scholarly journals Aqueous pKa prediction for tautomerizable compounds using equilibrium bond lengths

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Torquil Fraser ◽  
Nathan Kidley ◽  
Christophe Dardonville ◽  
...  
Keyword(s):  
Pka Prediction ◽  
Bond Lengths ◽  
Aqueous Pka

scholarly journals Solving the Problem of Aqueous pKa Prediction for Tautomerizable Compounds Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Torquil Fraser ◽  
Nathan Kidley ◽  
Christophe Dardonville ◽  
...  
Keyword(s):  
Ab Initio ◽  
Pka Prediction ◽  
Bond Lengths ◽  
Aqueous Pka

Our new pKa predictor called AIBL outperforms Marvin for the well-known challenge of tautomerizable compounds. The powerful descriptors used here are simply ab initio equilibrium bond lengths. We also correct the literature experimental value for the herbicide Profoxydim, from a previous value 5.91 to a new value of 4.82. This is a fine and rare example of theory correcting experiment.

scholarly journals Solving the Problem of Aqueous pKa Prediction for Tautomerizable Compounds Using Equilibrium Bond Lengths

2019 ◽  
Author(s):  
Beth A. Caine ◽  
Maddalena Bronzato ◽  
Torquil Fraser ◽  
Nathan Kidley ◽  
Christophe Dardonville ◽  
...  
Keyword(s):  
Ab Initio ◽  
Pka Prediction ◽  
Bond Lengths ◽  
Aqueous Pka

Our new pKa predictor called AIBL outperforms Marvin for the well-known challenge of tautomerizable compounds. The powerful descriptors used here are simply ab initio equilibrium bond lengths. We also correct the literature experimental value for the herbicide Profoxydim, from a previous value 5.91 to a new value of 4.82. This is a fine and rare example of theory correcting experiment.

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 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.

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

Vibrational spectra of aquadioxotetra; peroxodivanadates(V) M2[V2O2(O2)4(H2O)]·xH2O (M = N(CH3)4, Cs)

1990 ◽  
Vol 55 (6) ◽  
pp. 1485-1490 ◽  
Author(s):  
Peter Schwendt ◽  
Milan Sýkora
Keyword(s):  
Raman Spectra ◽  
Vibrational Spectra ◽  
Normal Coordinate Analysis ◽  
Force Constants ◽  
Infrared And Raman Spectra ◽  
Empirical Correlations ◽  
Normal Coordinate ◽  
Bond Lengths ◽  
Stretching Vibrations

The infrared and Raman spectra of M2[V2O2(O2)4(H2O)]·xH2O and M2[V2O2(O2)4(D2O)]·xD2O (M = N(CH3)4, Cs) were measured. In the region of the vanadium-oxygen stretching vibrations, the spectra were interpreted based on normal coordinate analysis, employing empirical correlations between the bond lengths and force constants.

scholarly journals Crystal structure of K[Hg(SCN)3] – a redetermination

2014 ◽  
Vol 70 (9) ◽  
pp. i46-i46 ◽  
Author(s):  
Matthias Weil ◽  
Thomas Häusler
Keyword(s):  
Crystal Structure ◽  
Room Temperature ◽  
Three Dimensional ◽  
Lattice Parameters ◽  
Bond Lengths ◽  
Dimensional Network ◽  
Anisotropic Displacement Parameters ◽  
Precision And Accuracy ◽  
Standard Deviations ◽  
Atomic Coordinates

The crystal structure of the room-temperature modification of K[Hg(SCN)3], potassium trithiocyanatomercurate(II), was redetermined based on modern CCD data. In comparison with the previous report [Zhdanov & Sanadze (1952).Zh. Fiz. Khim.26, 469–478], reliability factors, standard deviations of lattice parameters and atomic coordinates, as well as anisotropic displacement parameters, were revealed for all atoms. The higher precision and accuracy of the model is, for example, reflected by the Hg—S bond lengths of 2.3954 (11), 2.4481 (8) and 2.7653 (6) Å in comparison with values of 2.24, 2.43 and 2.77 Å. All atoms in the crystal structure are located on mirror planes. The Hg2+cation is surrounded by four S atoms in a seesaw shape [S—Hg—S angles range from 94.65 (2) to 154.06 (3)°]. The HgS4polyhedra share a common S atom, building up chains extending parallel to [010]. All S atoms of the resulting1∞[HgS2/1S2/2] chains are also part of SCN−anions that link these chains with the K+cations into a three-dimensional network. The K—N bond lengths of the distorted KN7polyhedra lie between 2.926 (2) and 3.051 (3) Å.

scholarly journals Influence of Copper(I) Halides on the Reactivity of Aliphatic Carbodiimides

2020 ◽  
Vol 3 (1) ◽  
pp. 20
Author(s):  
Valentina Ferraro ◽  
Marco Bortoluzzi
Keyword(s):  
Density Functional Theory ◽  
Electronic Structure ◽  
General Formula ◽  
Electron Density ◽  
Density Functional ◽  
Functional Theory ◽  
Fukui Functions ◽  
Bond Lengths ◽  
Linear Complexes ◽  
Nitrogen Bond

The influence of copper(I) halides CuX (X = Cl, Br, I) on the electronic structure of N,N′-diisopropylcarbodiimide (DICDI) and N,N′-dicyclohexylcarbodiimide (DCC) was investigated by means of computational DFT (density functional theory) methods. The coordination of the considered carbodiimides occurs by one of the nitrogen atoms, with the formation of linear complexes having a general formula of [CuX(carbodiimide)]. Besides varying the carbon–nitrogen bond lengths, the thermodynamically favourable interaction with Cu(I) reduces the electron density on the carbodiimides and alters the energies of the (NCN)-centred, unoccupied orbitals. A small dependence of these effects on the choice of the halide was observable. The computed Fukui functions suggested negligible interaction of Cu(I) with incoming nucleophiles, and the reactivity of carbodiimides was altered by coordination mainly because of the increased electrophilicity of the {NCN} fragments.

Sign in / Sign up

Export Citation Format

Share Document