scholarly journals Quantum Mechanics Enables "Freedom of Design" in Molecular Property Space

2021 ◽  
Author(s):  
Leonardo Medrano Sandonas ◽  
Johannes Hoja ◽  
Brian G. Ernst ◽  
Alvaro Vazquez-Mayagoitia ◽  
Robert A. DiStasio Jr. ◽  
...  
Keyword(s):  
Single Molecule ◽  
Rational Design ◽  
Pareto Front ◽  
Molecular Property ◽  
Structure Property ◽  
Battery Materials ◽  
Property Data ◽  
Property Space ◽  
Equilibrium Structures ◽  
Compositional Changes

Rational design of molecules with targeted properties requires understanding quantum-mechanical (QM) structure-property/property-property relationships (SPR/PPR) across chemical compound space. We analyze these relationships using the QM7-X dataset---which includes multiple QM properties for ~4.2 M equilibrium and non-equilibrium structures of small (primarily organic) molecules. Instead of providing simple SPR/PPR that strictly follow physicochemical intuition, our analysis uncovers substantial flexibility in molecular property space (MPS) when searching for a single molecule with a desired pair of QM properties or distinct molecules with a targeted set of QM properties. As proof-of-concept, we used Pareto multi-property optimization to search for the most promising (i.e., highly polarizable and electrically stable) molecules for polymeric battery materials; without prior knowledge of this complex manifold of MPS, Pareto front analysis reflected this intrinsic flexibility and identified small directed structural/compositional changes that simultaneously optimize these properties. Our analysis of such extensive QM property data provides compelling evidence for an intrinsic “freedom of design” in MPS, and indicates that rational design of molecules with a diverse array of targeted QM properties is quite feasible.

scholarly journals Hydroxycinnamic Acid Antioxidants: An Electrochemical Overview

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
José Teixeira ◽  
Alexandra Gaspar ◽  
E. Manuela Garrido ◽  
Jorge Garrido ◽  
Fernanda Borges
Keyword(s):  
Rational Design ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Phenoxyl Radical ◽  
Free Radical Scavenger ◽  
Hydroxycinnamic Acid ◽  
Hydroxycinnamic Acids ◽  
Radical Scavenger ◽  
Redox Potentials ◽  
Structure Property

Hydroxycinnamic acids (such as ferulic, caffeic, sinapic, andp-coumaric acids) are a group of compounds highly abundant in food that may account for about one-third of the phenolic compounds in our diet. Hydroxycinnamic acids have gained an increasing interest in health because they are known to be potent antioxidants. These compounds have been described as chain-breaking antioxidants acting through radical scavenging activity, that is related to their hydrogen or electron donating capacity and to the ability to delocalize/stabilize the resulting phenoxyl radical within their structure. The free radical scavenger ability of antioxidants can be predicted from standard one-electron potentials. Thus, voltammetric methods have often been applied to characterize a diversity of natural and synthetic antioxidants essentially to get an insight into their mechanism and also as an important tool for the rational design of new and potent antioxidants. The structure-property-activity relationships (SPARs) correlations already established for this type of compounds suggest that redox potentials could be considered a good measure of antioxidant activity and an accurate guideline on the drug discovery and development process. Due to its magnitude in the antioxidant field, the electrochemistry of hydroxycinnamic acid-based antioxidants is reviewed highlighting the structure-property-activity relationships (SPARs) obtained so far.

Structural modification strategies for the rational design of red/NIR region BODIPYs

2014 ◽  
Vol 43 (13) ◽  
pp. 4778-4823 ◽  
Author(s):  
Hua Lu ◽  
John Mack ◽  
Yongchao Yang ◽  
Zhen Shen
Keyword(s):  
Rational Design ◽  
Structural Modification ◽  
Photophysical Properties ◽  
Structure Property ◽  
Structure Property Relationships

The structure–property relationships of red/NIR region BODIPY dyes is analyzed, so that trends in their photophysical properties can be readily compared.

