• Electronegativity, charge distribution, and molecular bonding structure
• Demonstrate an understanding of electronegativity; understand and be able to clearly explain the basis for electronegativity trends in terms of fundamental laws of electrostatic interactions (Coulomb’s Law).
• Understand how to use relative electronegativities of atoms to clearly depict charge distribution across chemical bonds.  Be able to quickly predict partial charges on atoms within given molecules.
• Draw molecular structures showing all bonds from a given molecular representation
• Noncovalent interactions and intermolecular forces
• Understand and be able to clearly discuss and diagram the basis for attractions between molecules/ions to include ion hydration, hydrogen bonding, London dispersion, dipole-dipole, ion-dipole, and cation-p electron  interactions.
• Understand and use the relative magnitude (in kJ/mole) of chemical bonds (e.g. ionic, covalent and metallic) vs intermolecular forces (hydrogen bonding, London dispersion, dipole/dipole) interactions.
• Quickly draw diagrams that clearly show appropriate partial charges and intermolecular interactions among a given set of molecules or ions.
• Predict points of potential H-bond donors and acceptors for any given molecular structure.
• Predict and discuss relative boiling points (also vapor pressure, melting points, viscosity, surface tension) from molecular structure
• Solubility and hydrophilic/hydrophobic substances
• Understand the difference and be able to predict relative polarities and solubilities (hydrophilic/hydrophobic, lipophilic/lipophobic) of a given molecular structure
• Understand and clearly explain the basis for the structure of surfactants and soap molecules
• Understand and describe the basis for micelle formation and action
• Understand what is meant by the octanol-water partition coefficient and clearly describe its significance (P and log P)
• Distribution of molecular kinetic energies
• Calculate fractions of molecules having kinetic energies greater than a given energy at a given temperature
• Graphically represent and be able to clearly explain the distribution of kinetic energies of a collection of molecules at various temperatures
• Understand kinetic energy conversion into potential energy to separate molecules, to break bonds, or to react molecules

• Molecular structure
• Quickly draw Lewis structures for a given molecule or ion
• Predict electron arrangement, molecular geometry, hybridization, and bond angles around given atoms in molecules
• Multiple bond structure
• Outline, discuss, and use aromatic electronic structure and geometry
• Know and discuss double/triple bond geometry and hybridization
• Outline and diagram cis/trans geometry about carbon-carbon double bonds
• Molecules: carboxylic acids, fatty acids, amino acids, and alkaloids
• Outline the structure of a carboxylic acid functional group and diagram its acid/conjugate base forms
• Be able to draw the structure for fatty acids, to include those having one or more points of unsaturation
• Draw the general structure for amino acids and be able to clearly diagram the acid/conjugate base forms for both the carboxylic acid and the amine functionalities
• Know what an alkaloid is and be able to quickly draw acid/conjugate forms of a given alkaloid.

• Condensation reactions
• Use partial charges within molecules to outline the basic mechanism for condensation reactions
• Predict and outline fundamental mechanisms for condensation reactions between
• Acids and alcohols
• Phosphates and alcohols
• Amino acids
• Carbohydrates
• Nucleotides
• Esters
• Hydrolysis reactions
• Understand hydrolysis reactions under acidic and basic conditions
• Outline peptide hydrolysis chemical equations
• Understand fat hydrolysis (e.g. formation of surfactant—soap--from animal fat and lye)

• Phospholipids
• Understand the component substructures within phospholipid molecules
• Know the molecular structures of the alcohols (glycerol, serine, choline, ethanolamine) used to make phospholipids
• Outline the chemical reactions and mechanisms for the formation of phospholipids from molecular subcomponents
• Outline the reactions involved in phospholipid hydrolysis
• Fats, oils, and fatty acids
• Know the structure of saturated, monounsaturated, polyunsaturated, and trans fats; describe associated health effects
• Understand cis- and trans-geometry and the formation of trans-fats
• Relate the melting points of fats and oils to molecular structure
• Understand olestra’s synthesis, structure, utility, and limitations
• Membranes
• Understand and draw the molecular structure of membranes
• Understand and describe the forces that hold membranes together
• Clearly outline the role of cholesterol in cell membranes
• Predict relative membrane permeability for a variety of types of molecules or ions

