scholarly journals The AIBLHiCoS Method: Predicting Aqueous pKa Values from Gas-Phase Equilibrium Bond Lengths

2016 ◽  
Vol 56 (3) ◽  
pp. 471-483 ◽  
Author(s):  
Cate Anstöter ◽  
Beth A. Caine ◽  
Paul L. A. Popelier
Keyword(s):  
Phase Equilibrium ◽  
Gas Phase ◽  
Pka Values ◽  
Bond Lengths ◽  
Aqueous Pka

scholarly journals Experiment stands corrected: accurate prediction of the aqueous pKa values of sulfonamide drugs using equilibrium bond lengths

2019 ◽  
Vol 10 (25) ◽  
pp. 6368-6381 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul L. A. Popelier
Keyword(s):  
Accurate Prediction ◽  
Strongly Correlated ◽  
Pka Values ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values.

Experiment Stands Corrected: Accurate Prediction of the Aqueous pKa Values of Sulfonamide Drugs Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul Popelier
Keyword(s):  
Strongly Correlated ◽  
Pka Values ◽  
Pka Prediction ◽  
Thermodynamic Cycles ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
Experimental Values ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values. Models are constructed for three variants of the SO2NHR group: primary benzene sulfonamide derivatives (e.g. diuretic drugs furosemide and hydrochlorothiazide), N-phenyl substituted 4-amino-N-phenylbenzenesulfonamide analogues (e.g. the sulfa antibiotic sulfadiazine) and phenylsulfonylureas (e.g. insulin secretogogue, glimepiride). In the context of these compounds, we present solutions to some of the more complex challenges in pKa prediction: (i) prediction for multiprotic compounds, (ii) predicting macroscopic values for compounds that tautomerize, and (iii) quantum chemical pKa prediction for compounds with more than 50 atoms. Using bond lengths as a powerful descriptor of ionization feasibility, we also identify that literature values for drug compounds celecoxib, glimepiride and glipizide are inaccurate. Our newly measured experimental values match our initial predictions to within 0.26 pKa units, whereas previous values were found to deviate by up to 1.68 pKa units. For glimepiride, our corrected value denotes a percentage of ionization at intracellular pH, which is only now in excellent agreement with its known therapeutic efficacy. We propose that linear relationships between bond lengths and pKa should emerge for any set of congeners, thus providing a powerful method of pKa prediction obviating the need for thermodynamic cycles.

Experiment Stands Corrected: Accurate Prediction of the Aqueous pKa Values of Sulfonamide Drugs Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Paul Popelier
Keyword(s):  
Strongly Correlated ◽  
Pka Values ◽  
Pka Prediction ◽  
Thermodynamic Cycles ◽  
Bond Lengths ◽  
Linear Relationships ◽  
Aqueous Pka ◽  
Experimental Values ◽  
First Time ◽  
Sulfonamide Group

We show here for the first time that strongly correlated linear relationships exist between equilibrium bond lengths of the sulfonamide group and aqueous pKa values. Models are constructed for three variants of the SO2NHR group: primary benzene sulfonamide derivatives (e.g. diuretic drugs furosemide and hydrochlorothiazide), N-phenyl substituted 4-amino-N-phenylbenzenesulfonamide analogues (e.g. the sulfa antibiotic sulfadiazine) and phenylsulfonylureas (e.g. insulin secretogogue, glimepiride). In the context of these compounds, we present solutions to some of the more complex challenges in pKa prediction: (i) prediction for multiprotic compounds, (ii) predicting macroscopic values for compounds that tautomerize, and (iii) quantum chemical pKa prediction for compounds with more than 50 atoms. Using bond lengths as a powerful descriptor of ionization feasibility, we also identify that literature values for drug compounds celecoxib, glimepiride and glipizide are inaccurate. Our newly measured experimental values match our initial predictions to within 0.26 pKa units, whereas previous values were found to deviate by up to 1.68 pKa units. For glimepiride, our corrected value denotes a percentage of ionization at intracellular pH, which is only now in excellent agreement with its known therapeutic efficacy. We propose that linear relationships between bond lengths and pKa should emerge for any set of congeners, thus providing a powerful method of pKa prediction obviating the need for thermodynamic cycles.

