Section 10/5/06. Junaid Malek, M.D.

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1 Section 10/5/06 Junaid Malek, M.D.

2 Equilibrium Occurs when two interconverting states are stable This is represented using stacked arrows: State A State B, where State A and State B can represent any number of separate entities Important to note that equilibrium means stable rates of interconversion, NOT equal amounts of starting and finishing product

3 Equilibrium Constant To describe relative concentrations of two states in equilibrium, we use the equilibrium constant, Keq Brackets indicate concentration expressed as moles/liter If Keq>1, equilibrium favors states to the right of the arrows If Keq<1, equilibrium favors states to the left of the arrows

4 Acidity and pka One specific type of equilibrium encountered in chemistry is that of acids in aqueous solution Acids give up protons; an acid that has given up a proton is said to be deprotonated General formula: H-A A - + H + Note that H + and proton are used interchangeably A - is referred to as the conjugate base The right side of the arrow represents the de-protonated state, while the left side represents the protonated state

5 Acidity and pka As the molecules of life exist in an aqueous environment, we can describe the equilibrium between protonated and deprotonated states as: A-H + H2O A - + H3O + Keq=[A - ][H3O + ]/[A-H][H2O]

6 Acidity and pka Since the equilibrium exists in water, there are many more molecules of water than acid As [H2O] is very large and doesn t change, we can simplify our Ka as: Ka =[A - ][H3O + ]/[A-H] Like Keq, Ka indicates which side of the equation equilibrium favors The larger the Ka, the more likely that the acid will be in a deprotonated state (and hence the stronger the acid)

7 Acidity and pka Since Ka can be very large or very small, it is easier to work on a logarithmic scale Therefore, we use pka, which is defined as pka =-log(ka ) Thus, the stronger the acid, the lower the pka When Ka changes by one order of magnitue, pka changes by one unit

8 Acidity and pka Key Concept: the stronger the acid, the more stable its conjugate base When put into water, stronger acids transfer more protons to water ph=-log[h3o + ] The lower the ph, the higher the proton concentration and the stronger the acid

9 Henderson-Hasselbalch Equation ph and pka are related via the Henderson-Hasselbalch equation: pka = ph + log([a-h]/[a - ]) How is this derived?

10 Henderson-Hasselbalch Equation: The Derivation First consider the acid dissociation constant: This equation can be rearranged to isolate the hydrogen ion concentration on the left. The new equation can be written: By definition, log 1/[H3O + ]=ph, and log 1/Ka = pka. Therefore, we can rewrite the equation to read:

11 Henderson-Hasselbach Equation If you put an acid into a solution where there is a higher concentration of protons, you protonate more molecules of acid If you put an acid into a solution where there is a lower concentration of protons, more molecules of acid will release their protons to water molecules Remember that pka is a value inherent to a particular acid pka of an acid does not change, regardless of the ph of the solution you put it into

12 Henderson-Hasselbalch Equation pka describes the equilibrium between A-H, A - and H3 + If you change any of these concentrations, you must compensate by changing the other two in order to maintain equilibrium Changing the ph changes the [H3O + ] To maintain equilibrium the values for [A-H] and [A - ] must change to compensate

13 Problem #1: Salicylic Acid O pka = 13.4 OH O O O OH pka = 3.0 OH Salicylic acid Aspirin (acetylsalicylic acid) What is the dominant species at ph=1? OH O What is the dominant species at ph=4? OH OH O What is the dominant species at ph=7? O OH O What is the dominant species at ph=14? O O O O

14 Problem #2: Saccharin Saccharin O O S N H O O S N + H + O O A B Write out the formula for Keq Keq=[B][H + ]/[A]

15 Problem #2: Saccharin The pka for saccharin = ~2(!) What is the ratio of protonated to deprotonated saccharin in each of the following solutions? Diet Soda (ph=3) 1:10 Gastric Juices (ph=1) 10:1 Human Blood (ph~7) 1:100,000

16 Acidity Trends and Resonance Strength of acid related to stability of conjugate base What contributes to stability of conjugate base? Electronegativity - stable conjugate bases have negative charge borne by electronegative atom Resonance!

17 Resonance Refers to de-localization of electrons throughout several electron orbitals in a molecule This has a stabilizing effect on molecule by distributing negative charge to several atoms O O - Remember that in reality acetate exists as neither one of these states exist but rather an average of the two O - O The negative charge is split amongst two oxygen atoms, so each bears a partially negative charge The double-bond is also shared between oxygen atoms, resulting in a 1.5 bond

18 Acidity: One Final Consideration Local environment can affect acidity For example, a positively-charged binding pocket of a protein can stabilize a negatively-charged conjugate base by forming electrostatic interactions protein O R O -

19 Problem #3: Acidity Which is the stronger acid? CH3COOH CH3CH2OH Which is the stronger acid? CH3COOH CCl3COOH

20 Central Dogma DNA RNA Protein

21 DNA and RNA: Structre DNA and RNA are polymers whose monomers are called nucleotides Each nucleotide consists of a sugar, a phosphate and a base In DNA, sugar is deoxyribose Asymmetry enforces the antiparallel directionality Chirality defines handedness of the helix

