxic screening was performed to evaluate the performance of the new derivatives in six tumor cell lines. Thirteen compounds were shown to be promising toward the tumor cell lines which were further evaluated toward five tyrosine kinases. Conclusion: The results of antitumor screening showed that many of the tested compounds were of high inhibition towards the tested cell lines. Compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 21b, 21c, 20d and 21d were the most potent compounds toward c-Met kinase and PC-3 cell line. The most promising compounds 6c, 8c, 11b, 11d, 13b, 14b, 15c, 15g, 20c, 20d, 21b, 21c and 21d were further investigated against tyrosine kinase (c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR). Compounds 6c, 11b, 11d, 14b, 15c, and 20d were selected to examine their Pim-1 kinase inhibition activity the results revealed that compounds 11b, 11d and 15c had high activities.

scholarly journals Rational design of protein-specific folding modifiers

2020 ◽  
Author(s):  
Anirban Das ◽  
Anju Yadav ◽  
Mona Gupta ◽  
R Purushotham ◽  
Vishram L. Terse ◽  
...  
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Force Measurements ◽  
Folding Nucleus ◽  
Dynamics Simulations ◽  
General Method

AbstractProtein folding can go wrong in vivo and in vitro, with significant consequences for the living cell and the pharmaceutical industry, respectively. Here we propose a general design principle for constructing small peptide-based protein-specific folding modifiers. We construct a ‘xenonucleus’, which is a pre-folded peptide that resembles the folding nucleus of a protein, and demonstrate its activity on the folding of ubiquitin. Using stopped-flow kinetics, NMR spectroscopy, Förster Resonance Energy transfer, single-molecule force measurements, and molecular dynamics simulations, we show that the ubiquitin xenonucleus can act as an effective decoy for the native folding nucleus. It can make the refolding faster by 33 ± 5% at 3 M GdnHCl. In principle, our approach provides a general method for constructing specific, genetically encodable, folding modifiers for any protein which has a well-defined contiguous folding nucleus.

TOPOLOGICAL INDICES – WHY AND HOW

2021 ◽  
Author(s):  
Ivan Gutman ◽  
Keyword(s):  
Single Molecule ◽  
Chemical Structure ◽  
Chemical Reactivity ◽  
Chemical Species ◽  
Chemical Compounds ◽  
Simple Calculation ◽  
Topological Indices ◽  
High Level ◽  
Complex Phenomena ◽  
Real World Problems

By means of presently available high-level computational methods, based on quantum theory, it is possible to determine (predict) the main structural, electronic, energetic, geometric, and thermodynamic properties of a particular chemical species (usually a molecule), as well as the ways in which it changes in chemical reactions. When one needs to estimate such properties of thousands or millions of chemical species, such high-level calculations are no more feasible. Then simpler, but less accurate, approaches are necessary. One such approach utilized so-called “topological indices”. According to IUPAC ‘s definition [Pure Appl. Chem. 69 (1997) 1137]: A topological index is a numerical value associated with chemical constitution for correlation of chemical structure with various physical properties, chemical reactivity or biological activity. In the first part of the lecture, we show that „numerical values“are associated with many other complex phenomena, encountered in various areas of human activity, implying that „topological indices“ are used far beyond chemistry. Next, we discuss the number of possible chemical compounds. Simple calculation shows that the number of possible compounds zillion times exceeds the number of those that have been experimentally characterized. Even worse, in the entire Universe, there is not enough matter to make at least a single molecule of each possible compound. In the second part of the lecture, a few most popular topological indices will be presented, as well as the way in which these can be (and are being) applied in treating real-world problems.

scholarly journals Rational design of DNA nanostructures for single molecule biosensing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mukhil Raveendran ◽  
Andrew J. Lee ◽  
Rajan Sharma ◽  
Christoph Wälti ◽  
Paolo Actis
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Dna Nanostructures

Lanthanide Doped Complexes and Organometallic Clusters: Design Strategies and their Applications in Biology and Photonics

2019 ◽  
Vol 9 (3) ◽  
pp. 166-217 ◽  
Author(s):  
Gangadharan A. Kumar
Keyword(s):  
Nanostructured Materials ◽  
Rational Design ◽  
Near Infrared ◽  
Organic Ligand ◽  
Central Core ◽  
Design Strategies ◽  
Ceramic Core ◽  
Light Emitting ◽  
Potential Applications ◽  
Lanthanide Atoms

