Variable substitution position

Table 37.3 shows the complete table of eight indicator variables for 10 triply substituted tetracyclines [31 ] that have been tested for bacteriostatic activity (1/Z), which is defined here as the ratio of the number of colonies grown with a substituted and with the unsubstituted tetracycline. In this application we have three substitution positions, labelled U, V and W. The number of substituents at the three sites equals 2,3 and 3, respectively. Arbitrarily, we chose the compound with substituents H, NOj and NO2 at the sites U, V and W as the reference compound. This leads to a reduction of the number of indicator variables from eight to five, as shown in Table 37.4. The solution of the Free-Wilson model can be obtained directly by means of multiple regression ...

Starting with the semiempirical approach of Kauzmann et al. (16), Ruch and Schonhofer developed a theory of chirality functions (17,18). These amount to polynomials over a set of variables that correspond to the identity of substituents at various substitution positions on a particular achiral parent molecule. The values of the variables can be adjusted so that the polynomial evaluates to a good fit to the experimentally measured molar rotations of a homologous series of compounds (2). Thus, properties 1 and 2 are satisfied, but the variables are qualitatively distinct for the same substituent at different positions or different substituents at the same positions, violating property 3. Furthermore, there is a different polynomial for each symmetry class of base molecule. Thus, chirality functions are not continuous functions of atom properties and conformation (property 4). 

Examination of the properties of N-borane adducts, e.g., 90, of piperidine, substituted piperidines and various other N-containing six-membered ring heterocycles constitutes an alternative approach to variable temperature NMR spectroscopy in that borane can be used as a locking agent for the observation of preferred conformers (cf. Scheme 35). In addition, the adducts can be very helpful for the assignment of the chemical shifts of the other substituents in the molecule as well as to acertain the configuration at the substituted positions (91T6903). 

In contrast to the r -methcxl, where unsubstituted atomic positions are indeterminable, r0-derived methods can locate also unsubstituted atoms, although with less accuracy than for substituted positions. In practical cases, this capacity is limited to one or two unsubstituted atoms and yields useful results only when the SDS is otherwise large enough. Coordinates that are (for whatever reason) not included in a r0-type fit must be assigned estimated values, which are kept fixed in the fit but affect the result. In these cases, one should not do so without also setting error limits to these coordinates in order to find out, by Eq. 30, which additional errors of the positions are due to the error afflicted fixed positions. If symmetrically equivalent atomic positions are among those kept fixed, the relations established between the independent and the expanded set of variables (Eq. 56b) now denoted as B(A) and B, respectively, are applicable in the form ... 

Lithiation of aziridines followed by electrophilic substitution continues to be explored as a means of accessing variably substituted aziridines. l-Alkyl-2-oxazolinylaziridines were reported to undergo a- and/or p-lithiation depending on the steric demand of the nitrogen substituent <07OL3295>. Despite the presence of a more acidic hydrogen at the a-position, 1-trityl-2-oxazolinylaziridine 49 underwent exclusive p-lithiation due to steric reasons, whereas a-lithiation was exclusively observed for l-benzyl-2-oxazolinylaziridine 50. 

Aldehydes, arylideneanilines, carboxylic acids and orthoesters have been used as one-oarbon units for binding the two amino functions of 4-amino-l-alkyl-3-propylpyrazole-5-oarboxamide to give l,6-dihydro-pyrazolo[4,3-<7]pyrimidin-7-ones <05MC619 05JHC751>. A modified efficient synthesis of variably substituted pyrazolo[4,3-<7]pyrimidm-7-ones has been described using a pyrazole-5-carboxylic acid, which was selectively brominated at position 4 and then converted into the carboxamide. Microwave irradiation gave better yields in the conversion of the carboxamides to pyrazolo[4,3-J]pyrimidinones <05JHC1085>. 

These two systems are equivalent. Let us look at the equivalence of variables. The computer-generated equations from the bond graph use different sets of state variables. Substituting the physical variable definitions of the bond graph variables, position (q) and momentum p), in the bond graph system should produce the other state variable system. Consider then the first row of (11.19) equation (11.14) should be equivalent to (11.7) ... 

In Scheme IV, intranuclejar activation is depicted. Kinetic studies with ionic nucleophiles show a variable relationship between the rates of reaction ortho and para to an azine-nitrogen (348 vs. 353 or 349) or nitro group due to entropy effects the energy of activation is expected on further study to be consistently lower for the para-position. The relative reactivity of 2- and 4-substituted bicyclic azines... 

