Basics

• Understanding electronegativity and underlying basis for electronegativity trends in terms of fundamental laws of electrostatic interactions (Coulomb’s Law).
• Understanding and quickly predicting partial charges on atoms within neutral molecules.
• Drawing molecular structures showing all bonds from a given molecular representation
• Aromatic electronic structure and geometry
• Double/triple bonds and hybridization

• Relative magnitude (in kJ/mole) of chemical bonds (ionic, covalent and metallic) vs intermolecular forces (hydrogen bonding, London dispersion and dipole/dipole).
• Diagram of intermolecular interactions among molecules.
• Predicting points of potential H-bond donors and acceptors for any given molecular structure.
• Prediction of relative boiling points  (also vapor pressure, melting points, viscosity, surface tension) from molecular structure

• Polar (water soluble molecules) vs nonpolar (lipophilic molecules)
• Surfactants and soap molecules
• Octanol-water partition coefficients and significance (P and log P)

• Graphical representation and explanation of distribution
• Distribution at various temperatures
• Calculating fractions of molecules having KE greater than a given energy at a given temperature
• Understanding of KE conversion into potential energy to separate molecules, to break bonds, or to react molecules

• Two fundamental requirements for a chemical reaction to occur…
• Reaction coordinate-energy profile (activation energy, heat gained or lost)
• Role of catalysts
• Understanding dependence of reaction rate changes with temperature
• Calculating relative rates of reactions for different activation energies or temperatures
• Understanding relative impacts of temperature changes on reaction rates for chemical reactions with low and high activation energies

• Basic mechanism
• Prediction of reactions between
• Acids and alcohols
• Phosphates and alcohols
• Amino acids
• Carbohydrates
• Nucleotides
• Esters
• Hydrolysis reactions under acidic and basic conditions
• Protein hydrolysis
• Fat hydrolysis (e.g. formation of surfactant—soap--from animal fat and lye)

• Formation and structure of phospholipids (glycerol, serine, choline, ethanolamine)
• Structure of saturated, monounsaturated, polyunsaturated, and trans fats; associated health effects
• Cis- and trans-  double bond geometry; formation of trans- fats
• Relate the melting points of fats and oils to molecular structure
• Olestra’s formation, structure, utility, and limitations
• Molecular structure of membranes

• Reaction of acids with water; reaction of bases with water.
• Equilibria expressions for dissociation of weak acids and bases, K_a and K_b; pK_a’s
• Henderson-Hasselbalch equation: be able to understand and use.
• Prediction of predominant (and relative amounts) of acid/base forms (e.g. COOH/COO^-,  –NH₃⁺/-NH₂ ) present at a given pH.

• Structure
• Acid-base behavior at various pH’s
• Knowing structure of common AA’s:
• Nonpolar (glycine, alanine, valine, leucine, isoleucine, phenylalanine)
• Polar (serine, tyrosine, cysteine)
• Acidic (aspartic acid, glutamic acid)
• Basic (lysine)
• Isoelectric points (pI) of amino acids

• Peptide bonds
• Primary structure
• Secondary structure; alpha helices and beta sheets
• Interactions between side chains; tertiary and quaternary structure
• Structure of globular proteins
• Prions
• Protein functions

• Chemical Kinetics
• Rate Law
• Experimental procedure and methodology to determine reaction order
• Calculation of rate constants and understanding of associated units
• Experimental determination of activation energy, Arrhenius plots
• Prediction of rate constants at different temperatures
• Understanding of the effect of activation energy on degree of rate constant changes with temperature
• Michaelis-Menton kinetics
• Equilibria
• Reaction order as a function of substrate concentration
• Use of Lineweaver-Burke equation to calculate V_max, turnover number, and K_M
• Effect of inhibitors, IC50
• Significance of K_M; relation of K_M to enzyme-substrate complex stability and to maximum reaction rate
• Reaction energy diagrams
• Understanding of noncovalent enzyme-substrate interactions
• Enzyme inhibition

• Cyclooxygenase substrate and inflammation mechanism (e.g. phospholipid release of arachidonic acid, generation of prostaglandins and thromboxanes through cyclooxygenase pathway, of leukotrienes through lipoxygenase mechanism)
• Mechanism of Action of COX inhibitors
• Key structural features of NSAIDs and understanding of specific important interactions with COX enzymes
• Key differences between COX-1 and COX-2 enzymes and their respective inhibitors
• Rationale for the development of COX-2 inhibitors
• Understanding of resonance structures for COX - NSAIDs interaction geometry and mechanism
• Aspirin's unique mechanism of action for irreversible COX inhibition

