Widespread misinterpretation of pKa terminology and its consequences DOI Creative Commons
Jonathan W. Zheng, Ivo Leito, William H. Green

et al.

Published: Aug. 8, 2024

The acid dissociation constant (pK a), which quantifies the propensity for a solute to donate proton its solvent, is crucial drug design and synthesis, environmental fate studies, chemical manufacturing, many other fields. Unfortunately, terminology used describing base phenomena inconsistent, causing large potential misinterpretation. In this work, we examine systematic confusion underlying definition of “acidic” “basic” pKa values zwitterionic compounds. Due confusion, some data misrepresented in repositories, including widely- highly trusted ChEMBL Database. Such datasets are widely supply training prediction models, hence, errors makes model performance worse. Herein, discuss intricacies issue. We make suggestions acid-base phenomena, stewarding datasets, given high potentially impact accurately phenomena.

Language: Английский

Predicting solvation free energies for neutral molecules in any solvent with openCOSMO-RS DOI Creative Commons
Simon Müller, Thomas Nevolianis, Miquel García‐Ratés

et al.

Fluid Phase Equilibria, Journal Year: 2024, Volume and Issue: unknown, P. 114250 - 114250

Published: Oct. 1, 2024

Language: Английский

Citations

6
pKa Prediction in Non-Aqueous Solvents DOI Creative Commons
Jonathan W. Zheng, Emad Al Ibrahim, William H. Green

et al.

Published: May 13, 2024

Acid dissociation constants (pKa) are widely measured and studied, most typically in water. Comparatively few datasets models for non-aqueous pKa values exist. In this work, we demonstrate how the one solvent can be accurately determined using reference data another solvent, corrected by solvation energy calculations from COSMO-RS method. We benchmark approach ten different solvents, find that calculated six solvents deviate experimental on average less than 1 pH unit. observe comparable performance a more diverse test set including amino acids drug molecules, with higher error large molecules. The model four other is worse, some MAEs exceeding 3 units; discuss such errors arise due to both inconsistency calibration. Finally, technique used estimate proton transfer between use report value of proton’s formamide, quantity has does not have consensus literature.

Language: Английский

Citations

1
Perspective on Automated Predictive Kinetics using Estimates derived from Large Datasets DOI Creative Commons
William H. Green

Published: May 28, 2024

A longstanding project of the chemical kinetics community is to predict reaction rates and behavior reacting systems, even for systems where there are no experimental data. Many important (atmosphere, combustion, pyrolysis, partial oxidations) involve a large number reactions occurring simultaneously, intermediates that have never been observed, making this goal more challenging. Improvements in our ability compute rate coefficients other parameters accurately from first principles, improvements automated kinetic modeling software, partially overcome many challenges. Indeed, some cases quite complicated models constructed which predicted results independent experiments. However, process constructing models, deciding measure or ab initio, relies on accurate estimates (and indeed most numerical estimates.) Machine-learned trained datasets can improve accuracy these estimates, allow better integration quantum chemistry The need continued development shared (perhaps open-source) software databases, directions improvement, highlighted. As we model weaknesses traditional ways doing modeling, testing exposed, identifying several challenges future research by

Language: Английский

Citations

1
Widespread Misinterpretation of pKa Terminology for Zwitterionic Compounds and Its Consequences DOI
Jonathan W. Zheng, Ivo Leito, William H. Green

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

The acid dissociation constant (pKa), which quantifies the propensity for a solute to donate proton its solvent, is crucial drug design and synthesis, environmental fate studies, chemical manufacturing, many other fields. Unfortunately, terminology used describing acid–base phenomena sometimes inconsistent, causing large potential misinterpretation. In this work, we examine systematic confusion underlying definition of "acidic" "basic" pKa values zwitterionic compounds. Due confusion, some data are misrepresented in repositories, including widely highly trusted ChEMBL database. Such datasets frequently supply training prediction models, hence, errors make model performance worse. Herein, discuss intricacies issue. We suggestions phenomena, stewarding datasets, given high potentially impact downstream applications.

Language: Английский

Citations

1
A Dual Experimental–Theoretical Perspective on ESPT Photoacids and Their Challenges Ahead DOI Creative Commons
Niklas Sülzner, Gregor Jung, Patrick Nuernberger

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

50 years after Th. Förster, 5 D. Huppert and M. Eigen: proton transfer as one of the best studied chemical reactions is still under debate paves way for new developments in physical theoretical chemistry.

