Bond, rotation about

No molecule is completely rigid and fixed. Molecules vibrate, parts of a molecule may rotate internally, weak bonds break and re-fonn. Nuclear magnetic resonance spectroscopy (NMR) is particularly well suited to observe an important class of these motions and rearrangements. An example is tire restricted rotation about bonds, which can cause dramatic effects in the NMR spectrum (figure B2.4.1). 

Before considering the special case of rotation about bonds in polymers it is useful to consider such rotations in simple molecules. Although reference is often made to the free rotation about a single bond, in fact rotational energies of the order of 2kcal/mole are required to overcome certain energy barriers in such simple hydrocarbons as ethane. During rotation of one part of a molecule about... 

If two different three-dimensional arrangements in space of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are called conformationsIf they are not interconvertible, they are called configurations Configurations represent isomers that can be separated, as previously discussed in this chapter. Conformations represent conformers, which are rapidly interconvertible and are thus nonseparable. The terms conformational isomer and rotamer are sometimes used instead of conformer . A number of methods have been used to determine conformations. These include X-ray and electron diffraction, IR, Raman, UV, NMR, and microwave spectra, photoelectron spectroscopy, supersonic molecular jet spectroscopy, and optical rotatory dispersion (ORD) and CD measurements. Some of these methods are useful only for solids. It must be kept in mind that the conformation of a molecule in the solid state is not necessarily the same as in solution. Conformations can be calculated by a method called molecular mechanics (p. 178). 

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. 

The very efficient di-rr-methane rearrangement from the triplet state in this case is probably due to two factors (a) the energetics is favorable for cleavage of bond 3-4 and formation of bond 2-4 [see Eq. (8.26)] and (b) rotation about bond 1-2, cis-trans isomerization, should be restricted because of steric interactions. 

Rotation about Bonds involving Carbon Atoms in a State of sp2 Hybridisation... 

Rotation about Bonds involving carbon aatoms in a state of sp2 hybridisation... 

Rotations about bonds with partial tt character... 

The conformations of molecules are interconvertible by internal rotations about bond axes. A conformation of a molecule with n atoms can be represented by a family of... 

Proceeding from G1 with the E)/ E) conformation to G2 with (Z)/(Z) implies a rotation about bonds b and b as indicated by the bold lines in Fig. 29. As the centres of atropisomerism on each half of the molecule are not affected by this rotation, the projection of the side-chains must be adjusted such that the projections correspond to retainment of the original configuration. The assignment of the peaks is made using the pattern interchange given earlier in Fig. 8. 

The nmr data for this type of motion are direct and the motion clearly involves rotation about bonds in the millisecond time scale range. However. less direct evidence for motion comes from other techniques such as fluorescence depolarization, 02 diffusion, hydrogen exchange kinetics, and nmr relaxation times (see Ref. 4). The extent of this motion is not yet easy to define, but this evidence points to motion in the nanosecond time scale range. It is tempting to see the motion in this time scale as bond oscillations rather than rotations. To put it in a different way, on this time scale the side chains have some freedom to move with respect to each other but not normally to undergo substantial bond rotation. Table IV summarizes some references for motion of different types. Additionally, nmr relaxation studies suggest that the backbone or main chain of a protein is more restricted than that of the side chains. 

To describe the steric arrangement of the atoms in a molecule, in addition to bond lengths we need to know something about the angles between the bonds, the sizes of the atoms, and their freedom to move within the molecule, (e.g., rotations about bonds). 

RGURE 8-18 Structural variation in DNA. (a) The conformation of a nucleotide in DNA is affected by rotation about seven different bonds. Sx of the bonds rotate freely. The limited rotation about bond 4 gives rise to ring pucker, in which one of the atoms in the five-membered furanose ring is out of the plane described by the other four. This conformation is endo or exo, depending on whether the atom is displaced to the same side of the plane as C-5 or to the opposite side (see Fig. 8-3b). (b) For purine bases in nucleotides, only two conformations with respect to the attached ribose units are sterically permitted, anti or syn. Fyrimidines generally occur in the anti conformation. 

If two different three-dimensional arrangements of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are conformations otherwise, they are configurations. Configurations represent isomers that can be separated however, conformers cannot be separated. Conformational effects on reactivity may be considered under the steric effects. 

Concerning conformation , we prefer to adopt a broader definition than has generally been used heretofore. Excluding normal molecular vibrations, relative atomic motion that breaks no bonds within a molecular framework generates conformations. A usual definition which specifies that conformations are attained by rotations about bonds is far too restrictive, considering that the conversion of one chair form of cyclohexane to another involves several complicated coupled rotations and 11... 

We can draw two nonsuperimposable mirror images of the most stable chair conformation of trans-1,2-dibromocyclohexane with both bromines equatorial. These structures cannot interconvert by ring-flips or other rotations about bonds, however. They are mirror-image isomers enantiomers. 

This observation is used in practice when NMR spectra give poor results because of slow rotation about bonds. Amides of many kinds, particularly carbamates, show slow rotation about the C-N bond at room temperature because of the amide delocalization. These amides have bigger barriers to rotation than the 70 kj mol-1 of the example in the table. The result is a poor spectrum with broad signals. In this example, the two sides of the five-membered ring are different in the two rotational isomers and give different spectra. 

Changing the conformation of a molecule means rotating about bonds, but not breaking them... 

In a number of cases, these two types of interconversion may be brought about as well by rotation about bonds, e.g. rotation about the (X,Y,Z)-N single bonds or the X=N double bond. This situation holds, for instance, in acyclic amines (methylamine, hydroxylamine. ..) and in imines. Furthermore, nitrogen inversion may in some cases occur in the same molecule together with ring inversion, for instance, in piperidine. It will thus sometimes be necessary to distinguish between internal... 

Nucleosides and Nucleotides occur in a limited number of preferred conformations. Except for the planar purine or pyrimidine base, the nucleotide component of the nucleic acids contains only single bonds (see Fig. 17.1). Rotation about bonds is restrained by the requirements of the furanose ring closure, and for the acyclic bonds, rotation is restricted by electronic factors and is limited by intramolecular interactions. Therefore only a few conformations have to be considered if nucleosides and nucleotides are described in their three-dimensional shapes. 

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