scholarly journals Prediction of Aqueous pKaValues for Guanidine-Containing Compounds Using Ab Initio Gas-Phase Equilibrium Bond Lengths

ACS Omega ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 3835-3850 ◽  
Author(s):  
Beth A. Caine ◽  
Christophe Dardonville ◽  
Paul L. A. Popelier
Keyword(s):  
Phase Equilibrium ◽  
Ab Initio ◽  
Gas Phase ◽  
Bond Lengths

Prediction of Alkanolamine pKa Values by Combined Molecular Dynamics Free Energy Simulations and ab initio Calculations

2019 ◽  
Author(s):  
Javad Noroozi ◽  
William Smith
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Ab Initio Calculations ◽  
Gas Phase ◽  
Quantum Chemical ◽  
Phase Reaction ◽  
Pka Values ◽  
Gas Phase Reaction ◽  
Reaction Free Energy ◽  
Energy Simulations

We use molecular dynamics free energy simulations in conjunction with quantum chemical calculations of gas phase reaction free energy to predict alkanolamines pka values. <br>

Molecular orbital structures of sulfones

1982 ◽  
Vol 60 (6) ◽  
pp. 730-734 ◽  
Author(s):  
Russell J. Boyd ◽  
Jeffrey P. Szabo
Keyword(s):  
Crystal Structure ◽  
Gas Phase ◽  
Molecular Orbital ◽  
Geometry Optimization ◽  
Membered Ring ◽  
Molecular Orbital Calculations ◽  
Bond Lengths ◽  
Comparison With Experiment ◽  
The Difference

Abinitio molecular orbital calculations are reported for several cyclic and acyclic sulfones. The geometries of XSO2Y, where X, Y = H, F, or CH3 are optimized at the STO-3G* level. Similar calculations are reported for the smallest cyclic sulfone, thiirane-1,1 -dioxide, as well as the corresponding sulfoxide, thiirane-1-oxide, and the parent sulfide, thiirane. Where comparison with experiment is possible, the agreement is satisfactory. In order to consider the possibility of substantial differences between axial and equatorial S—O bonds in the gas phase, as observed in the crystal structure of 5H,8H-dibenzo[d,f][1,2]-dithiocin-1,1-dioxide, STO-3G* calculations are reported for a six-membered ring, thiane-1,1-dioxide, and a model eight-membered ring. Limited geometry optimization of the axial and equatorial S—O bonds in the chair conformations of the six- and eight-membered rings leads to bond lengths of 1.46 Å with the difference being less than 0.01 Å.

Improved synthesis and crystal structure of the parent 1,3,5-trisilacyclohexane

2016 ◽  
Vol 71 (1) ◽  
pp. 77-79 ◽  
Author(s):  
Eugen Weisheim ◽  
Hans-Georg Stammler ◽  
Norbert W. Mitzel
Keyword(s):  
Crystal Structure ◽  
Solid State ◽  
Electron Diffraction ◽  
Gas Phase ◽  
Gaseous Phase ◽  
Chair Conformation ◽  
Gas Electron Diffraction ◽  
State Structure ◽  
Synthesis And Crystal Structure ◽  
Bond Lengths

AbstractThe crystal structure and an improved synthesis of 1,3,5-trisilacyclohexane are reported. The solid state structure is compared with the reported structure determined in the gas phase by gas electron diffraction (GED). 1,3,5-Trisilacyclohexane adopts a chair conformation in the solid state. The Si–C bond lengths as well as all angles of 1,3,5-trisilacyclohexane in the solid state have similar dimensions compared to the structure in the gaseous phase.

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