scholarly journals How metallylenes activate small molecules

2021 ◽  
Vol 12 (12) ◽  
pp. 4526-4535
Author(s):  
Pascal Vermeeren ◽  
Michael T. Doppert ◽  
F. Matthias Bickelhaupt ◽  
Trevor A. Hamlin
Keyword(s):  
Small Molecules ◽  
Quantum Chemical ◽  
Rational Design ◽  
Chemical Analyses

Quantum chemical analyses reveal how model metallylene catalysts activate H2. This is the first step towards the rational design of metallylenes for the activation of small molecules and subsequent reactions.

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

In the Quest for a Stable Triplet State in Small Polyaromatic Hydrocarbons : An In-Silico Tool for Rational Design and Prediction

2019 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Qualitative Agreement ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Spin Hamiltonian ◽  
Spin Frustration ◽  
Computationally Efficient ◽  
High Level

<div>Combining the roles of spin frustration and geometry of odd and even numbered rings in polyaromatic hydrocarbons (PAHs), we design small molecules that show exceedingly small singlet-triplet gaps and stable triplet ground states. Furthermore, a computationally efficient protocol with a model spin Hamiltonian is shown to be capable of qualitative agreement with respect to high level multireference calculations and therefore, can be used for fast molecular discovery and screening.</div>

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

scholarly journals A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

2016 ◽  
Vol 12 ◽  
pp. 125-138 ◽  
Author(s):  
Steven C Zimmerman
Keyword(s):  
Small Molecules ◽  
Supramolecular Chemistry ◽  
Myotonic Dystrophy ◽  
Small Molecule ◽  
Early Life ◽  
Rational Design ◽  
Early Experience ◽  
Therapeutic Agents ◽  
Early Career ◽  
Molecular Tweezers

This review summarizes part of the author’s research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host–guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples.

Rational Design of Small Molecules for a Novel Class of Anti-Cancer Drugs using a Phenylalanine Library

2006 ◽  
pp. 459-460
Author(s):  
Lajos Gera ◽  
Daniel C. Chan ◽  
Laimute Taraseviciene-Stewart ◽  
Vitalija Simkeviciene ◽  
Paul A. Bunn ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rational Design ◽  
Cancer Drugs ◽  
Anti Cancer

Rational Design of Cation Hosts – Prediction of Cation Selectivity by Quantum Chemical Calculations

2006 ◽  
Vol 220 (4_2006) ◽  
pp. 511-523 ◽  
Author(s):  
Michael Galle ◽  
Ralph Puchta ◽  
Nico J. R. van Eikema Hommes ◽  
Rudi van Eldik
Keyword(s):  
Quantum Chemical Calculations ◽  
Quantum Chemical ◽  
Rational Design ◽  
Cation Selectivity

Rational Design of Small Molecules to Implement Organic Quaternary Memory Devices

2015 ◽  
Vol 26 (1) ◽  
pp. 146-154 ◽  
Author(s):  
Qijian Zhang ◽  
Jinghui He ◽  
Hao Zhuang ◽  
Hua Li ◽  
Najun Li ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rational Design ◽  
Memory Devices

scholarly journals In the quest for a stable triplet state in small polyaromatic hydrocarbons: an in silico tool for rational design and prediction

2019 ◽  
Vol 10 (40) ◽  
pp. 9270-9276 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K. Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Ground States ◽  
Spin Frustration

Spin frustration plays a major role in reduction of singlet-triplet gaps and that is leveraged to design small molecules with stable triplet ground states.

scholarly journals Rational design of nanosystems for simultaneous drug delivery and photodynamic therapy by quantum mechanical modeling

Nanoscale ◽  
2019 ◽  
Vol 11 (33) ◽  
pp. 15576-15588 ◽  
Author(s):  
Moloud Kaviani ◽  
Cristiana Di Valentin
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Quantum Chemical ◽  
Rational Design ◽  
Quantum Chemical Study ◽  
Chemical Study ◽  
Quantum Mechanical ◽  
Mechanical Modeling

Multiscale quantum chemical study of dopamine-functionalized TiO2 nanoparticles loaded by doxorubicin with applications in drug delivery and photodynamic therapy.

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