Variable results have been reported for the halogenation of thieno[2,3-6]quinoline (123). Initial attack was mainly at the 3-position, but it was difficult to avoid the formation of 2,3-dihalogenated products, even when only 1 mol of halogen was used (predictions are for 2- and 3-substitution [77ZN(B)1331]). Bromine buffered in chloroform gave the 3-monobromo derivative, but analogous chlorination gave a mixture that included some... 

When aromatic nitro compounds are treated with cyanide ion, the nitro group is displaced and a carboxyl group enters with cine substitution (p. 854), always ortho to the displaced group, never meta or para. The scope of this reaction, called the von Richter rearrangement, is variable. As with other nucleophilic aromatic substitutions, the reaction gives best results when electron-withdrawing groups are in ortho and para positions, but yields are low, usually < 20% and never > 50%. 

The analysis of Table 31.2 by CFA is shown in Fig. 31.11. As can be seen, the result is very similar to that obtained by log double-centering in Figs. 31.9 and 31.10. The first latent variable expresses a contrast between NO2 substituted chalcones and the others. The second latent variable seems to be related to the electronic properties of the substituents. The contributions of the two latent variables to the total inertia is 96%. The double-closed biplot of Fig. 31.11 does not allow a direct interpretation of unipolar and bipolar axes in terms of the original data X. The other rules of interpretation are similar to those of the log double-centered biplot in the previous subsection. Compounds and methods that seem to have moved away from the center and in the same directions possess a positive interaction (attraction). Those that moved in opposite directions show a negative interaction (repulsion). 

Although the number of actinides is the same as that of the lanthanides, their availability and chemical characteristics have so far largely restricted the study of their ligand substitution mechanisms to dioxouranium(VI), which is the ionic form of uranium most amenable to such studies in solution. In the solid state, the oxo ligands occupy axial sites above and below the U(VI) center, and four (328), five (329, 330), and six (331, 332) oxygen donor atoms have been reported to occupy equatorial positions. From a mechanistic point of view, this variability of the occupancy of the equatorial plane suggests the possibility of both d- and a-activated ligand substitution pro-... 

It can be assumed a priori [11] that the reason for the variable composition of the octachloroditechnetates may be either a variable oxidation state of technetium or substitution of some of the cations by H30+ ions. The first explanation was proposed [22], when the accuracy ( + 0.017 A) of the X-ray diffraction study by a photomethod [81] precluded the determination of the fine difference between the Tc-Tc distances in the [Tc2CI8]3- and [Tc2Cl8]2- anions, which is 0.03 A according to the latest X-ray diffraction data [11,35,60,63,82] (Table 1). An attempt was made [11] to determine the H30+ ions in potassium octachloroditechnetate, which led to their detection from the weak characteristic absorption lines in the infrared spectra (v OH) = 2965,2930, and 2865 cm-1 <5(HOH) = 1610 cm-1 [83,84]). The results [11] did not conflict with the revised X-ray diffraction data [82] according to which the K+ ions in the unit cell of potassium octachloroditechnetate (+ 2.5) are present in two non-equivalent positions sixfold (K ) and threefold (K") under these conditions, the sixfold positions were fully occupied by K+ ions, while the threefold positions were half-occupied. 

Fig. 4.16. The A dynamics method for alchemical transformations was developed by Guo and Brooks [57] for rapid screening of binding affinities. In this approach the parameter A is a dynamic variable. Techniques like ABF or metadynamics [34] can be used to accelerate this type of calculation. A dynamics was used by Guo [57] to study the binding of benzamidine to trypsin. One simulation is sufficient to gather data on several benzamidine derivatives. Substitutions were made at the para position C5 (H, NH2, CH3 and Cl). The hydrogen atoms are not shown for clarity...

Wilson et al. [27] showed that the introduction of steric hindrance in the 6-position of one or two of the pyridine groups was sufficient to fine-tune the ligand field and obtain crossover compounds. These systems have been investigated using a number of different techniques, both in the solid and solution phases. Thermodynamic parameters have been derived from variable temperature magnetic susceptibility data for the single methyl-substituted (23 ) (AH°=19.7 kj mol"1, A5°=39.8 J mol"1 K"1), the double methylsubstitut-... 

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