Electronic parameter

Electronic properties of molecules [12, 40 — 43, 53, 57, 158, 294 — 297] can be described by a wide variety of different parameters, e.g. by Hammett ct constants, field and resonance parameters and pKa values, 

The use of a constants in QSAR studies started with the early finding of Hansen [13] that the toxicities of substituted benzoic acids against mosquito larvae are correlated with Hammett o values (Table 10) eq. 38 was derived after the p-nitro analog had been excluded (all analogs n = 14 r = 0.711 s = 0.427). 

Indeed, all analogs can be described much better by using n instead (eq. 39) [15]. The log 1/C vs. CT relationship in eq. 38 only exists by fortune. It results from a close relationship between n and a, if the nitro analog is excluded (n = 13 tt us. a r = 0.91) all equations were recalculated by using the rttenzene. and Op values presented in Table 10. 

Toxicity of substituted benzoic acids vs. mosquito larvae 

In considering electronic effects, one has to differentiate between field (inductive) effects and resonance effects. Due to the characteristic features of a benzene ring, mainly describes the inductive effect while stands for a combination of both effects, with the resonance effect predominating. Over the past decades many different a scales were developed in organic chemistry, besides a and Gp also (to account for substituents which donate electrons to the aromatic ring system by direct resonance interaction), (for corresponding acceptor substituents), a and ct (normal or unexalted a constants), a, and Gr (inductive and resonance contributions), etc. 

Obviously, compound properties such as partitioning between water and lipid phases will be different if they are (partly) dissociated. Accounting for ionization and dissociation of chemicals at ambient pH values by direct use of an electronic descriptor such as p is inadequate rather the relevant parameters (e.g. log P ) have to be adopted for the fractions of ionized/unionized species (Taylor, 1990 Kubinyi, 1993) for details, see section 1.2.3. 

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The electronic energy W in the Bom-Oppenlieimer approxunation can be written as W= fV(q, p), where q is the vector of nuclear coordinates and the vector p contains the parameters of the electronic wavefimction. The latter are usually orbital coefficients, configuration amplitudes and occasionally nonlinear basis fiinction parameters, e.g., atomic orbital positions and exponents. The electronic coordinates have been integrated out and do not appear in W. Optimizing the electronic parameters leaves a function depending on the nuclear coordinates only, E = (q). We will assume that both W q, p) and (q) and their first derivatives are continuous fimctions of the variables q- and py... 

C-nmr data have been recorded and assigned for a great number of hydantoin derivatives (24). As in the case of H-nmr, useful correlations between chemical shifts and electronic parameters have been found. For example, Hammett constants of substituents in the aromatic portion of the molecule correlate weU to chemical shifts of C-5 and C-a in 5-arylmethylenehydantoins (23). Comparison between C-nmr spectra of hydantoins and those of their conjugate bases has been used for the calculation of their piC values (12,25). N-nmr spectra of hydantoins and their thio analogues have been studied (26). The N -nmr chemical shifts show a linear correlation with the frequencies of the N—H stretching vibrations in the infrared spectra. 

Unsaturated sulfoncs (314,315) and nitroolcfins (303,315-317) also give alkylation products with enamines. In the latter reactions the formation of nitroethyl or cyclobutane derivatives has been found (316) to depend on the reaction medium as well as steric and electronic parameters which determine the fate of zwitterionic intermediates. Thus no enamine products could... 

The temperature-independent van der Waals parameters a and b are unique for each gas and are determined experimentally (Table 4.5). Parameter a represents the role of attractions so it is relatively large for molecules that attract each other strongly and for large molecules with many electrons. Parameter b represents the role of repulsions it can be thought of as representing the volume of an individual molecule (more precisely, the volume per mole of molecules), because it is the repulsive forces between molecules that prevent one molecule from occupying the space already occupied by another molecule. 

