Noncovalent Molecular Forces - Part 1 Lecture Supplement page 200 F-F-        

Chemistry 14C Part 3 Structure Controls Everything Physical properties Boiling point Solubility etc. Chemical properties Reactions Reactivity Biological properties Drug effects etc. +  Ring strain allows irreversible enzyme inhibition Influence antibiotic behavior Example: Penicillin G (an antibiotic) Salt enhances water solubility

Noncovalent Molecular Forces Why should I study this? Noncovalent forces control association of molecules which causes Physical properties: Melting point, boiling point, solubility, etc. Molecular organization into larger structures: Membranes, etc. Molecular recognition: Substrate/enzyme docking, etc. Definition: Attractive forces (other than covalent bonding) between atoms or molecules

How Do We Measure Noncovalent Forces? Consider evaporation of water... Evaporation add energy Liquid water Stronger attraction= more energy required to disrupt attraction = more energy needed for evaporation = higher boiling point (bp) Boiling point easily measured Therefore bp a useful approximation of attractive forces Covalent bonds still intact Water vapor Attractive force disrupted Attractive force keeps molecules close

How Do We Measure Noncovalent Forces? Boiling point (bp) : Temperature at which vapor pressure of substance = ambient pressure Melting point (mp): Influenced by... Attractive forces Crystal packing Therefore mp is ambiguous measure of attractive forces } What Kinds of Noncovalent Forces Occur? Consider these substances: NaCl bp 1413 o C H 2 O bp 100 o C BrF bp 22 o C Ar bp -186 o C Increasing boiling point indicates increasing magnitude of attractive forces

NaCl bp 1413 o C = Na + = Cl - What attractive force is operating? What is the nature of association between Na and Cl? Cl Na EN  EN = = 2.1 Attractive force = ionic bond = anion-cation = electrostatic (opposite charges attract) Evaporation or melting = separating opposite charges NaCl evaporates as Na + and Cl - not Na-Cl NaCl heat of vaporization = 188 kcal mol -1 High bp and mp typical of ionic compounds

Ionic versus Covalent Bonds Chemical bond = sharing of electron pair Increasing  EN causes Increasing ionic (polar) character  EN Bonding Nonpolar covalent Slightly polar covalent Moderately polar covalent bond Highly polar covalent bond Slightly ionic bond Highly ionic bond Reducing bond length reduces polarity Example: C – H  EN = 0.4; short bond  polarity Ionic bond: Highly unequal sharing of electron pair Covalent bond: Approximately equal sharing of electron pair

BrF bp 22 o C (liquid at room temperature) What attractive force is operating? EN  EN = = 1.2 = not ionic = polar covalent   Attractive force= dipole-dipole = electrostatic (  + /  - ) Bp suggests dipole-dipole attraction weaker than cation-anion   F Br What is the nature of association between Br and F?

H 2 O bp 100 o C (liquid at room temperature) What attractive force is operating?  EN = = 1.4 = not ionic = polar covalent       Attractive force= electrostatic = dipole-dipole = hydrogen bonding H O EN What is the nature of association between H and O?

Hydrogen Bonding       In general... Hydrogen bonding requires a donor and an acceptor XH A Must have large  + X = high EN = F, O, N (rarely anything else) Hydrogen bond acceptor Has high electron density to attract  + Must have lone pair Can be small, neutral atom: O or N Or can be any anion Examples: H 2 O, (CH 3 ) 3 N, I - Hydrogen bond donor

Hydrogen Bonding Common attractive force Important in biology Also influences protein structure Hydrogen bond strongest when linear F-F-         Adenine Thymine |||||| Dynamic: H-O-H OH 2 ~3 x s lifetime Not always dipole-dipole Example: F - in CH 3 CH 2 OH Many O-H, N-H, H 2 O in organisms Example: DNA base pairs

Adenine ThymineGuanine Cytosine Fig Vollhardt

Ar bp -186 o C (monoatomic gas at room temperature) What attractive force is operating? Ionic? No electronegativity difference  no ions Dipole-dipole? No covalent bonds  no bond dipoles Hydrogen bonding? No hydrogens No attractive force? = no energy required for vaporization? Bp -186 o C > -273 o C (absolute zero) Therefore some attractive force must be present Bp is very low so attractive force must be weak Student homework: Figure out what attractive force exists between two Ar atoms