Language: Английский

Citations

1
pKa prediction in non‐aqueous solvents DOI Creative Commons
Jonathan W. Zheng, Emad Al Ibrahim, Ivari Kaljurand

et al.

Journal of Computational Chemistry, Journal Year: 2024, Volume and Issue: 46(1)

Published: Dec. 11, 2024

Acid dissociation constants (

Language: Английский

Citations

1
pKa Prediction in Non-Aqueous Solvents DOI Creative Commons
Jonathan W. Zheng, Emad Al Ibrahim, William H. Green

et al.

Published: May 10, 2024

Acid dissociation constants (pKa) are widely measured and studied, most typically in water. Comparatively few datasets models for non-aqueous pKa values exist. In this work, we demonstrate how the one solvent can be accurately determined using reference data another solvent, corrected by solvation energy calculations from COSMO-RS method. We benchmark approach ten different solvents, find that calculated six solvents deviate experimental on average less than 1 pH unit. observe comparable performance a more diverse test set including amino acids drug molecules, with higher error large molecules. The model four other is worse, some MAEs exceeding 3 units; discuss such errors arise due to both inconsistency calibration. Finally, technique used estimate proton transfer between use report value of proton’s formamide, quantity has does not have consensus literature.

Language: Английский

Citations

0
Perspective on automated predictive kinetics using estimates derived from large datasets DOI Creative Commons
William H. Green

International Journal of Chemical Kinetics, Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract A longstanding project of the chemical kinetics community is to predict reaction rates and behavior reacting systems, even for systems where there are no experimental data. Many important (atmosphere, combustion, pyrolysis, partial oxidations) involve a large number reactions occurring simultaneously, intermediates that have never been observed, making this goal more challenging. Improvements in our ability compute rate coefficients other parameters accurately from first principles, improvements automated kinetic modeling software, partially overcome many challenges. Indeed, some cases quite complicated models constructed which predicted results independent experiments. However, process constructing models, deciding measure or ab initio, relies on accurate estimates (and indeed most numerical estimates.) Machine‐learned trained datasets can improve accuracy these estimates, allow better integration quantum chemistry The need continued development shared (perhaps open‐source) software databases, directions improvement, highlighted. As we model weaknesses traditional ways doing modeling, testing exposed, identifying several challenges future research by community.

Language: Английский

Citations

0
Widespread misinterpretation of pKa terminology and its consequences DOI Creative Commons
Jonathan W. Zheng, Ivo Leito, William H. Green

et al.

Published: Aug. 7, 2024

The acid dissociation constant (pK a), which quantifies the propensity for a solute to donate proton its solvent, is crucial drug design and synthesis, environmental fate studies, chemical manufacturing, many other fields. Unfortunately, terminology used describing base phenomena inconsistent, causing large potential misinterpretation. In this work, we examine systematic confusion underlying definition of “acidic” “basic” pKa values zwitterionic compounds. Due confusion, some data misrepresented in repositories, including widely- highly trusted ChEMBL Database. Such datasets are widely supply training prediction models, hence, errors makes model performance worse. Herein, discuss intricacies issue. We make suggestions acid-base phenomena, stewarding datasets, given high potentially impact accurately phenomena.

Language: Английский

Citations

0
Widespread misinterpretation of pKa terminology and its consequences DOI Creative Commons
Jonathan W. Zheng, Ivo Leito, William H. Green

et al.

Published: Aug. 8, 2024

The acid dissociation constant (pK a), which quantifies the propensity for a solute to donate proton its solvent, is crucial drug design and synthesis, environmental fate studies, chemical manufacturing, many other fields. Unfortunately, terminology used describing base phenomena inconsistent, causing large potential misinterpretation. In this work, we examine systematic confusion underlying definition of “acidic” “basic” pKa values zwitterionic compounds. Due confusion, some data misrepresented in repositories, including widely- highly trusted ChEMBL Database. Such datasets are widely supply training prediction models, hence, errors makes model performance worse. Herein, discuss intricacies issue. We make suggestions acid-base phenomena, stewarding datasets, given high potentially impact accurately phenomena.

Language: Английский

Citations

0