scholarly journals Thermal sigmatropic [1,j] shifts in cyclic systems. A perturbation approach and INDO calculations

1977 ◽  
Vol 99 (2) ◽  
pp. 392-397 ◽  
Author(s):  
Jan R. De Dobbelaere ◽  
Jan M. F. Van Dijk ◽  
Jan W. De Haan ◽  
Henk M. Buck
Keyword(s):  
Perturbation Approach ◽  
Indo Calculations ◽  
Cyclic Systems

ChemInform Abstract: THERMAL SIGMATROPIC (1,J) SHIFTS IN CYCLIC SYSTEMS. A PERTURBATION APPROACH AND INDO CALCULATIONS

1977 ◽  
Vol 8 (15) ◽  
pp. no-no
Author(s):  
J. R. DE DOBBELAERE ◽  
J. M. F. VAN DIJK ◽  
J. W. DE HAAN ◽  
H. M. BUCK
Keyword(s):  
Perturbation Approach ◽  
Indo Calculations ◽  
Cyclic Systems

FREE AND FORCED RESPONSE OF MISTUNED LINEAR CYCLIC SYSTEMS: A SINGULAR PERTURBATION APPROACH

1998 ◽  
Vol 211 (5) ◽  
pp. 761-789 ◽  
Author(s):  
G.S. Happawana ◽  
O.D.I. Nwokah ◽  
A.K. Bajaj ◽  
M. Azene
Keyword(s):  
Singular Perturbation ◽  
Forced Response ◽  
Perturbation Approach ◽  
Cyclic Systems

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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