1. Biochemist’s View of the DNA Double Helix Major groove Minor groove

2. Representative Nucleotides 5’ 3’ 2

3. Chemist’s View

4. Contrast with Nucleic Acid Bases (A, T, C, G, U) – Specific! Evidence for specificity? Why are these interactions specific? e.g. G-C & A-T

5. Evidence? –If mix G & C together → exothermic reaction occurs; change in 1 H chemical shift in NMR; other changes  reaction occurring –Also occurs with A & T –Other combinations → no change! e.g. Guanine-Cytosine: Why? –In G-C duplex, 3 complementary H-bonds can form: donors & acceptors = molecular recognition

6. Mechanism?

7. Properties of Pyridine We’ve seen it as an acid & an H-bond acceptor Lone pair can act as a nucleophile:

8. Another example of N-Alkylation of Pyridines This is an S N 2 reaction with stereospecificity