IMC 01: Review of Chemistry Fundamentals

Question 1

Review Periodic Table

Answer 1

• groups
• s and p orbitals

Question 2

What is electronegativity?

Answer 2

measurement of how strongly an atom pulls on its valence electrons

• influenced by the charge of the nucleus and the size of the atom
• more protons (moving right across the periodic table) = greater pulling force on valence electrons
• less electron orbitals (moving up the periodic table) = electrons closer to nucleus experience greater pull
• adding extra orbitals (moving down the periodic table) reduces electronegativity more than moving to the left of the periodic table
• ie. O is more electronegative than Cl, and N has approximately equal electronegativity to Cl

Question 3

Electronegativity

Carbon-Carbon and Carbon-Hydrogen bonds

Answer 3

• carbon and hydrogen have nearly equal electronegativity (C = 2.55, H = 2.20)
• C-H and C-C bonds are non-polar – nearly equally dispersed electron cloud
• for most drug molecules, C-H and C-C bonds contribute to the scaffold of the drug
• hold functional groups in place for making non-covalent interactions with targets

Question 4

Electronegativity

Polar Covalent Bonds

Answer 4

• electrons are shared unevenly between covalently bonded atoms
• instills partial charges (δ+ or δ-) on bonded atoms that can change the chemical and biological properties of a drug

Question 5

What is the hybrid orbital theory?

Answer 5

empirical method that explains the shapes of molecules

• combines the valence orbitals to create degenerate (same energy) hybrid orbitals

Question 6

What does an sp hybrid orbital look like?

Answer 6

combination of s-orbital and p-orbital

Question 7

What is a sigma bond?

Answer 7

(single bond)

• hybrid orbitals + s orbitals
• hybrid orbitals + other hybrid orbitals

Question 8

What is a pi bond?

Answer 8

(double bond)

unhybridized p orbitals + other p orbitals of the same orientation

Question 9

What type of orbital is the linear shape?

Answer 9

sp hybridized

• need sigma bond
• need 2 pi bonds (need 2 p orbitals that are not hybridized)

Question 10

What type of orbital is the trigonal planar shape?

Answer 10

sp2 hybridized

• sigma bond (single bond)
• pi bond (double bond)
• cannot hybridize all 3 p orbitals with s orbital – need an unhybridized p orbital to make pi bond

Question 11

What type of orbital is the tetrahedral shape?

Answer 11

sp3 hybridized

• 4 bonds hybridizing all orbitals to make sp3

Question 12

What are the steps to explain the bonding of CH4 using hybrid orbital theory?

Answer 12

1. draw electron configurations for carbon and hydrogen
2. hybridize the valence orbitals (sp3) – 4 sigma bonds in CH4
3. fill in the electrons that each hydrogen atom contributes
4. summarize with a statement

Question 13

What is resonance?

Answer 13

a way of describing chemical bonds that are representative of several contributing structures (resonance structures)

• resonance structures are not ‘real’
• real structure is the weighted average of the resonance structures – the more ‘stable’ a resonance structure is, the more it can contribute to the ‘real’ structure
• resonance structures may impart important properties to molecules or functional groups

Question 14

What types of electron shifts can occur in resonance structures?

Answer 14

• from pi bond to adjacent bond position
• from pi bond to adjacent atom (lone pair)
• from atom (lone pair) to adjacent pi bond

Question 15

What can the stability of a resonance structure be predicted by?

Answer 15

• lack of charge separation (more neutral = better)
• electronegative atoms possess negative charge

Question 16

Which resonance structure is the major contributor to the ‘real’ structure?

Answer 16

• the resonance structure that has less charge separation (more neutral), and the more electronegative atoms possess the negative charge
• charged resonance structures have very minor contributions to the overall structure, but will impact its physicochemical properties including pKa

Question 17

What is Huckel’s rule?

Answer 17

predicts that a planar ring molecule will have aromatic properties if it has 4n + 2 pi-electrons, where n is a non-negative integer

Question 18

What are the key things that make an aromatic group?

Answer 18

• cyclic AND planar group
• each atom must have a p orbital that is perpendicular to the plane of the ring
• with 4n+2 delocalized electrons

Question 19

What are aromatic compounds stabilized by?

Answer 19

stabilized substantially by pi-electron delocalization

Question 20

What are electron-withdrawing groups?

Answer 20

pull electron density from the aromatic rings

• these groups have resonance structures that induce positive charges in the aromatic ring
• ie. NO2, CN, carbonyl, halogens
• ie. halogen atoms withdraw electron density due to their electronegativity, however they can donate their lone pairs to the ring as well – overall effect is electron withdrawing

Question 21

What are electron-donating groups?

Answer 21

push electron density into aromatic rings

Question 22

What are strong acids?

Answer 22

completely dissociate to donate proton (H+) in aqueous solution – ie. HCl

Question 23

What are strong bases?

Answer 23

completely dissociate in water to generate one or more hydroxide ion (OH-) – ie. NaOH

Question 24

What are weak acids and weak bases?

Answer 24

partly dissociate in aqueous environments

• chemistry of weak acids and bases is often exploited in drug molecules and formulations – ie. using different pH in the digestive tract to influence ionization of drugs

Question 25

What is pKa?

Answer 25

constant that is used to efficiently describe the relative acidity of an acid

Question 26

The more stable the conjugate base, _________.

Answer 26

the more acidic the compound will be

Question 27

In terms of acids and bases, what do we tend to focus on in pharmaceutical sciences?

Answer 27

physiologic pH and what functional groups may carry ionic charges under physiologic conditions

Question 28

Functional groups that have pKa transitions ±2 from the pH will be…

Answer 28

99% protonated or deprotonated

• therefore can consider these to be practically fully ionized or neutral at physiologic pH (7.4)

Question 29

What does how acidic or basic a compound or functional group is depend on?

Answer 29

depends on its chemical structure and primarily revolves around the stability of the conjugate acid or base

Question 30

Describe the protonated vs. deprotonated state when pH = pKa.

Answer 30

50/50 protonated and deprotonated

Question 31

Ionization of AH and BH+ Acids

Answer 31

(see graph)

• HA acids with low pKa values are charged at pH 7.4
• BH acids with high pKa values are charged at pH 7.4