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)
can tyrosine form a hydrophobic interaction?
YES (has aromatic ring)
but also has additional OH group so can form an additional interaction
what is a benzyl group?
benzene ring with CH2 and another substituent
can a benzyl group form a hydrophobic interaction
yes
can an isopropyl group form a hydrophobic interaction
yes
give 2 examples of drugs that only use non ionic forces to form a drug-receptor interaction
captopril and trimethoprim
explain how hydrophobic forces together can aid in drug-receptor interaction
the addition of 1 oil droplet to water will form a small ball of oil that doesnt interact with water.
however, with the addition of the 2nd droplet, energy is gained and the replusive forces are more difficult to keep away from each other. energy has been gained from the addition of the 2nd droplet
what is the target of captopril?
ACE (angiotensin converting enzyme)
what is the target of trimethoprim?
inhibits bacterial dihydrofolate reductase.
used in combination with sulfa drugs
is bacterial dihydrofolate reductase found in humans?
target of trimethoprim
YES. therefore, the functional groups need to be correctly positioned and highly selective to bacterial folate reductase to avoid interaction with the human enzyme
how many drug-receptor interactions are necessary for captopril to bind to ACE
5
what will happen when a secondary aliphatic amine gets protonated?
it will gain a positive charge and better interact with water
true or false
carboxamide is acidic
false – it’s neutral
for parenteral injections, you must have good ___ solubility
water
why is an advantage of weakly acidic drug formulation?
the salts of weak acids and bases are soluble in water.
ex: benzoic acid and sodium hydroxide together will produce benzoate salt which is very soluble in water. neutralization reaction
