Levels of Biochemistry

R-S-RThioether

Lewis Structures Consider outer shell valence electrons only

H, Na, K have 1 electron Mg, Ca have 2 electrons B has 3 electrons C, Si have 4 electrons N, P have 5 electrons O, S, Se have 6 electrons Cl, I have 7 electrons

Na + + e - + e - -

Na +

+

+ Each atom has an octet

Count the number of protons (+1) Count the unshared electrons (-1) Count the shared electrons (-0.5) Assigning Formal Charges to Atoms Protons+7 Unshared e- -6 Shared e- -1 Formal charge 0

Formal charge on oxygen Protons+6 Unshared -4 Shared -2 Total 0 Formal charge on oxygen Protons+6 Unshared -4 Shared -2 Total 0 Formal charge on oxygen Protons+6 Unshared -6 Shared -1 Total -1

Formal charge on nitrogen Protons+5 Unshared 0 Shared -4 Total+1

Oxidation States Electrons in a bond belong to the more electronegative atom For atoms that are equivalent then the electrons are split between them

Lewis structures tell you about reactivity Resonance

+- Good Resonance Structures maximize covalent bonds surround 2nd and 3rd row atom with octets minimize charges place negative charges on electronegative atoms - +

Moving electrons The curved arrow formalism + H + - -

When drawing mechanisms: Protons do not appear out of nowhere Protons do not disappear into thin air Double headed arrows indicate the movement of 2 electrons Single headed arrows indicate the movement of 1 electron

Nucleophiles and electrophiles Nucleophile –An atom that bears a lone pair of electrons –A resonance form that places a lone pair on an atom –An atom that bears an acidic proton that when it departs leaves behind a lone pair

Atom that bears a lone pair of electrons + H + -

Resonance structure that places a lone pair on an atom + - Nucleophile

Acidic proton that leaves and generates a lone pair -

Sometimes you need a very strong base to make the third type of nucleophile pKa = 45 No resonance Resonance - -

How to choose which nucleophile is better Two nucleophiles

H+H+ No resonance + + +

Biologically important nucleophiles.

Nucleophiles and electrophiles Electrophile –An atom that bears a vacant orbital –A resonance form that generates a vacant orbital –An atom that bears a leaving group that when it departs generates a vacant orbital

Atoms with vacant orbitals + Nu: -

Resonance structures that generate vacant orbitals + -

Atoms that bear leaving groups that when they depart leave a vacant orbital H+H+ - + electrophile Leaving group

Electrophilicity ≠ positive charge Nucleophilicity ≠ negative charge

Biologically important electrophiles.

Chiral Molecules Carbon atoms that have 4 distinct substituents cannot be superimposed on their mirror image.

Molecules with more than one stereocenter Molecules that differ in only one stereocenter are stereoisomers Diastereomers are stereoisomers that have the same configuration at one stereocenter but different configurations at another Enantiomers have opposite configuration at all stereocenters

Chiral molecules are optically active: the different stereoisomers rotate the plane of polarized light in opposite directions

Dextrorotary: + rotation of the plane of light Levorotary: - rotation of the plane of light D-enantiomer L-enantionmer This does not tell us anything about the absolute configuration of a molecule.

Cahn-Ingold-Prelog SH > OH > NH 2 > COOH > CHO > CH 2 OH > C 6 H 5 > 2 H > 1 H Rank atoms directly attached to the chiral center and assign priorities based on decreasing atomic number If a decision cannot be reached then move on to the second atom away from the chiral center Multiple bonded atoms are considered an equivalent number of singly bonded atoms = > Therefore

Cahn-Ingold-Prelog

Clockwise R Counterclockwise S

WATER: Molecule of the year…decade…century…millenium… er…all time

Structure of ice.

Structures of the water trimer, tetramer, and pentamer.

Water is a rapidly fluctuating network of hydrogen bonding H 2 O molecules that reorder every ~ s

D = Dielectric Constant Ability to keep opposite charges apart Generally increases with dipole moment F = kq 1 q 2 Dr 2 F = force q = charge k = constant r = distance

Dielectric Constants and Permanent Molecular Dipole Moments of Some Common Solvents.

D for water is among the highest even though the dipole is not the strongest. Why?

Water is highly ordered and resists thermal randomization that decreases the dielectric constant

Solvation (hydration) of ions by oriented water molecules.

Hydrogen bonding by functional groups.

Hydrogen bonds are weak Van der Waals forces – kcal mol -1 O … H hydrogen bond – 1-3 kcal mol -1 C-H covalent bond –100 kcal mol -1

Associations of amphipathic molecules in aqueous solutions.

Ionic Mobilities in H 2 O at 25°C.

Mean lifetime of a hydronium ion is s This makes proton transfer reactions (acid base reactions) among the fastest in aqueous solutions.