Distributed polarizabilities derived from induction energies: A finite perturbation approach

2000 ◽  
Vol 112 (6) ◽  
pp. 2709-2717 ◽  
Author(s):  
Nihan Celebi ◽  
János G. Ángyán ◽  
François Dehez ◽  
Claude Millot ◽  
Christophe Chipot
Keyword(s):  
Perturbation Approach ◽  
Finite Perturbation

Zur Beschreibung weitreichender Kopplungen mittels der Pars-Orbital-Methode / Long-range Couplings, Methyl-substituted Coumarines and Carbostyriles, Pars-Orbital and Pertur-bational Calculations

1981 ◽  
Vol 36 (11) ◽  
pp. 1222-1224
Author(s):  
Walter Fabian ◽  
Heinz Sterk
Keyword(s):  
Long Range ◽  
Threshold Value ◽  
Perturbation Approach ◽  
Finite Perturbation

An attempt has been made to correlate long range couplings in a series of methyl-substituted coumarines and carbostyriles with the character orders of the corresponding propen- and methyl-butadienfragments. In the case that these character orders exceed a threshold value of about 0.700, relatively large long-range couplings are to be expected. In addition calculations of these couplings by the finite perturbation approach have been performed.

A Free Energy Perturbation Approach to Estimate the Intrinsic Solubilities of Drug-like Small Molecules

2019 ◽  
Author(s):  
Sayan Mondal ◽  
Gary Tresadern ◽  
Jeremy Greenwood ◽  
Byungchan Kim ◽  
Joe Kaus ◽  
...  
Keyword(s):  
Solid State ◽  
Small Molecules ◽  
Three Dimensional ◽  
Aqueous Solubility ◽  
Computational Approach ◽  
Free Energy Perturbation ◽  
Perturbation Approach ◽  
Energy Perturbation ◽  
State Form ◽  
Good Agreement

<p>Optimizing the solubility of small molecules is important in a wide variety of contexts, including in drug discovery where the optimization of aqueous solubility is often crucial to achieve oral bioavailability. In such a context, solubility optimization cannot be successfully pursued by indiscriminate increases in polarity, which would likely reduce permeability and potency. Moreover, increasing polarity may not even improve solubility itself in many cases, if it stabilizes the solid-state form. Here we present a novel physics-based approach to predict the solubility of small molecules, that takes into account three-dimensional solid-state characteristics in addition to polarity. The calculated solubilities are in good agreement with experimental solubilities taken both from the literature as well as from several active pharmaceutical discovery projects. This computational approach enables strategies to optimize solubility by disrupting the three-dimensional solid-state packing of novel chemical matter, illustrated here for an active medicinal chemistry campaign.</p>

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