1 Introduction 1.1 'Not too little - not too much', 1.2 Why a Database of Aqueous Intrinsic Solubility? 1.3 Database 1.4 Measurements Can Be Improved 1.5 Solubility- pH Profiles, Intrinsic Solubility, and Profile Distortions 2 Physicochemical Properties of Wiki-pS0 Database Molecules 2.1 Most Molecules in Database are Drug-Like or Drug-Relevant 2.2 Distribution of Intrinsic Solubility 2.
3 Interlaboratory Variance 2.4 Quality and Chemical Space of Experimental Data 2.5PROTACs: Lipinski's 'Rule Of 5' Characteristics 2.6Newly-Approved Drugs: Lipinski's 'Rule Of 5' Characteristics 2.7 Kier Flexibility Index, Φ , and Abraham H-Bond Acceptor Potential, B 2.8 Principal Component Analysis 2.9 Quantitative Estimate of Drug-Likeness 3 Solubility Prediction Methods 3.1 Overview of Solubility Prediction Models 3.
2 Gap between Prediction and Measurement 3.3 Yalkowsky General Solubility Equation (GSE) 3.4 'Flexible-Acceptor' General Solubility Equation, GSE( Φ,B ) 3.5 Abraham Solvation Equation (ABSOLV) 3.6 Breiman Random Forest Regression 4 Predicting of Solubility of PROTACs 4.1 Determination of the Three GSE( Φ,B ) Coefficients from Training Set Iso-( Φ+B ) Bins 4.2 'Flexible-Acceptor' Lipophilicity 4.3 ABSOLV Trained to Predict the Intrinsic Solubility of PROTACs 4.
4 RFR Training 4.5 Training Set Performances 4.6 Effect of Small Amounts of DMSO ('¤ 5 vol%) 4.7 Predicting Solubility of PROTACs 5 Predicting of Solubility of New Drugs 5.1 Trends in Physicochemical Properties of Emerging Drugs 5.2 Characteristics of Emerging Drugs (2016-2022) 5.3 Re-training of the Training Sets 5.4 Predicting Solubility of Newly-Approved Drugs 5.
5 Striving for Similarity Between Training Set and Test Set 6 Instruments with 'Intelligence' 6.1 Bjerrum Difference Plots for Saturated Solutions - Normalized Titration Curves 6.2 'Intelligent' Assay: Noyes-Whitney 'Dissolution Titration Template' (DTT) Method 6.3 High-Throughput Solubility Instrument with DMSO Bias Correction 6.4 Where to Aim Next Appendix - Data Sources, Solubility Definitions, Unit Conversions A1 Data Sources in Wiki-pS0 Database A1.1 'Kinetic Solubility' Measurements A1.2 Data for FDA Newly-Approved Drugs (2016-2022) A1.3 Data from Secondary Sources A.
1.4 Single-Source Measurements A1.5 Data from Miscellaneous Primary Sources A1.6 Sources of pKa Data A2 Definitions, Supersaturation, Cosolvents A2.1 Consensus Recommendations A2.2 pH Measurement A3 Solubility Units - Conversions to Molarity A4 Different Types of Aqueous Solubility of Ionizable Molecules A4.1 Single-Point Water Solubility of Free Acid/Base ( Sα / S βfor Free Acid/Base, or Simply Sw ) A4.2 Single-Point Solubility at a Particular Buffered pH ( SpH ) A4.
3 Single-Point Intrinsic Solubility ( S0 ) A4.4 Single-Point Water Solubility of Non-Disproportionating μ-Type Salt ( Ssalt or Sμ ) A4.5 Single-Point Water Solubility of Disproportionating δ-Type Salt ( Sδ ) General References Tabulation Organization and Notes TABULATION 1 - Wiki-pS0 TABULATION 2 - DMSO Bias-Corrected Solubility Tabulation References Index of Topics Index of Molecule Names Index of Registry Numbers (RN).