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.

scholarly journals A Comprehensive Discovery Platform for Organophosphorus Ligands for Catalysis

2021 ◽  
Author(s):  
Tobias Gensch ◽  
Gabriel dos Passos Gomes ◽  
Pascal Friederich ◽  
Ellyn Peters ◽  
Theophile Gaudin ◽  
...  
Keyword(s):  
Structure Property ◽  
Vast Number ◽  
Structure Property Relationships ◽  
Reaction Optimization ◽  
Physicochemical Descriptors ◽  
Mechanical Methods ◽  
Quantitative Structure Property Relationships ◽  
Property Space ◽  
Novel Catalyst ◽  
Molecular Catalysts

The design of molecular catalysts typically involves reconciling multiple conflicting property requirements, largely relying on human intuition and local structural searches. However, the vast number of potential catalysts requires pruning of the candidate space by efficient property prediction with quantitative structure-property relationships. Data-driven workflows embedded in a library of potential catalysts can be used to build predictive models for catalyst performance and serve as a blueprint for novel catalyst designs. Herein we introduce <i>kraken</i>, a discovery platform covering monodentate organophosphorus(III) ligands providing comprehensive physicochemical descriptors based on representative conformer ensembles. Using quantum-mechanical methods, we calculated descriptors for 1,558 ligands, including commercially available examples, and trained machine learning models to predict properties of over 300,000 new ligands. We demonstrate the application of <i>kraken</i> to systematically explore the property space of organophosphorus ligands and how existing datasets in catalysis can be used to accelerate ligand selection during reaction optimization.

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

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.

scholarly journals A general approach for retrosynthetic molecular core analysis

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Jesús Naveja ◽  
B. Angélica Pilón-Jiménez ◽  
Jürgen Bajorath ◽  
José L. Medina-Franco
Keyword(s):  
Single Molecule ◽  
Chemical Space ◽  
Significant Proportion ◽  
Bipartite Network ◽  
Data Sets ◽  
Structure Property ◽  
Data Set ◽  
Chemical Structures ◽  
Structure Property Relationships ◽  
Analog Series

Abstract Scaffold analysis of compound data sets has reemerged as a chemically interpretable alternative to machine learning for chemical space and structure–activity relationships analysis. In this context, analog series-based scaffolds (ASBS) are synthetically relevant core structures that represent individual series of analogs. As an extension to ASBS, we herein introduce the development of a general conceptual framework that considers all putative cores of molecules in a compound data set, thus softening the often applied “single molecule–single scaffold” correspondence. A putative core is here defined as any substructure of a molecule complying with two basic rules: (a) the size of the core is a significant proportion of the whole molecule size and (b) the substructure can be reached from the original molecule through a succession of retrosynthesis rules. Thereafter, a bipartite network consisting of molecules and cores can be constructed for a database of chemical structures. Compounds linked to the same cores are considered analogs. We present case studies illustrating the potential of the general framework. The applications range from inter- and intra-core diversity analysis of compound data sets, structure–property relationships, and identification of analog series and ASBS. The molecule–core network herein presented is a general methodology with multiple applications in scaffold analysis. New statistical methods are envisioned that will be able to draw quantitative conclusions from these data. The code to use the method presented in this work is freely available as an additional file. Follow-up applications include analog searching and core structure–property relationships analyses.

Atomically dispersed M–N–C catalysts for the oxygen reduction reaction

2020 ◽  
Vol 8 (44) ◽  
pp. 23187-23201 ◽  
Author(s):  
Hao Xu ◽  
Dan Wang ◽  
Peixia Yang ◽  
Anmin Liu ◽  
Ruopeng Li ◽  
...  
Keyword(s):  
Oxygen Reduction Reaction ◽  
Oxygen Reduction ◽  
Rational Design ◽  
Reduction Reaction ◽  
Structure Property

The systematic summarization of synthesis–structure–property–mechanism correlations provides guidance for the rational design of an atomically dispersed M–N–C catalyst for the ORR.

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