Conformation in solution

Conformational Adjustments The conformations of protein and ligand in the free state may differ from those in the complex. The conformation in the complex may be different from the most stable conformation in solution, and/or a broader range of conformations may be sampled in solution than in the complex. In the former case, the required adjustment raises the energy, in the latter it lowers the entropy in either case this effect favors the dissociated state (although exceptional instances in which the flexibility increases as a result of complex formation seem possible). With current models based on two-body potentials (but not with force fields based on polarizable atoms, currently under development), separate intra-molecular energies of protein and ligand in the complex are, in fact, definable. However, it is impossible to assign separate entropies to the two parts of the complex. 

In addition to existing as helices in crystals, there is evidence that certain vinyl polymers also show some degree of regular alternation between trans and gauche conformations in solution. In solution, the chain is free from the sort of environmental constraints that operate in a crystal, so the length of the helical sequence in a dissolved isotactic vinyl polymer may be relatively short. 

Dextrose in solution or in soHd form exists in the pyranose stmctural conformation. In solution, a small amount of the open-chain aldehyde form exists in equiUbrium with the cycHc stmctures (1) and (2). The open-chain form is responsible for the reducing properties of dextrose. 

Annulene, [22]annulene, and [24]annulene have all been reported. The NMR spectrum of [22]annulene is consistent with regarding the molecule as aromatic, whereas those of the [20] and [24] analogs are not. In each case, there is some uncertainty as to the preferred conformation in solution, and the NMR spectra are temperature-dependent. Although the properties of these molecules have not been studied as completely as those of the smaller systems, they are consistent with the predictions of the Huckel rule. 

A study of the relative stability of tra 5-2-azidothiazole 32b with respect to the corresponding cis conformer 32a showed that 32b is destabilized in the gas phase but appears to be the more stable conformer in solution (Scheme 23). The stability increases with increasing polarity of the solvent [98JA4723]. 

The value of a for the trans, tra s-5-substituted 2,4-pentadienoic acids suggests that the conformation in solution is the s-trans (between C and C ). Rough estimates give a value of a of about. 8 for the s-trans and of about 1.0 for... 

This measures how much the molecule prefers the conformation it adopts in the binding site compared to its conformation in solution. 

It is important to note that most molecules are not rigid but may prefer a distrinct structure and the conformation of a molecule strongly depends on its specific environment. Hence, the crystal structure of a drug does not have to correspond to the receptor bound conformation. Also, a conformation in solution depends on the nature of the solvent and measuring conditions, and may change when the molecule is bound to the receptor [4]. In addition, different receptors or receptor subtypes can bind the same drug in different conformations. It is a general assumption and observation, but by far not a strict condition, that the conformation in aqueous solution is similar to the bound conformation and is a better representation of the bioactive conformation than an X-ray structure of the isolated molecule in the crystalline state. 

It is known that polymer dynamics is strongly influenced by hydrodynamic interactions. When viewed on a microscopic level, a polymer is made from molecular groups with dimensions in the angstrom range. Many of these monomer units are in close proximity both because of the connectivity of the chain and the fact that the polymer may adopt complicated conformations in solution. Polymers are solvated by a large number of solvent molecules whose molecular dimensions are comparable to those of the monomer units. These features make the full treatment of hydrodynamic interactions for polymer solutions very difficult. 

The zinc nitrate complexes of pyridyl functionalized 12[ane]N3 ligands l-(2-pyridylmethyl) -1,5,9-triazacyclododecane and l-(2-pyridyl-2 -ethyl)-l,5,9-triazacyclododecane were formed. 13C NMR studies were used to determine conformation in solution suggesting the former gave a trigonal bipyramidal isomer in solution with a water bound and the latter gave a 2 1 mixture of tetrahedral and asymmetric trigonal bipyramidal isomers. The crystal structure of the zinc complex of l-(2-pyridyl-2 -ethyl)-1,5,9-triazacyclododecane reveals a tetrahedral geometry in the solid state.679... 

Diazaphosphorinanes exist as a mixture of three conformers in solution [Eq. (51)], although all heteroatoms in the ring have substituents. Conformational equilibrium is due to the low inversion barrier of nitrogen studied by H NMR and the dipole moment method (83MI1 84MI1) [Eq. (51)]. The results are presented in Table III. 

Both ORD and CD are important tools in the study of molecular conformation in solution. These techniques are of special importance in the study of biomolecules, their helical content, and helix-coil transitions. 

Ervatamine (44) had a different conformation in solution with respect to 45 and 50. This was deduced from the different rate of N-methylation and from a careful inspection of 1 H-NMR spectra. These studies led to proposed conformation 270 for 44 and conformations 271a,b for 45 and 50, respectively. 

Three main characteristics emerge from these data. First, silks with different functions appear to have different conformations in solution second, we observe an inverse temperature transition to a /(-sheet or /(-turn like state and finally, silk crystallization requires temperatures that are much lower than those required for typical synthetic polymers. 

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