Unified Physical Property Estimation Relationships, UPPER Item Type text; Electronic Dissertation Authors Lian, Bo Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 29/09/2021 05:50:41 Link to Item http://hdl.handle.net/10150/311104 1 UNIFIED PHYSICAL PROPERTY ESTIMATION RELATIONSHIPS, UPPER by Bo Lian ____________________________ A Dissertation Submitted to the Faculty of the DEPARTMENT OF PHARMACEUTICAL SCIENCES In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2013 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Bo Lian, titled Unified Physical Property Estimation Relationships, UPPER and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy. _______________________________________________________________________ Date: (05/16/2013) Samuel H Yalkowsky _______________________________________________________________________ Date: (05/16/2013) Michael Mayersohn _______________________________________________________________________ Date: (05/16/2013) Paul B Myrdal _______________________________________________________________________ Date: (05/16/2013) Edward D French _______________________________________________________________________ Date: (05/16/2013) Theodore J Price Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. ________________________________________________ Date: (05/16/2013) Dissertation Director: Samuel H Yalkowsky 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of the requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that an accurate acknowledgement of the source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Bo Lian 4 Table of Contents LIST OF TABLES .............................................................................................................. 6 LIST OF FIGURES ............................................................................................................ 7 ABSTRACT ........................................................................................................................ 8 1. Introduction ................................................................................................................. 9 2. Theoretical Background ............................................................................................ 11 2.1 The UPPER Scheme ............................................................................................. 11 2.2 Enthalpic Descriptors ............................................................................................ 14 2.3 Entropic Descriptors ............................................................................................. 15 2.3.1 Molecular Symmetry (σ) ................................................................................... 16 2.3.2 Molecular Flexibility (φ) ................................................................................... 16 2.3.3 Molecular Eccentricity (ε) ................................................................................ 17 2.3.4 Intercorrelation of Entropic Descriptors ........................................................... 18 3. DATA AND METHOD ............................................................................................ 19 4. PHYSICOCHEMICAL PROPERTY ESTIMATION .............................................. 20 4.1 Entropy of Boiling (∆Sb) ....................................................................................... 20 4.2 Differential Heat Capacity of Boiling (∆Cpb) ....................................................... 22 4.3 Entropy of Melting (∆Sm) ..................................................................................... 23 4.4 Differential Heat Capacity of Melting (∆Cpm) ..................................................... 25 4.5 Enthalpy of Boiling (∆Hb) .................................................................................... 26 4.5.1 Energy of Vaporization at 298K (∆Ev) ............................................................. 28 5 Table of Contents---Continued 4.6 Enthalpy of Melting (∆Hm) ................................................................................... 28 4.7 Boiling Point (Tb) .................................................................................................. 31 4.8 Melting Point (Tm) ................................................................................................ 32 4.9 Heat of Sublimation at 298K (∆Hsub) .................................................................... 34 4.10 Molar Volume (V) ................................................................................................ 35 4.11 Solubility Parameter (δ) ........................................................................................ 37 4.12 Fugacity Ratios (CLFR, GLFR) ........................................................................... 38 4.12.1 Gas-Liquid Fugacity Ratio (GLFR) ................................................................. 39 4.12.2 Crystal-Liquid Fugacity Ratio (CLFR) ............................................................ 39 4.13 Vapor Pressure (VP) ............................................................................................. 40 4.14 Activity Coefficient in Octanol (γo) ...................................................................... 42 4.15 Activity Coefficient in Water (γw) ........................................................................ 43 4.16 Solubility in Octanol (So) ...................................................................................... 45 4.17 Solubility in Water (Sw) ........................................................................................ 46 4.18 Air-Octanol Partition Coefficient (Kao) ................................................................ 47 4.19 Air-Water Partition Coefficient (Kaw) ................................................................... 48 4.20 Octanol-Water Partition Coefficient (Kow) ........................................................... 49 5. SUMMARY .............................................................................................................. 51 6. CONCLUSION ......................................................................................................... 54 7. APPENDIX A – SUPPLEMENTARY DATA......................................................... 55 REFERENCES ....................................................................................................... 113 6 LIST OF TABLES Table 1. UPPER Properties ............................................................................................... 12 Table 2. Molecular Descriptors for UPPER ..................................................................... 13 Table 3. Environmental designations of UPPER groups ................................................. 15 Table 4. Inter-correlation matrix for the molecular geometric factors ............................. 18 Table 5. Group contribution coefficients for calculation of the enthalpy of boiling ....... 27 Table 6. Group contribution coefficients for calculation of the total enthalpy of melting 30 Table 7. Group contribution coefficients for calculation of molar volume ...................... 36 Table 8. Group contribution coefficients for calculation of the activity coefficient in water ................................................................................................................... 44 Table 9: Summary of UPPER relationships for physicochemical property calculation .. 52 Table 10: Summary of UPPER calculation results .......................................................... 53 7 LIST OF FIGURES Figure 1. UPPER (Unified Physical Property Estimation Relationships) Scheme ........... 13 Figure 2. Calculated versus experimental entropy of boiling ........................................... 21 Figure 3. Calculated versus differential Heat Capacity of boiling .................................... 23 Figure 4. Calculated versus experimental total entropy of melting .................................. 25 Figure 5. Calculated versus experimental enthalpy of boiling ......................................... 28 Figure 6. Calculated versus experimental total enthalpy of melting ................................ 30 Figure