IMC 01: Review of Chemistry Fundamentals Flashcards
Review Periodic Table
- groups
- s and p orbitals
What is electronegativity?
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
Electronegativity
Carbon-Carbon and Carbon-Hydrogen bonds
- 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
Electronegativity
Polar Covalent Bonds
- 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
What is the hybrid orbital theory?
empirical method that explains the shapes of molecules
- combines the valence orbitals to create degenerate (same energy) hybrid orbitals
What does an sp hybrid orbital look like?
combination of s-orbital and p-orbital
What is a sigma bond?
(single bond)
- hybrid orbitals + s orbitals
- hybrid orbitals + other hybrid orbitals
What is a pi bond?
(double bond)
unhybridized p orbitals + other p orbitals of the same orientation
What type of orbital is the linear shape?
sp hybridized
- need sigma bond
- need 2 pi bonds (need 2 p orbitals that are not hybridized)
What type of orbital is the trigonal planar shape?
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
What type of orbital is the tetrahedral shape?
sp3 hybridized
- 4 bonds hybridizing all orbitals to make sp3
What are the steps to explain the bonding of CH4 using hybrid orbital theory?
- draw electron configurations for carbon and hydrogen
- hybridize the valence orbitals (sp3) – 4 sigma bonds in CH4
- fill in the electrons that each hydrogen atom contributes
- summarize with a statement
What is resonance?
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
What types of electron shifts can occur in resonance structures?
- from pi bond to adjacent bond position
- from pi bond to adjacent atom (lone pair)
- from atom (lone pair) to adjacent pi bond
What can the stability of a resonance structure be predicted by?
- lack of charge separation (more neutral = better)
- electronegative atoms possess negative charge
Which resonance structure is the major contributor to the ‘real’ structure?
- 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
What is Huckel’s rule?
predicts that a planar ring molecule will have aromatic properties if it has 4n + 2 pi-electrons, where n is a non-negative integer
What are the key things that make an aromatic group?
- 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
What are aromatic compounds stabilized by?
stabilized substantially by pi-electron delocalization
What are electron-withdrawing groups?
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
What are electron-donating groups?
push electron density into aromatic rings
What are strong acids?
completely dissociate to donate proton (H+) in aqueous solution – ie. HCl
What are strong bases?
completely dissociate in water to generate one or more hydroxide ion (OH-) – ie. NaOH
What are weak acids and weak bases?
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
What is pKa?
constant that is used to efficiently describe the relative acidity of an acid
The more stable the conjugate base, _________.
the more acidic the compound will be
In terms of acids and bases, what do we tend to focus on in pharmaceutical sciences?
physiologic pH and what functional groups may carry ionic charges under physiologic conditions
Functional groups that have pKa transitions ±2 from the pH will be…
99% protonated or deprotonated
- therefore can consider these to be practically fully ionized or neutral at physiologic pH (7.4)
What does how acidic or basic a compound or functional group is depend on?
depends on its chemical structure and primarily revolves around the stability of the conjugate acid or base
Describe the protonated vs. deprotonated state when pH = pKa.
50/50 protonated and deprotonated
Ionization of AH and BH+ Acids
(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