There will exist an equilibrium between the two states. If the ener between the two states, E, is of the order of kT, then the relative populations of the two states will vary with the temperature of the sample. In the Fe(III) dithiocarbamate series of complexes, [FeCRiRgdtcla], AE can be varied by suitable choice of substituents Ri and Rj. Although these are well removed from the FeSg molecular core, they can appreciably affect the electronic parameters of the central iron atom and of the surrounding crystal field of the sulfur atom by way of the conjugated system of the ligand (237). The results of the spin crossover are reflected in magnetic susceptibility data. 

Spectroscopic studies have been carried out on a number of benzo-1,2,3,4-tetrazine 1,3-di-iV-oxides 98 and furazanotetrazine 1,3-di-iV-oxide 99 to investigate their characteristic vibration frequencies and electronic parameters <95MC100>. 

The next step in the development of the extrathermodynamic approach was to find a suitable expression for the equilibrium constant in terms of physicochemical and conformational (steric) properties of the drug. Use was made of a physicochemical interpretation of the dissociation constants of substituted aromatic acids in terms of the electronic properties of the substituents. This approach had already been introduced by Hammett in 1940 [14]. The Hammett equation relates the dissociation constant of a substituted benzoic acid (e.g. meta-chlorobenzoic acid) to the so-called Hammett electronic parameter a ... 

Lipophilicity (log P), Hammett electronic parameter (a) and inhibitory concentration (ICj,) for oxidative phosphorylation of 11 doubly substituted salicylanilides [17], The two substitution positions are labeled A and B. 

A table of correlations between seven physicochemical substituent parameters for 90 chemical substituent groups has been reported by Hansch et al. [39]. The parameters include lipophilicity (log P), molar refractivity MR), molecular weight MW), Hammett s electronic parameters (a and o ), and the field and resonance parameters of Swain and Lupton F and R). 

Physicochemical and biological parameters obtained from 6 oxazepine (X = O) and 6 thiazepine (X = S) neuroleptics. These include Hammett s electronic parameter (o ), lipophilicity (log P) and its squared value, and the activities (log l/EDjn) in two pharmacological tests in rats [41]. 

Our objective has been to develop methods that allow the calculation of various electronic parameters such as partial atomic charge, q, electronegativity, polarizability, a, for each atom of a molecule. In this way, the values assigned to an atom not only reflect the type of the atom, but also the particular molecular environment into which this atom is embedded (Fig. 18). The electronic parameters assigned to the atoms of a bond will then be used to arrive at a quantitative value for this bond which reflects its reactivity. A detailed description of a reaction will also have to include parameters characteristic of the reagent in order to account for its influences on bond breakage and formation. 

An alternative approach was introduced by Car and Parrinello [12], who developed a DFT-MD method to study periodic systems using a planewave expansion in which the electronic parameters, as well as the nuclear coordinates, are treated as dynamical variables. Following the Car and Parrinello... 

The technique can be used either to perform geometry optimization, by simultaneously annealing the wavefunction and the geometry, or to simulate real dynamics, if the temperature of the fictitious (electronic) parameters is kept close to zero. A drawback of the method is that small masses must be chosen for the electronic parameters in order to achieve an adiabatic separation of the nuclear and the fictitious parameter motions. As a consequence, time steps smaller than MD simulations involving only nuclear motion, are required. 

It is seen how all indicators of aromaticity correctly predict that a structure close to the TS is the most aromatic species along the reaction path, except HOMA and FLU indices, that are unsuccessful to account for the aromaticity of the TS. The reason for the failure of HOMA and FLU is that both values measure variances of the structural and electronic patterns, respectively, with respect to a reference value. Therefore, HOMA and FLU might fail if they are not applied to stable species because, while reactions are occurring, structural and electronic parameters suffer major changes. It is worth noting that the isotropic NICS(O) and NICS(l) values of the TSs are larger than those of benzene, but this is not the case with the more sophisticated NICS indices. 

For monodentate ligands, e.g., triphenylphosphane, Tolman s cone-angle 0 and the electronic parameter x have a significant influence on the activity and the selectivity of the resulting catalyst system [24,25]. As regards bidentate ligands, which provide two coordination centers for the transition metal, the so-called bite angle fi determines the selectivity of the formed aldehydes. 

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