Structural Properties Lecture

Question 1

Define Medicinal Chemistry

Answer 1

Intersection of synthetic organic chemistry, pharmacology and other biological specialties involved with the design of pharmaceutical agents

Question 2

What does medicinal chemistry involve?

Answer 2

Synthesis
Structure-Activity Relationships
Receptor interactions
Absorption, distribution, metabolism, and excretion (ADME)

Question 3

Who is Paul Ehrlich?

Answer 3

Grandfather of Modern medicinal chemistry
Discovered Arsphenamine (Salvarsan) (syphilis drug)
Coined “magic bullet”
Receptor binding

Question 4

Define pharmacodynamic agents

Answer 4

Drugs that act on the physiological functions of the body (analgesics, hypnotics, anti-inflammatories)

Question 5

Define chemotherapeutic agents

Answer 5

Drugs that combat pathogens and disease (antibiotics, anticancers)

Question 6

Define intermolecular binding

Answer 6

Drugs interact with receptor binding sites by forming intermolecular bonds

• Weaker than covalent bonds holding the drug together
• Can be formed and broken

Question 7

Define ionic (electrosatic) bonds

Answer 7

Oppositely charged functional groups attract
Strongest type of intermolecular bond
- Strength is inversely proportional to the distance between the two charged species
- Stronger in hydrophobic environments

Question 8

Define hydrogen bonds

Answer 8

Hydrogen’s that participate in hydrogen bonding are directly attached to a highly electronegative atom causing the hydrogen to become relatively positively charged

• The slight positive charge is strongly attracted to the lone pair so much so that it is in the beginning stages of forming a covalent bond but the charge density is not sufficient
• Distance and angle determine strength

Question 9

Key factors about fluorine

Answer 9

Most electronegative element
Useful in metabolic site blocking and comparative size to hydrogen
Sometimes it is a HBA and sometimes not

Question 10

Aromatics in hydrogen bonding

Answer 10

Aromatic rings have a defuse cloud of circulating electrons that has an overall negative charge so it can act as a hydrogen bond acceptor region (but are weak acceptors)

Question 11

Define Pi Pi stacking

Answer 11

Wake form of bonding existing between aromatic moieties when aligned in a parallel orientation

• Multiple can be incredible strong
• Usually between aromatic amino acid side chains (Tyr, Phe) that are positioned to interact with drug molecule aromatic moieties in the active site

Question 12

Define solvation

Answer 12

Like dissolves like

- Ionized compounds are more soluble in water because they form hydrogen bonds

Question 13

Define unionized compounds

Answer 13

Hydrophobic and lipophilic
Do not form strong hydrogen bonds
- Includes hydrocarbon chains and phenyl rings

Question 14

Define van der Waals interactions

Answer 14

“London forces”

• Very weak
• Areas of hydrophobicity do not possess an even distribution of non-polar areas
• Dipole interactions

Question 15

Define dipole-dipole interactions

Answer 15

Differing electronegativities of atoms comprising both the drug molecule and the binding site lead to the generation of a permanent dipole
- Interact as they come in close proximity aligning the drug so the dipoles are opposite causing a positive binding effect
(opposite directions = repulsion)

Question 16

Define ion-dipole interactions

Answer 16

A charged ionic group in one molecule interacts with the oppositely charged dipole in another molecule
- Stronger than dipole-dipole and can handle a longer distance

Question 17

Define repulsion

Answer 17

Molecules come within two close proximity their orbitals begin to overlap as do charged functional and they push apart

Question 18

Water as a solvent?

Answer 18

Solvates our proteins and receptors and drug molecules

Removal is necessary for intermolecular interactions to occur

Question 19

Define hydrophobic interactions

Answer 19

Structural regions cannot be solvated by water
Water molecules form stronger interactions and achieve greater entropy as it is lost during water removal there is a net gain in energy
- Small but over a large area can be substantial