• Amino acids
• Know the general molecular structure of amino acids
• Be able to quickly draw the complete molecular structure showing all bonds for all of the following amino acids:
• AA's with nonpolar side chains [Alanine(Ala,A), Valine(Val,V), Leucine(Leu,L), Isoleucine(Ile,I), Phenylalanine(Phe,F)]
• AA's with polar uncharged side chains [Glycine(Gly,G), Serine(Ser,S), Threonine(Thr,T), Tyrosine(Tyr,Y), Cysteine(Cys,C), Asparagine(Asn,N), Glutamine(Gln,Q)]
• AA's with carboxylic acid side chains [Aspartic Acid(Asp,D), Glutamic Acid(Glu,E)]
• AA's with basic side chains [Lysine(Lys,K), Arginine(Arg,R), Histidine(His,H)]
• Acid-base systems
• Predict reactions of acids with water; predict reaction of bases with water.
• Write and use equilibria expressions for dissociation of weak acids and bases, K_a and K_b; pKa’s
• Know the Henderson-Hasselbalch equation: be able to understand and use.
• Predict predominant (and relative amounts) of acid/base forms (e.g. COOH/COO^-,  –NH₃⁺/-NH₂ ) present at a given pH.
• Acid-base properties of amino acids
• Predict acid-base forms of amino acids present at various pH’s
• Relate pH to amino acid functional group solubility in lipids or water
• Understand what isoelectric points (pI) are and how to determine them from the pK_a's of amino acids

• Understand how peptide bonds are formed and draw appropriate resonance structure to explain peptide bond geometry
• Know the primary structure of peptides
• Understand protein secondary structure; draw diagrams to represent the underlying reason for the formation of alpha helices and beta sheets
• Understand the various types of interactions that can occur between side chains; draw appropriate diagrams and clearly discuss these
• Understand protein tertiary and quaternary structures
• Understand the underlying reasons for the structure of globular proteins
• Clearly discuss and diagram prions formation process and their relevance
• Outline major functions of proteins in the human body

• Understand the two fundamental requirements for a chemical reaction to occur…
• Draw reaction coordinate-energy profiles and clearly label activation energies, and heat gained or lost
• Understand and be able to clearly explain the role of catalysts
• Understand and be able to use fundamental principles to clearly describe the dependence of reaction rate changes with temperature
• Demonstrated the ability to calculate relative rates of reactions for different activation energies or temperatures
• Know and be able to use the Arrehenius equation for rate constant determination
• Understand relative impacts of temperature changes on rates for chemical reactions with low and high activation energies

• Chemical kinetics
• Understand what is meant by the rate law and outline the experimental procedures and methodology to determine reaction order
• Use a given rate law to calculate rate constants and their associated units
• Understand how to experimentally determine a reaction's activation energy using Arrhenius plots
• Be able to use activiation energies to predict rate constants at different temperatures
• Understand the effect of activation energy on the degree of rate constant changes with temperature
• Michaelis-Menton kinetics
• Write equilibria associated with enzyme-substrate interactions
• Understand how reaction order changes with substrate concentration
• Be able to use the Lineweaver-Burke relationship to calculate V_max, turnover number, and K_M
• Understand the significance of K_M; understand the relation of K_M to enzyme-substrate complex stability and to maximum reaction rate
• Enzyme-substrate interactions
• Be able to draw and to clearly explain reaction energy diagrams for enzyme-substrate interactions
• Understand the effects of inhibitors and what is specifically meant by IC50
• Understand and clearly explain the basis for important types of noncovalent enzyme-substrate interactions
• Clearly describe the enzyme inhibition process

• Introduction to pharmacology
• Understand the drug approval process
• Understand the three nomenclature systems (chemical name, generic name, trade name) used to identify a particular therapeutic substance
• Drug-receptor binding
• Understand and clearly discuss the ligand-receptor interactions; know the underlying physical principles that govern these interactions
• Understand chirality, enantiomers, racemic mixtures, and the chiral specificity of many drug receptors
• Receptors
• Understand the various types of drug receptors present within the human body
• Understand the various types of receptor responses
• Understand receptor response differences to agonists and antagonists
• Quantifying effects of drugs on the human body
• Describe and plot drug concentration/dose vs response curves; understand what is meant by EC50, IC50, and LD50
• Understand and compare the relative potency and efficacy for two or more drugs; draw or interpret dose-response graphs that illustrate these
• Understand and clearly discuss the linkage between therapeutic and toxic doses

• Absorption of drugs
• Understand routes of drug administration
• Relate lipophilic/lipophobic and other drug properties to effectiveness of absorption
• Distribution of drugs
• Understand mechanisms of drug distribution
• Relate lipophilic/lipophobic and other drug properties to effectiveness of distribution
• Elimination of drugs
• Understand excretion processes the drug properties that affect these
• Understand drug metabolism and the drug properties that affect these

