Molecular Medicine MOL 114

Fall Semester 2015

Director: Rajaa Fakhoury, Ext. 8941 rfakhoury@alfaisal.edu
 Physical & chemical properties of water (H2O)
Key Concepts

Water molecules are polar

Water can form hydrogen bonds with other molecules

Polar and ionic substances can dissolve in water

Nonpolar substances cannot dissolve in water – hydrophobic effect

Amphipathic substances (polar & nopolar segments) form micelles or bilayers

Water moves by osmosis and solutes by diffusion

Water disassociates H+ & OH- - pH

Contact: Peter Kvietys – ext 7673; email: pkvietys@alfaisal.edu

 Physical & chemical properties of water (H2O)

H2 O
central to
biochemistry
for 3 reasons

1) Biomolecules assume shape/function due to physical/chemical properties of H 2O

2) H2O is the medium for the majority of biochemical reactions

3) H2O itself actively participates in chemical reactions

CO2 is linear no unpaired electrons

H2O is non-linear :
Unpaired electrons repel

H2O is polar:
Electrons more strongly attracted
to oxygen
 hydrogen covalent
Bond Bond
↓ ↓

Water molecule has an angular geometry

density of electrons unevenly distributed

Water is a polar molecule: 2 unbound electron pairs on oxygen

unshared electrons on O (negative charge, δ-)
the 2 H (positive charge, δ+)
Hydrogen bonds – 1/20 the strength of covalent
bonds
- can form 2 hydrogen bonds
Each water molecule
– maximum of 4 hydrogen bonds
 Water as a solvent

Solubility:

solvent – solute interactions

stronger than

solute – solute interactions

Ionic interaction
Ionic bond or interaction Hydrogen bonds
Hydrogen bonds can form between hydroxyl
a “donor” group N – H , O – H carbonyl
and an “acceptor” group N, O

acceptor donor

donor ( ); acceptor ( )

amino
carboxyl

Sometimes SH can be a donor group

The higher the proportion of polar

functional groups in a molecule
the more hydrophilic
 Hydrophobic effect
Hydrophobic:
Molecules consisting of mainly hydrocarbons are poorly soluble in water
Nonpolar groups can’t form hydrogen bonds (e.g, hydrocarbon tails of lipids, steroids)

Triacylglycerol
(glyceryl tripalmitate)

The longer the chain

the more hydrophobic
“Cage” of H₂O around nonpolar solute
 Hydrophobic effect
The tendency for water to minimize its contact
with hydrophobic (nonpolar molecules)

8 x 1 ml 1 x 8 ml

Surface area 40 cm² 20 cm²

Aggregation and displacement reduces surface area for lipid-water interaction

 Amphipatic (amphiphilic) biomolecules
Most biomolecules contain both polar and nonpolar groups
both hydrophobic & hydrophilic – “amphipathic” or “amphiphilic”

Nonpolar
Hydrophobic
Fatty acid soap
Polar
Hydrophilic

Nonpolar
Hydrophobic
Phospholipid
Polar
Hydrophilic

Lecithin; phosphatidylcholine
Amphipathic substances form structurally ordered aggregates

Low
“cages” Low

polar water

Phospholipid
nonpolar concentration
↑↑↑i

High

High
 Water moves by “osmosis”

What about a cell membrane (lipid bilayer) ?

Water moves by osmosis across cell membranes

Water moves across cell membranes

via protein channels – “aquaporins”
Water moves by osmosis across cell membranes

[Solute] [Solute] [Solute]

outside = inside outside > inside outside < inside

Cell volume Cell volume Cell volume

no change decrease increase
Solutes move by diffusion

Dialysis – kidney failure

Hemodialysis
 Peritoneum serves as a
semi-permeable membrane

e.g., urea can get across

Not covered in class

Do not have to know for exam!

Water ionizes (dissociates) to form H+ & OH-
Water has a slight tendency to ionize

common expression

H2O H+ + OH-
proton hydroxide
ion

Reality: no free protons

2H2O H3O+ + OH-

hydronium
ion
 Water ionizes (dissociates) to form H+ & OH-
Equilibrium expression for dissociation of water
– dissociation constant

Dissociated

Un-dissociated

[H₂O] is much greater than the component ions

– considered constant & incorporated into K → Kw

The ionization constant of water, KW , is 10⁻¹⁴ (25⁰ C)

Pure water has equimolar amounts of H⁺ (10⁻⁷ M) & OH⁻ (10⁻⁷ M)

[H⁺] = (10⁻⁷ M) → neutral [H⁺] > (10⁻⁷ M) → acidic [H⁺] < (10⁻⁷ M) → basic
Water ionizes (dissociates) to form H+ & OH-

Pure water → [H⁺] = 1 x 10⁻⁷ M or 0.0000001 M

cumbersome

exponent without minus sign is pH

[H⁺] = 1 x 10⁻⁷ = pH 7.0

The higher the [H⁺] the lower the pH

Log table

# log

100 +2

10 +1

101 0

0.1 -1

↑ [H⁺] 10X then pH ↓ by 1 unit

↓[H⁺] to 1/10 than pH ↑by 1 unit

 Gastric Pancreatic
Bodily fluid pH enzyme enzyme

Blood 7.4

Gastric juice 1.5 – 2.0

Pancreatic juice 7. 6 – 8.4

 Acids & bases alter pH
Acid – substance that can donate a proton
Base – substance that can accept a proton

HA + H2O H3O+ + A-
acid base conjugate conjugate
acid base

Assuming H₂O is involved in acid-base reactions:

HA H+ + A-
acid proton conjugate
base
 Acids & bases alter pH

Dissociation constant

[H₃O⁺] [A⁻] products

Ka =
[HA] [H₂O] reactants

Assuming H₂O is always involved:

[H⁺] [A⁻] High Ka then strong acid

Ka = [HA]

Ka values cumbersome - for convenience log form

pK = – log K or log 1K
Low pK then strong acid
 Acids & bases alter pH

[H⁺] [A⁻] [HA]

rearrange [H⁺] = Ka
Ka = [HA] [A⁻]

Negative log of each term Substituting pKa for – log Ka

[A⁻]
pH = – log Ka + log
[HA]
[A⁻]
pH = pKa + log [HA]

Henderson-Hasselbalch equation
 Log table
# log

10 +1

11 0

0.1 -1

If pH = pK then A- = HA

[A⁻] If pH > pK then more A⁻ (less protonated)

pH = pKa + log [HA]
If pH < pK then more HA (more protonated)
 Buffers prevent drastic changes in pH
with addition of either acid or base

Buffers most effective in maintaining pH

When pH is ≈ pK