Lecture 5 Part 2 Flashcards
Give 4 examples of weakly basic drugs
cyclizine
imipramine
meperidine
ephedrine
give 4 examples of weakly acidic drugs
phenobarbital
aspirin
penicillin G
sulfadiazine
hydrogen bonds are formed between hydrogens attached to ________ and a _____
hydrogens attached to an electronegative donor atom (O,F,N) and an electronegative or basic acceptor (carbonyl oxygen)
what is the most common donor in the case of hydrogen bonds?
what is the most common acceptor in the case of hydrogen bonds?
most common donor = N-H
most common acceptor = carbonyl oxygen
in the case of hydrogen bonds….
the more electronegative the acceptor and the more electropositive the hydrogen……
THE SHORTER AND STRONGER THE BOND
name a cellular structure that is stabilized by hydrogen bonds
double strand DNA.
the bases are stabilized by H bonds
water molecules attached to polar amino acids through hydrogen bonding…….
are often available for further hydrogen bonding with small molecules
is hydrogen bonding in itself sufficient for drug-receptor interaction?
give an example
NO, but the summation of various forces of interaction may be sufficient to form a stable drug-receptor complex.
for example, epinephrine requires 3 bonds (one of them being a hydrogen bond) to bind to its receptor. requires hydrogen bond, van der waals/hydrophobic interaction, and upon protonation, the aliphatic amine will form an ionic bond with the receptor
what are the weakest, but most ubiquitous interaction between molecules?
van der waals forces
why do van der waals’ forces arise?
when are they exerted?
arises due to the polarizability of molecules
exerted when 2 uncharged atoms approach very closely and the electrons in one atom are attracted to the protons in the nucleus of the other atom
“van der waals radar”
you need to have proper distance between the atoms for an interaction.
at long distances they are attractive with maximum binding when the atoms are separated by the sum of their van der waals radii.
if they approach more closely, attractive forces disappear and strong repulsion occurs
very tricky to have a proper interaction
true or false
although van der waals forces are weak, the summation of forces in large molecules can be significant
true
although van der waals forces are weak, the summation of forces in _____ molecules can be significant.
explain
in LARGE molecules
ex: an aromatic ring can contribute to binding energy (3-6kcal/mol)
if the ligand’s shape is highly complementary to a cleft in the receptor and fits tightly, van der waals interactiosn can contribute to high binding energies
such is the case with benzodiazepines (7 membered ring) which is complementary to a FLAT aromatic ring such as benzene
define a hydrophobic interaction
association of a relatively nonpolar molecule/group in an aqueous medium with other nonpolar molecules
true or false
hydrophobic interactions are relatively weak
true
they are weak individually, but can be useful in drug-receptor interactions if other interactions are present (as in the case of epinephrine binding to its receptor)