• Understand the inflammation mechanism of action initiated by arachidonic acid (phospholipid release of arachidonic acid, generation of prostaglandins and thromboxanes through cyclooxygenase pathway, generation of leukotrienes through lipoxygenase mechanism)
• Understand the mechanism of action of cyclooxygenase (COX) inhibitors
• Identify key structural features of NSAIDs and understand of specific important interactions with COX enzymes
• Understand the specific interaction between the NSAID carboxylic group  and the COX Arg-120 side chain; describe and effectively explain the effect upon K_m values that occur when neutral glutamine is substituted for Arg-120
• Understand and clearly discuss aspirin's unique mechanism of action for irreversible COX inhibition

• Understand key differences between COX-1 and COX-2 enzymes, their physiological roles, and their respective inhibitors
• Clearly describe the rationale for the development of COX-2 inhibitors
• Explain the structure differences between nonspecific COX inhibitors and COX-2 specific inhibitors; relate these differences to active site geometries of thee two enzymes
• Use COX-1 and COX-2 IC50 values for various substances to evaluate their respective potential for therapeutic development

Lsn 14: Central Dogma and Complex Ions

• Complex ions
• 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.
• Outline the mechanism of action for platinum compounds [e.g. cisplatin PtCl₂(NH₃)₂] as chemotherapeutic agents for cancer patients
• Nucleic acid structure
• Understand the structure of DNA and RNA to include the major components and specific features
• Understand the condensation mechanism of action to form phosphate diester polynucleotides
• Clearly explain the underlying physical basis for the attractions between the two strands of double helix DNA
• Central dogma
• Understand and clearly describe how genetic information is encoded in DNA
• Explain what a gene is, what it does, and the two roles of the major regions (promoter and coding) of DNA gene templates
• Generate a possible DNA sequence for the coding of a given peptide
• Interpret a DNA or RNA sequence to generate an amino acid sequence that is coded for by this

• Understand and draw the skeletal structure for steroids
• Discuss and predict the lipophilic/lipophobic properties of steroids
• Explain the effects of anabolic steroids and of each of the two classes of corticosteroids (mineralcorticoids and glucocorticoids)
• Outline where steroids are produced, what their sources are, and how they work hormones in the human body
• Discuss steroidal sex hormones

• Inflammation and steroids
• Understand the molecular basis of inflammation to include the role of phospholipases, arachidonic acid, cyclooxgenase, lipoxygenase, prostaglandins, thromboxanes, and leukotrienes
• Explain the molecular mechanism of action for steroids as anti-inflammatories
• 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
• Understand the roles of prednisone and cortisone medications respectively
• Zinc fingers
• 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 the relative intracellular and extracellular concentrations of sodium, potassium, calcium, and chloride ions
• Outline and clearly explain the steps that occur to pass a nerve impulse from one neuron to another
• Know the structure of acetylcholine and explain how it is synthesized and hydrolyzed
• Clearly explain the two major mechanisms used to reduce neurotransmitter concentration levels at nerve synapses
• Understand the two (nicotinic and muscarinic) major classes of cholinergic (acetylcholine) receptors and the mechanism of action for each

• 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.
• Explain Free Energy changes associated with ATP-ADP interconversion; discuss and effectively use the concept of coupled reaction energetics

• 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
• Demonstrate the ability to calculate Free Energy changes, equilibrium constants, and electric potentials associated with given reactions
• Explain and calculate cell membrane potentials associated with ion concentration gradients
• Relate resting membrane potential to ion permeability and to intracellular/extracellular concentrations
• Calculate Free Energy changes necessary to move substances across concentration gradients and to move ions across potential gradients

• 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

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

• Understand the mechanism of action for local anesthetics
• Relate pK_a's to local pain anesthetics
• Understand the history of cocaine use by humans
• Describe the mechanism of action for general anesthetics
• Be familiar with the molecular structures for the more widely used general anesthetics

• Relate the structure of opioid receptors to opioid ligand geometry and identify key features of each
• Understand the history of opioid use and development by humans
• Understand the side-effects of opioids
• Describe the structure of natural opioids found in the human body and be familiar with its historical discovery

• Describe the geometry of adrenergic receptors
• Classify the role of the three main types of norepinephrine receptors (alpha, beta 1, and beta 2)
• Describe the interaction of adrenergic receptors with neurotransmitters
• Discuss the mechanism of action of activated adrenergic receptors
• Be familiar with medications that target adrenergic receptors and discuss their mechanism of action

Lsn 28:  Review