Chemical Basis for Drug Action

drug

a chemical substance of known structure, other than an essential dietary ingredient, which, administered to a living organism, produces a biological effect

organic

drugs are usually _____ compounds

drug target

a molecule in the body that is intrinsically associated with a particular disease process and that could be addressed by a drug to produce a desired therapeutic effect

proteins (enzyme, receptor, channel) and nucleic acids (DNA or RNA)

drug targets are usually _____

paul ehrlich

who said the famous quote: “the drug will not work unless it is bound”

drug-target complex

a drug binds to its target to form a _____

conformation

the drug-target complex changes the _____ of the target

drug and a free target

the drug-target complex has a lower energy than the sum of a _____

covalent and non-covalent

what are the 2 types of forces used to bond molecules?

alkylation, acylation, phosphorylation, and rearrangement

what are the examples of covalent bonds?

ionic bonds (electrostatic interactions), dipole interactions, van der walls’ interactions, and additional aromatic interactions

what are the examples of non-covalent bonds?

chemical

covalent bonds are a type of _____ reaction

molecular

non-covalent bonds are a type of _____ interaction

covalent bond

a chemical bond that involves the sharing of electron pairs between atoms

octet rule

states that all atoms in a molecule are required to have 8 valence electrons to become stable

tetrahedron: attached to 4 things with single bonds

what geometric form does an sp³ C take?

trigonal planar: one double bond and 2 single bonds

what geometric form does an sp² C take?

linear: one triple bond and one single bond

what geometric form does an sp C take?

covalent

only a small number of drugs act by forming _____ bonds with their biological target

reversed

covalent bonds cannot be _____

the duration of action may be too long, the specificity of the drug may be low → prolonged adverse effects, high reactivity

what are the problems that come with creating a covalent bond?

acylation

a type of covalent bond where a drug add an alkyl group (C_nH_2n+1-) to its target

cancer

alkylation is used in _____ treatment

nitrogen mustards

1st alykylating agents used medically, as well as the 1st modern cancer chemotherapies

alkylation

what covalent process is this image an example of?

acylation

a type of covalent bond where a drug adds an acyl group (RCO-) to its target. the drug molecules contains an ester, lactone, amide, and carbamate and the target molecule presents a nucleophilic atom (N, S, O)

beta lactam antibiotics (penicillins, cephalosporins)

what type of medication uses acylation?

acylation

what covalent process is this image an example of?

acetylcholinesterase

an enzyme that catalyzes the hydrolysis of acetylcholine

acetylcholinesterase inhibitors

what is this image showing?

phosphorylation

a type of covalent bond in which a drug adds a phosphate group to its target

organophosphates

phosphorylation uses _____ to attach to esteric site

irreversible and very toxic

phoasphorylate acetylcholinsterase is _____

phosphorylation

which covalent group creates products that are used primarily as insecticides?

rearrangement reactions

a type of covalent bond that usually occurs during when the drug is metabolized

rearrangement reactions

what covalent process is this image an example of?

non-covalent bonds

what type of bond makes up 93% of bonds?

weak

the bond energy of covalent bonds is _____

distance

the strength of a non-covalent bond is inversely proportional to the _____ between the functional group on the drug and a complementary functional group on the biological target

ionic bonds (electrostatic interactions)

bond that occurs between ionized acidic and basic functional groups or ionized acidic (-) and quaternary ammonium (+) functional groups

ionic bonds

which non-covalent bonds are the strongest?

an acid exists in the form of A^-

pKa < pH means:

[A^-] (conjugate base)

if pKa < pH then an acid exists in the form of:

[HA] (acid)

if pKa > pH then an acid exists in the form of:

pKa - pH = log₁₀[HA]/[A^-]

what is the equation used to figure out the concentration of acid or conjugate base?

[BH]⁺ (conjugate acid)

if pKa > pH, then a base exists in the form of _____

[B] (base)

if pKa < pH, a base exists in the form of _____

pKa - pH = log₁₀[BH]⁺/[B]

what is the equation used to figure out the concentration of base or conjugate acid?

dipole interactions

a type of covalent interaction in which electronegativity drives the bond between atoms

electronegativity

a chemical property that defines the tendency of an atom to attract a shared pair of electrons towards itself

dipoles

term that refers to the separation of positive charge and negative charge within a system

the bigger the dipole moment

the greater the difference of electronegativity values of the atoms, _____

F, O, Cl, N, Br

rank the following from most electronegative to least: Cl, N, Br, O, F

ion-dipole (full charge ion)

_____ have higher energy than dipole-dipole interactions

hydrogen bond

a special dipole-dipole interaction between a partially positively charged hydrogen atom attached to a highly electronegative atom (F, O, N), and another partially negatively charged atom (F, O, N)

strongly electronegative (F, O, N) and posses a localized lone pair of electrons

hydrogen bond acceptors usually are:

strongly electronegative atoms with a hydrogen atom attached

hydrogen bond donors usually are:

van der waals’ interactions

a non-covalent interaction between any atoms or molecules caused by temporary dipoles due to uneven or unsymmetrical electronic distribution, or induced dipole

weak

are van der waals’ interactions strong or weak?

aromatic interactions

occur when aromatic rings stack (one from drug, one from target)

cation-aromatic ring interactions

occurs when a cation (positive ion) from a drug molecule binds to an aromatic group from the target protein

chelation

a type of bonding of ions and molecules to metal ions (metal ion binds to ligand at 2 or more points)

calcium

what compound can cause issues with medications that use chelation?

covalent bonding, electrostatic interactions, hydrogen bonding, dipole-dipole interactions, and van der waal’s interactions

rank the following bonds/interactions in order of strength: hydrogen bonding, covalent bonding, dipole-dipole interactions, electrostatic interactions, and van der waals’ interactions

target

a drug must bind to its _____ to produce a therapeutic effect

covalent

only a small number of drugs act by forming _____ bonds with their biological target

non-covalent

most drugs bind to their targets using _____ bonds

distance

the strength of a non-covalent bond is inversely proportional to the _____ between the functional group on the drug and a complementary functional group on the biological target

covalent, non-covalent

bond energy = _____ > _____