TLSER descriptors

Theoretical Linear Solvation Energy Relationship (TLSER) With the LSER descriptors of Kamlet and Taft in mind, Famini and Wilson developed QM-derived parameters to model terms in Eq. [18] and dubbed these the TLSER descriptors. Descriptor calculations are done with the MNDO Hamiltonian in MOPAC and AMP AC. MNDO has greater systematic errors than do AMI and PM3, but the errors tend to cancel out better in MNDO-derived correlation equations. A program called MADCAP was developed to facilitate descriptor calculation from MOPAC output files. 

For the same large set of compounds used in deriving Eq. [21], the gas-water distribution coefficient, (unitless), for a set of 423 compounds at 298 K was correlated with the set of TLSER descriptors resulting in Eq. [27]. (The subscript 2 refers to solvent parameters.)... 

Here, a is the polarizability related through TLSER descriptors by a = 7t 12 Vnic- The physical meaning of Eq. [31] is indicated by the negative sign on the polarizability term. Increased polarizability would increase the dispersion type intermolecular interactions and, thus, decrease the vapor pressure. 

Of particular interest is the analysis of other, experimentally determined empirical solvent polarity scales by means of the theoretically derived TLSER equation (7-67). For example, correlation of the solvatochromic Ej scale [see Eq. (7-29) in Section 7.4] with the TLSER descriptors of Eq. (7-67) leads to Eq. (7-68) for n = 29 solvents, with r = 0.937 and S = 0.075 [351] ... 

QSAR method based on the philosophy of the -> Linear Solvation Energy Relationships, whose empirically derived molecular descriptors are substituted hy descriptors defined in the framework of - computational chemistry [Famini et ai, 1991 Famini et ai, 1992 Famini and Wilson, 1994a]. The TLSER descriptors were developed with the aim of optimally correlating with LSER descriptors, thereby being as generally applicable to solute/solvent interactions as are the LSER descriptors. 

The TLSER descriptors have been used to estimate a range of properties including retention indices [Donovan and Famini, 1996], gas phase acidity [Famini et ai, 1993], and toxicological indices and biological activities [Wilson and Famini, 1991 Sixt et ai, 1995 Famini etal, 1998]. 

Two other types of descriptor have been included recently to help describe dipolarity and the possibility of multiple ligands. The molecular dipole moment, p, has been found to be insignificant in these TLSER correlations consequently, it was not included in the overall set of descriptors. However, it is possible to define local dipole moments in terms of atomic charges and interatomic distances, Eq. [25]. 

The TLSER correlations have charges in place of the LSER dipolarity/ polarizability, The interesting thing to note is that isozyme A involves a positive charge parameter, and isozyme B involves a negative charge parameter. A partial explanation for this peculiarity is that the two charge descriptors happen to correlate with each other (r= 0.76). 

Using a set of 479 compounds, Liang and Gallagher correlated the vapor pressure, p (Torr), at 298 K with the TLSER related descriptors to obtain Eq. [31]. Only a single descriptor was needed to provide a respectable result. 

In analogy with solvatochromic parameters but based on quantum theoretical chemistry, a set of - quantum-chemical descriptors intended to describe the hydrogen bonding effects of molecules by theroretical linear solvation energy relationships (TLSER) were proposed. 

Quantum-chemical descriptors are used in several QSAR approaches, such as, for example, theoretical linear solvation energy relationships (TLSERs), - Mezey 3D shape analysis, - GIPF approach, - CODESSA method, -> ADAPT approach. 

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