ConFirm conformational searching

Small-angle neutron scattering (SANS) studies of polyradical 50 in THF-dg at 170 K (slightly above melting point of the solvent) revealed the molecular structure (Fig. 31), which was analogous to that obtained from conformational searches.94 Since SANS is a relatively low-resolution technique and the information content of the data is rather low, the structure of 50 might be best described as dumbbell-like with overall dimensions of 2 x 3 x 4nm. Also, this result confirms that polyradical 50 existed as a monomer in solution at low temperatures. 

A conformational analysis of both protonated and unprotonated forms of the compound was performed using standard conformational search protocols in Maestro. This confirmed that only a very limited number of conformations were accessible to the molecule, with a number of energy equivalent variants for the piperidine chair. Conformations with a twist boat for the piperidine came in with a higher energy and were therefore discounted. Of these conformations, the lowest energy was selected and subjected to a further optimization using a semiempirical (AMI) approach in Spartan and is illustrated in Figures 12.6. 

Early discussions of the conformational equilibrium in Tachy have settled on the tEc and the tEt conformers as the most energetically favored, with the former being more abundant. A recent molecular mechanics-based (MMX) conformational search confirms the placing of tEc as the most abundant Tachy conformer (63%) but predicts cEc (18%) to be slightly more abundant than tEt (13%). The weak structureless band at the onset of the UV spectrum of HOTachy, Figure 27.8, should then be assigned to either the cEc or the tEt conformer, or both, and 254 nm should favor tEc-HOTachy excitation (note that s-cis diene moieties normally absorb to the red of s-trans diene moieties). The s-cis-butadiene moiety in tEc-HOTachy may explain the much lower HOTachy to HOPre quantum yield at 254 nm than... 

By default, ConFirm s fast search outputs a maximum number of 256 conformations per molecule within an energy range of 20 kcal/mol with respect to the estimated global minimum. Some results obtained with ConFirm are discussed in Sec. 6. 

As already mentioned in Sec. 5.1.1, ConFirm s best mode uses a distance geometry approach to generate initial conformations for a subsequent geometry optimization and energy minimization step. Thus, also the cyclical portions are fully included in the search procedure and are not taken from a library of predefined ring geometries. 

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