Energy-minimized structures

We used DFT to optimize the geometries of various Hammett bases on cluster models of zeolite Brpnsted sites. For p-fluoronitrobenzene and p-nitrotoluene, two indicators with strengths of ca. -12 for their conjugate acids, we saw no protonation in the energy minimized structures. Similar calculations using the much more strongly basic aniline andogs of these molecules demonstrated proton transfer from the zeolite cluster to the base. We carried out F and experimental NMR studies of these same Hammett indicators adsorbed into zeolites HY and HZSM-5. 

Most drug-like molecules adopt a number of conformations through rotations about bonds and/or inversions about atomic centers, giving the molecules a number of different three-dimensional (3D) shapes. To obtain different energy minimized structures using a force field, a conformational search technique must be combined with the local geometry optimization described in the previous section. Many such methods have been formulated, and they can be broadly classified as either systematic or stochastic algorithms. 

On this basis the porosity and surface composition of a number of silicas and zeolites were varied systematically to maximize retention of the isothizolinone structures. For the sake of clarity, data is represented here for only four silicas (Table 1) and three zeolites (Table 2). Silicas 1 and 3 differ in their pore dimensions, these being ca. 20 A and 180 A respectively. Silicas 2 and 4, their counterparts, have been calcined to optimise the number and distribution of isolated silanol sites. Zeolites 1 and 2 are the Na- and H- forms of zeolite-Y respectively. Zeolite 3 is the H-Y zeolite after subjecting to steam calcination, thereby substantially increasing the proportion of Si Al in the structure. The minimum pore dimensions of these materials were around 15 A, selected on the basis that energy-minimized structures obtained by molecular modelling predict the widest dimension of the bulkiest biocide (OIT) to be ca. 13 A, thereby allowing entry to the pore network. 

Figure 10 Overlay of energy-minimized structures of the E and Z isomers and WIN54954.

Figure 21 Comparison of volume map for HRV-14 generated from x-ray data (left) and small-molecule energy-minimized structures (right). 

Fig. I. (Left) Numbering of vinblastine-type alkaloids in this chapter according to the biogenetic scheme of LeMen and Taylor (134), with equivalent atoms in all synthetic intermediates equally labeled. (Right) Approximation of computer-generated, energy-minimized structure, obtained with the Clark Still MACROMODEL program.

Figure 4. Portion of the central helix in the energy-minimized structures of the crystalline DeS with the IdoA ring in (a),...

Figure 1. Given structure. a) Structure from literature b) Initial CAMD-generated structure c) Energy-minimized structure.

Attempts to isolate the ferrocenyl dendrimers described above in a crystalline form suitable for X-ray structural determination have so far been unsuccessful. For this reason, we have used computer-generated molecular models in order to gain further information about the structural features of these materials. Figure 3 illustrates an energy-minimized structure determined from CAChe molecular mechanic calculations of the ferrocenyl dendrimer 2. From these studies, we have measured approximate diameters of 2 run for the first-generation dendrimers 1,3, and 5, and 3 nm for the second-generation dendrimers 2,4, and 6. 

Figure 3.3 Energy minimized structure (PM3 method) of the CB7 MV2 + complex. (See the color version of this figure in Color Plates section.)...

Figure 3.3 Energy minimized structure (PM3 method) of the CB7 MV2+ complex. 

Figure 3.12 Energy-minimized structure (PM3) of the Fc 6 inclusion complex. 

When the guest used is p-nitrophenylcholine carbonate (PNPCC) the Lewis acid zinc(n) activates the well-positioned carbonyl group in the P PCC Zn-cavitand towards reactions with external nucleophiles. The energy minimized structure of the PNPCC Zn-cavitand complex shows that cation-n interactions and C —O -Zn coordination bond occurs simultaneously. 

Fig. 7. Energy-minimized structures of acetone and mesityl oxide adsorption complexes on a cluster model of HZSM-5 using DFT calculation. Note that in the case of the acetone complex, the proton remains bonded to the bridging oxygen, while in the case of the mesityl oxide complex, the proton is more fully transferred to the ketone. (Reprinted with permission from Haw et al. (7). Copyright 1996 American Chemical Society.)...

Figure 7 shows an overlay of the energy minimized structures for each of the compounds in Table 1. GT-2016, 2107, and 2158 all show good overlay of their... 

It is important to realize that for any arrangement of more than two atoms the strain energy minimized structure does not have ideal (zero strain) distances and angles. This is demonstrated in the case of ethane (Fig. 2.2), where, due to the repulsion of the protons, the experimentally determined C-C distance in ethane of 1.532 A, which is well reproduced by empirical force field calculations, is slightly longer than the ideal C-C separation of 1.523 A used in the MM2 force field1. Further examples are presented in Table 2.1. With increasing substitution of the carbon atoms the C-C separation increases up to 1.611 A in tris(t-butyl)methane. 

The energetics of isomer prediction using molecular mechanics is discussed in detail in Chapter 7. One of the results of such a study is the structure of each of the isomers.The archetypal studies in this field relate to the complexes [Co(dien)2]3+ (dien = 3-azapentane-l,5-diamine see Chapter 7). Other important studies include those on macrocyclic ligands (see also Chapter 8). Tetraaza macrocyclic ligands, for example, can adopt a series of configurational isomers, and these have been the subject of numerous molecular mechanics calculations. Consider an equatorially coordinated tetraaza macrocylce. Each of the amine groups can coordinate with the amine proton or substituent disposed above or below the coordination plane. How many isomers result depends on the symmetry of the macrocycle. For example, in the classic case of cyclam (cyclam - 14-ane-N4 = 1,4,8,11-tetraazacyclotetradecane) there are five isomers[12] and these are shown schematically in Fig. 6.3. It is not always possible to prepare or separate all of these isomers and, therefore, in many cases only a minority have been structurally characterized. Thus, the energy-minimized structures represent the best available three-dimensional representations of the other isomers. 

Structures determined by spectroscopic means are generally underdetermined in that the number of variables is similar to or greater than the number of observations. In such cases, the energy-minimized structures can be used to aid in the refinement of the structure or as a check on the geometry[51]. Applications of molecular mechanics modeling to the determination of solution structures is described in detail in Chapters 6, 7, and 9. Such approaches are fundamental to the determination of macromolecu-lar structures by NMR spectroscopy. 

Fig. 6 Energy-minimized structures of a photoisomerizable cyclic azobenzene polypeptide.

Fig. 18 Thermodynamically controlled synthesis of chiral host 34.127 Energy-minimized structures of 34 (MM2) are shown on the right. (For color version of this figure, the reader is referred to the web version of this book.)...

Fig. 2.1.10. Energy minimized structures of self-assembled [Cu (all-Sa)-ll 2]+-complex (MMFF-minimized, left) and of analogous covalently assembled tetra (BINOL) substituted spirobifluorene (all-S0)-12 (MM2-minimized, right).

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