Synthesis of Amines Last time we completed our study of carbohydrates. Now we are turning our attention to another important class of organic compounds, amines. Many important drugs are amines, the bases present in RNA and DNA are amines, and the fundamental building blocks of proteins are amino acids.
One way to assess hydrogen bonding strength experimentally is the measurement of hydrogen bonding equilibrium constants: The applicability of these descriptors has been enhanced by an empirical calculation method based on a group contribution approach.
However, this approach can be erroneous for druglike molecules, which are usually larger compounds with various chemical functions. Intramolecular hydrogen bonding may be difficult to account for by a group contribution approach. Hydrogen bond donor acidity and acceptor basicity scales can also be obtained by quantum chemistry methods.
Another possible way to obtain hydrogen bond activities is to investigate the thermodynamics of hydrogen complex formation. Lipophilicity of a given compound is reported to be partly explained by its hydrogen bonding ability. This can be used to estimate hydrogen bonding ability by comparing the partition coefficients between water and different lipophilic phases, which need to be different in respect to their hydrogen bonding ability.
However, this approach is very difficult if not impossible for less lipophilic compounds, because of low partitioning into the heptane or cyclohexane phase. The data set mentioned above was also studied by Van de Waterbeemd et al.
Since then, various different definitions for polar surface area have been used. The value for PSA will differ depending on what type of surface is calculated e.
Nitrogen, oxygen and attached hydrogen atoms usually define a polar surface area, although sulfur atoms have been suggested as well. The type of the calculated surface is especially important if cut-offs from the literature are to be used in other settings: For flexible molecules it may also be of interest to obtain a dynamic polar surface area from all relevant, low-energy conformations weighted by the Boltzman distribution.
However, it has been shown that the static polar surface area derived from one reasonable conformation alone, in general, gives very similar results to the computationally much more costly dynamic PSA.
It has also been proposed that an indicative PSA can be derived from the 2D structure alone.
However, the relative PSA is more related to lipophilicity than to hydrogen bonding, whereas the absolute PSA represents the possible polar interactions in water and is, therefore, related to the energy necessary for desolvation.
Another way to describe hydrogen-bonding properties theoretically is the combination of calculated atomic charges with other molecular properties. A slightly changed descriptor, the sum of the partial charges of all hydrogen atoms connected to a noncarbon atom, was later found to correlate highly to other hydrogen bond descriptors for drug molecules.
Charge weighted molecular or partial surfaces, as introduced by Jurs et al. It has been found that simple counting descriptors may give a good enough correlation to interesting ADME properties, e. Such counting descriptors for hydrogen bonding are the number of hydrogen bond donors and acceptors, which can be defined either as donor and acceptor atoms or as donor hydrogen atom and acceptor electron pair.'The hydrogen bond is an attractive interaction between a hydrogen atom from a molecule or a molecular.
fragment X–H in which X is more electronegative than H, . Pearson, as an active contributor to the biology learning community, is pleased to provide free access to the Classic edition of The Biology Place to all educators and their students.
Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers – specifically polypeptides – formed from sequences of amino acids, the monomers of the polymer.
A single amino acid monomer may also be called a residue indicating a repeating unit of a polymer. Proteins form by amino acids undergoing condensation reactions, in . The N-H bonds in amines are somewhat polar.
As we might guess from considering electronegativities (estimated from positions in the periodic table), the N-H bond is more polar than the C-H bond and less polar than the O-H bond. Mar 25, · The importance of the hydrogen bond in protein structure can hardly be overemphasized”; and they suggested that each hydrogen bond would contribute 5 kcal mol −1 to the stability of the uniquely defined configuration.
1 Fifteen years later. Role of Hydrogen Bonding on Protein Secondary Structure Introduction The function and chemical properties of proteins are determined by its three-dimensional.