• Understand the molecular basis of inflammation to include the role of phospholipases, arachidonic acid, cyclooxgenase, lipoxygenase, prostaglandins, thromboxanes, and leukotrienes
• Understand the emerging relevance of inflammatory processes in various diseases
• Understand the importance of C-reactive protein levels and the enzyme drug targets that pharmaceutical companies are focusing on
• Explain the molecular mechanism of action for steroids as anti-inflammatories
• Explain the effects of anabolic steroids and of each of the two classes of corticosteroids (mineralcorticoids and glucocorticoids)
• Understand the roles of prednisone and cortisone medications respectively

• Understand the structure of DNA and RNA to include the major components and specific features; know how polynucleotides are synthesized and hydrolyzed
• Clearly explain the underlying physical basis for the attractions between the two strands of double helix DNA
• Understand the central dogma
• Explain what a gene is, what it does, and the two roles of the major regions (promoter and coding) of DNA gene templates

• Understand the structure of complex ions and be able to explain the basis for their interaction
• Relate Lewis acid/base chemistry to complex ion components
• Clearly explain why complexes are colored and demonstrate an understanding of relevant molecular orbital energies
• Show how transition metal ion valence electron energy levels shift as ions are introduced into octahedral and tetrahedral ligand environments; understand and be able to clearly explain the basis for these shifts
• Understand and diagram the structure of important biochemical complexes to include iron in hemoglobin, magnesium in chlorophyl and cobalt in B-12.
• Diagram and effectively discuss the structure of zinc fingers; clearly show the amino acid residues that interact with the zinc ion and how zinc fingers affect protein shape
• Explain the underlying basis for the zinc finger mechanism of action in steroidal interactions with DNA
• Discuss a new area of drug research that targets the zinc fingers in estrogen receptors to treat breast cancer

• Understand and be able to use the Second Law of Thermodynamics to predict reaction spontaneity
• Clearly explain how spontaneity is related to Free Energy change.
• Calculate Free Energy changes necessary to move substances across concentration gradients and to move ions across potential gradients
• Demonstrate the ability to calculate Free Energy changes, equilibrium constants, and electric potentials associated with given reactions
• Use tables of reduction potentials to predict reaction spontaneity
• Be able to relate concentrations to associated electric potentials (e.g. Nernst Equation) and changes in Free Energy
• Explain Free Energy changes associated with ATP-ADP interconversion; discuss and effectively use the concept of coupled reaction energetics
• Understand the sodium-potassium pump mechanism to maintain ion concentration gradients and the array of energetics associated with this
• Understand the role of oxidative phosphorylation as the major energetic source to generate ATP; outline the specific redox reaction that is coupled to ATP production

• Understand the relative intracellular and extracellular concentrations of sodium, potassium, calcium, and chloride ions
• Explain and calculate cell membrane potentials associated with ion concentration gradients
• Relate resting membrane potential to ion permeability and to intracellular/extracellular concentrations
• Describe the structure of voltage gated sodium ion channels and potassium ion channels to explain how they work.  Understand the role of these ion channels in moving nerve pulses down an axon
• Outline and clearly explain the steps that occur to pass a nerve impulse from one neuron to another
• Understand the two (nicotinic and muscarinic) major classes of cholinergic (acetylcholine) receptors and the mechanism of action for each
• Understand the role and the basic general mechanism of G-Protein Coupled Receptors (GPCR) in cell signaling processes; explain the importance of these receptors in the pharmaceutical industry
• Clearly explain the two major mechanisms used to reduce neurotransmitter concentration levels at nerve synapses
• Know the structure of acetylcholine and explain how it is synthesized and hydrolyzed

• Describe what an ion channel is and the specific properties of the substance that forms the channel
• Understand and be able to clearly explain the physical basis for the selectivity of sodium and potassium ion channels
• Outline the difference and define what is meant by voltage-gated and ligand-gated ion channels
• Understand how increased permeability can affect voltage-gated ion channels

• Know the molecular structures for these neurotransmitters:
• Cathecholamines: L-Dopa, dopamine, norepinephrine, and epinephrine
• Amino Acids: Glutamate, Aspartate, Glycine, GABA (gamma-aminobutyric acid)
• Understand the role of glycine and GABA receptors
• Be able to explain the electrochemical basis for their inhibitory effects
• Clearly explain how each of the following substances affects the GABA-ergic system: ethanol, barbiturates, strychnine, diazepam (valium), and caffeine
• Understand how PCP (angel dust) and Memantine (Namenda) affect the glutamate receptor NMDA (N-Methyl-D-Aspartate)
• Understand the synthesis steps involved in the production of L-DOPA, dopamine, norepinephrine, and epinephrine
• Explain the role of monoamine oxidase (MAO) for catecholamine neurotransmitters; identify the role of MAO inhibitors.
• Explain the effect of dopamine levels on brain activity
• Explain the effects of cocaine and of amphetamines on the dopamin-ergic system
• Outline the role of seratonin and identify the substance from which it is produced
• Explain what SSRI's are and what they are used for
• Classify the role of the three main types of norepinephrine receptors (alpha, beta 1, and beta 2)