22 DNA and RNA: Structre In RNA, the sugar is ribose The extra -OH group is thought to contribute to its instability as compared to DNA The phosphate group of DNA and RNA is negatively charged at neutral ph This negative charge helps to prevent hydrolysis by repelling lone pairs from oxygen atom in water

23 Base Pairing Bases of nucleic acids responsible for storing information Sequence of base pairs encodes this information In DNA, bases on opposite strands of the helix pair with complementary bases through hydrogen bonds A pairs with T, and C with G

24 Function DNA Information storage RNA Information transfer, etc. Sugar Deoxyribose Ribose Phosphate Yes Yes Bases A,T,C,G A,U,C,G Macromolecular Structure Double stranded helix Single strand, many structures

25 Entropy and the 2nd Law of Thermodynamics Equilibria favor lower energy states What does that mean? Don t need to know exact mathematical formula, but know that energy has two components: energy associated with bonding interactions and energy associated with disorder

26 Entropy and the 2nd Law of Thermodynamics Bonding interactions are energetically favorable More or stronger bonding interactions are energetically favorable (hence at a lower energy state) Energy associated with disorder is called Entropy Measure of the disorder of a system The higher the disorder, the greater the entropy

27 Entropy and the 2nd Law of Thermodynamics Key concept: It takes energy to keep components of a system in order Thus, increasing the amount of disorder decreases the amount of energy required to maintain the state The 2 nd Law of Thermodynamics states that systems tend to more towards states of higher entropy

28 Entropy and the 2nd Law of Thermodynamics Bond energy and entropy define the energy of a state in a complex fashion Often, these to components will favor opposite sides You may not be able to figure out which component wins, but you should be able to appreciate the effects of each individually

29 DNA Hybridization The pairing of complementary single strands of DNA (hybridization) is highly favorable energetically Why? Hydrophobic effect Hydrogen bonding between complementary base pairs (also helps ensure correct base pair matching)

30 DNA Replication Proceeds in semiconservative manner

31 DNA Replication Requires 4 main components A template A primer dntp s DNA polymerase

32 DNA Replication First step is hybridization of primer to the DNA template Next, DNA polymerase binds to the DNA-primer duplex at the 3 end of the primer Then, a dntp must position itself at the 3 end of the primer and form a Watson-Crick pair with the opposite base pair on the template

33 DNA Replication If the base pairs match, the polymerase facilitates a reaction which forms a new bond between the 3 hydroxyl oxygen of the last nucleotide on the primer with the alpha phosphorus atom of the dntp This releases an inorganic phosphate as a product PRODUCTION OCCURS IN A 5 ->3 DIRECTION Thus, monomers can only be added to the 3 end of a primer

34 DNA Polymerase This reaction does not occur at any significant speed without DNA polymerase Fast and accurate Has ability to proofread

35 Polymerase Chain Reaction (PCR) Powerful technique used to replicate and amplify DNA in a test tube Allows for exponential amplification of a desired region of DNA

36 Problem #4: Adenine NH 2 N N N N DNA Identify all the hydrogen bond donors and acceptors and indicate which direction they point N N H N N H N DNA N N N H N N H DNA

37 Problem #4: Adenine Q: The exocyclic amine and the nitrogen directly attached to the DNA backbone have lone pairs, but these lone pairs do not serve as hydrogen bond donors. Why? A: These lone pairs are delocalized via resonance, so they no longer have the electron density necessary to form a hydrogen bond Q: Given the direction in which the hydrogen bond donors/acceptors point, why is it energetically favorable for the DNA bases to stack on top of one another A: All H-bond donors/acceptors are in the plane of the base; the top and bottom surfaces are therefore hydrophobic. This effect drives bases to stack in order to consolidate these hydrophobic surfaces

38 Problem 5: DNA Hybridization Q: DNA hybridization is energetically favorable. If you put DNA into ultra-pure water that contains no dissolved ions, DNA hybridization becomes unfavorable. Why? A: Under normal conditions, the negatively charged backbone will form electrostatic interactions with cations in solution. This stabilizes the structure by giving a net neutral charge. Without these cations, the negative backbones will repel.

39 Problem 6: DNA Replication Each DNA strand has a 5 and 3 end. These numbers refer to the numbering of the hydroxyl groups of the deoxyribose. Two DNA strands hybridize in an antiparallel fashion to form dsdna

40 Problem 6: DNA Replication Which of these strands are identical? Which are not? 5 -ATGGCCAT-3 3 -ATGGCCAT-5 5 -TACCGGTA-3 3 -TACCGGTA-5 Draw the complementary strand of DNA for the sequence 5 -ATTCAAGC-3 3 -TAAGTTCG-5 Draw the complementary strand of DNA for the sequence 5 -GCTTGAAT-3 3 -CGAACTTA-5 Are these two pieces of DNA the same or different?

41 Problem #7: DNA Polymerization Q: Why does DNA polymerization occur in the 5 -> 3 direction? A: Think about the primer and the dntp. The phosphate on the dntp is on the 3 hydroxyl of the primer, so a new bond can only be formed with the 5 end of the dntp

CHEM 109A Organic Chemistry

CHEM 109A Organic Chemistry https://labs.chem.ucsb.edu/zakarian/armen/courses.html Chapter 2 Acids and Bases Central to Understanding Organic Chemistry Draw the conjugate acid of each of the following: