Modeling of Ion Complexation and Extraction Using Substructural Molecular Fragments

Abstract

A substructural molecular fragment (SMF) method has been developed to model the relationships between the structure of organic molecules and their thermodynamic parameters of complexation or extraction. The method is based on the splitting of a molecule into fragments, and on calculations of their contributions to a given property. It uses two types of fragments: atom/bond sequences and "augmented atoms" (atoms with their nearest neighbors). The SMF approach is tested on physical properties of C2-C9 alkanes (boiling point, molar volume, molar refraction, heat of vaporization, surface tension, melting point, critical temperature, and critical pressures) and on octanol/water partition coefficients. Then, it is applied to the assessment of (i) complexation stability constants of alkali cations with crown ethers and phosphoryl-containing podands, and of beta-cyclodextrins with mono- and 1,4-disubstituted benzenes, and (ii) solvent extraction constants for the complexes of uranyl cation by phosphoryl-containing ligands.

New Approach for Accurate QSPR Modeling of Metal Complexation: Application to Stability Constants of Complexes of Lanthanide Ions Ln3+, Ag+, Zn2+, Cd2+ and Hg2+ with Organic Ligands in Water

“…SMF [23,30,54,72] as subgraphs of molecular graphs of the ligands were used as descriptors in QSPR models. Molecules were represented with implicit hydrogen atoms.…”

“…Molecules were represented with implicit hydrogen atoms. Two classes of the SMF [70] [ 71] descriptors were generated: shortest topological paths with explicit representation of atoms and bonds, and terminal groups as shortest paths but defined by length and explicit identification of terminal atoms and bonds [23,30,33,43] (Figure 2). Single, double and triple bonds were considered different in acyclic and cyclic non-aromatic motifs.…”

“…[23,30,33,46,73] MLR is applied to build linear relationships between independent variables (SMF descriptors: X i , i =1, 2,…) and a dependent variable (here target property Y = logK): Y = c 0 + Σc i X i , where every descriptor value (SMF count x ij , j = 1, 2,…, n; here n is the number of ligands) is associated with observed property value (y j , j = 1, 2,…, n), c i is descriptor contribution, and c 0 is the independent term which is omitted in a part of models. The Singular Value Decomposition method is used to fit contributions c i and to minimize the sum of squared residuals which are squared differences between the property values calculated by the model (y j , calc ) and observed values (y j , exp ) in the training set.…”

“…[15][16][17][18][19][20][21] This opens an opportunity to develop quantitative structure -property relationships (QSPR) linking the stability constants with the structure of ligands which, in turn, can be used for computeraided design of new metal binders. [22,23] To date, QSPR modeling of stability constants of the metal -ligand complexation was performed for alkali, [24][25][26][27][28][29][30][31][32] alkaline-earth, [32][33][34][35][36][37][38] rare-earth [39][40][41][42] and transition metal [23,34,36,37,40,[43][44][45] ions. In many cases the practical application of the reported QSPR is complicated due to the lack of complete information about descriptors' calculations and details of machine-learning method implementation.…”

“…In many cases the practical application of the reported QSPR is complicated due to the lack of complete information about descriptors' calculations and details of machine-learning method implementation. In order to overcome this problem, we have developed the COMET (COmplexation of METals) software [39] which implements previously elaborated QSPR models of stability constants (logK) of the 1:1 (M:L) complexes of diverse organic ligands with alkaline-earth (Sr 2+ , [33,35] , and UO 2 2+ [43] ) in water at 298 K and an ionic strength 0.1 M. All these models are based on substructural molecular fragments (SMF) [23,30,33] representing a subtype of the ISIDA descriptors. [46] SMF are subgraphs of molecular graph [30,47] whereas fragment occurrences are descriptor values.…”