In this review, we discuss the rational design of a new class of lanthanide-doped organometallic nanostructured materials called `molecular minerals`. Molecular minerals are nanostructured materials with a ceramic core made from chalcogenide groups and other heavy metals. Part of the central core atoms is replaced by suitable lanthanide atoms to impart fluorescent spectral properties. The ceramic core is surrounded by various types of organic networks thus making the structure partly ceramic and organic. The central core has superior optical properties and the surrounding organic ligand makes it easy to dissolve several kinds of organic solvents and fluoropolymers to make several kinds of active and passive photonic devices. This chapter starts with elaborate design strategies of lanthanidebased near-infrared emitting materials followed by the experimental results of selected near-infrared emitting lanthanide clusters. Finally, their potential applications in telecommunication, light-emitting diodes and medical imaging are discussed.

scholarly journals Towards rational design and optimization of near-field enhancement and spectral tunability of hybrid core-shell plasmonic nanoprobes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Debadrita Paria ◽  
Chi Zhang ◽  
Ishan Barman
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Near Infrared ◽  
Theoretical Calculations ◽  
Near Field ◽  
Field Enhancement ◽  
Infrared Region ◽  
Core Shell ◽  
Optimization Strategy ◽  
Design And Optimization

Abstract In biology, sensing is a major driver of discovery. A principal challenge is to create a palette of probes that offer near single-molecule sensitivity and simultaneously enable multiplexed sensing and imaging in the “tissue-transparent” near-infrared region. Surface-enhanced Raman scattering and metal-enhanced fluorescence have shown substantial promise in addressing this need. Here, we theorize a rational design and optimization strategy to generate nanostructured probes that combine distinct plasmonic materials sandwiching a dielectric layer in a multilayer core shell configuration. The lower energy resonance peak in this multi-resonant construct is found to be highly tunable from visible to the near-IR region. Such a configuration also allows substantially higher near-field enhancement, compared to a classical core-shell nanoparticle that possesses a single metallic shell, by exploiting the differential coupling between the two core-shell interfaces. Combining such structures in a dimer configuration, which remains largely unexplored at this time, offers significant opportunities not only for near-field enhancement but also for multiplexed sensing via the (otherwise unavailable) higher order resonance modes. Together, these theoretical calculations open the door for employing such hybrid multi-layered structures, which combine facile spectral tunability with ultrahigh sensitivity, for biomolecular sensing.

scholarly journals Correction: Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive β-roll peptide-based hydrogels

2020 ◽  
Vol 8 (20) ◽  
pp. 4527-4527
Author(s):  
Lichao Liu ◽  
Han Wang ◽  
Yueying Han ◽  
Shanshan Lv ◽  
Jianfeng Chen
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Force Spectroscopy ◽  
Single Molecule Force Spectroscopy

Correction for ‘Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive β-roll peptide-based hydrogels’ by Lichao Liu et al., J. Mater. Chem. B, 2018, 6, 5303–5312, DOI: 10.1039/C8TB01511B.

Simulations of Chemotaxis and Random Motility in Finite Domains

2004 ◽  
Vol 845 ◽  
Author(s):  
Ehsan Jabbarzadeh ◽  
Cameron F. Abrams
Keyword(s):  
Boundary Conditions ◽  
Cellular Response ◽  
Rational Design ◽  
Computational Simulation ◽  
Concentration Field ◽  
Chemical Species ◽  
Reaction Diffusion Equation ◽  
Cellular Transport ◽  
Pore Level ◽  
Reactive Surfaces

ABSTRACTRational design and selection of candidate porous biomaterials to serve as tissue engineering constructs rests on our ability to understand the influence of the porous microarchitecture on the transport of chemical species (e.g., nutrients and signaling compounds), fluid flow, and cellular locomotion and growth. We have begun to study the behavior of chemotactically mobile cells in response to unsteady signaling molecule concentration fields using a computational simulation-based model. The model couples fully time-dependent finite-difference solution of a reaction-diffusion equation for the concentration field of a generic chemoattractant to biased random walks representing individual moving cells. This model is a first step in building a quantitative, pore-level model of mass and cellular transport in porous tissue-engineered constructs. In these proceedings, we focus on our recent findings regarding the influence of flux-reactive boundary conditions in heterogeneous 2D domains on the chemotactic response of otherwise randomly moving cells. In particular, we find that, when cells are forced to “crawl” around obstacles in order to approach a point source of chemoattractant, the reactivity of the obstacle surface with respect to the chemoattractant strongly determines the morphology of the cells' paths of locomotion. Cells crawl along non-reactive surfaces and strongly avoid reactive surfaces, due to the nature of the chemoattractant concentration gradients near the surface. We show further that tuning the reactivity of the surfaces of two obstacles defining a gap can control the passage of cells through the gap. From our work, we infer the importance of a proper treatment of boundary conditions in any future pore-level quantitatve modeling of mass transport and cellular response in porous media.

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