Noncovalent Molecular Forces - Part 2 Lecture Supplement page 206

Summary of Part 1 Physical properties such (boiling point, solubility, etc.) controlled by noncovalent association Ar bp -186 o C Noncovalent attractive force = ? H-bonds of wide biological importance: Protein and DNA structure etc. Stronger attractive force = more energy required for vaporization = higher boiling point Noncovalent attractive forces caused by electrostatic attractions Examples NaClbp 1413 o CNoncovalent attractive force = anion-cation BrF bp 22 o CNoncovalent attractive force = dipole-dipole H 2 O bp 100 o CNoncovalent attractive force = hydrogen bonding H-bond donor usually O-H or N-H bond or any anion with lone pair H-bond acceptor = neutral atom with lone pair and high  - = O or N

Ar bp -186 o C (monoatomic gas at room temperature) Ionic? Dipole-dipole? Hydrogen bonding? No attractive force? = no energy required for vaporization? bp -186 o C > -273 o C (absolute zero) so some weak attractive force must be present Ar ball of electrons e-e- e-e- e-e- e-e- Ar e-e- e-e- e-e- e-e- e-e- e-e- e-e- e-e-     e-e- e-e- e-e- e-e- Induced charges Momentary electrostatic attraction } Weak force Called London force All molecules have electrons so all molecules influenced by this force What attractive force is operating?

Strength of London Forces What influences strength of London forces? Boiling point -269 o C -246 o C -186 o C -152 o C -107 o C -62 o C Atomic radius 0.32 Å 0.69 Å 0.97 Å 1.10 Å 1.30 Å 1.45 Å Increasing attraction Increasing ease of electron cloud distortion Polarizability : Ability to distort electron cloud Distortion easy = soft Example: Rn Distortion difficult = hard Example: He Larger atomic radius = softer Larger electronegativity = harder Surface area effect? What controls polarizability?

Strength of London Forces Compare molecules with same polarizability but different surface areas Hydrogens = small = hard Boiling point: -162 o C -88 o C -42 o C -0.5 o C Surface area: 56.6 Å Å Å Å 2 CH 4 CH 3 CH 3 CH 2 CH 3 CH 3 CH 2 CH 2 CH 3 Conclusion Increasing surface area = increasing London force Maybe just a molecular weight effect? Surface area effect? MW:

Strength of London Forces Compare molecules with same polarizability and different surface areas, but same molecular weight, such as isomers of C 5 H 12 Boiling point: 36 o C 30 o C 9.5 o C Shape: Most elongated Most spherical Highest surface area Lowest surface area Molecular weight effect? Conclusion Higher surface area = _______________ attraction = ________________ London forces 2-MethylbutanePentane2,2-Dimethylpropane stronger

Other Noncovalent Interactions Ion-dipole Cation-pi Cation attracted to pi electron cloud Cl - Na + H H   O  Explains water solubility of NaClImportant in some enzyme-substrate binding K+K+ Aromatic ring pi cloud Bond dipole attracted to anion or cation Example: Na + and Cl - in water

Other Noncovalent Interactions Also called aromatic stacking Aromatic rings Pi stacking Important in DNA

Relative Strength of Noncovalent Forces When more than one force operates, strongest force dominates Example: In CH 3 OH evaporation, H-bonding harder to overcome than London forces Approximate ranking of noncovalent force strengths useful Cation-anion (ionic bonds) Covalent bonds Dipole-dipole Hydrogen bonding Ion-dipole Cation-pi Pi stacking London forces Strongest force Weakest force >>

Application of Noncovalent Interactions: Solubility Water + Acetic acid + Oil (glycerol tristearate) Oil layer Vinegar layer (water + acetic acid) Questions Why acetic acid dissolves in water? Why oil does not dissolve in water?

Application of Noncovalent Interactions: Solubility What causes one substance to dissolve in another? Two layers A and B immiscible Homogeneous A and B dissolve Dissolving: A interrupts attractive forces in B Soluble: A/B attractions better than A/A and B/B attractions Insoluble: A/B attractions not better than A/A and B/B attractions “Better” = stronger attractions and/or more attractions AAAAAAAAAAAAAAAAAA BBBBBBBBBBBBBBBBBB ABABABA BABABAB ABABABA Solubility is an equilibrium issue...

Application of Noncovalent Interactions: Solubility Many attractive interactions Water + CH 3 COOH soluble Polar bonds Hydrogen bond acceptor Hydrogen bond donor Water + acetic acid: Poor attraction between oil and water Strong attraction between water and water Water + oil insoluble Water + oil: Like dissolves like

Melamine- Melamine Solubility in water: 3.2 g/L Cyanuric Acid Solubility in water: 2.7 g/L

Melamine cyanurate Insoluble in water…