Water and other inorganic molecules

Chapter 2

pages 21 - 29

Water

Most important molecule in all living tissues Solvent for many organic and inorganic molecules Polar properties of water confer “self-assembly” to

insoluble molecules Important for 3D structure of lipids and proteins

Dissociative properties of water leads to acid-base chemistry Add charges to previously uncharged molecules

Hydrophobic vs. hydrophilic

Panel 2-2 from Molecular Biology of the Cell (4th ed.) by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Hydrophobic vs. hydrophilic

Polar/ionic compounds soluble in water are called hydrophilic (“water loving”)

Large non-polar compounds insoluble in water are called hydrophobic (“water fearing”)

Lipids and proteins can have polar and non-polar regions that determine orientation or arrangement of these compounds in water

Large molecules with polar and non-polar regions are called amphipathic

Acid-base chemistry

Panel 2-2 from Molecular Biology of the Cell (4th ed.) by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Acid-base chemistry

[H+] is measured as pH = -log10 [H+] or [H+] = 10-pH

pH = 2 means [H+] = 10-2 M pH = 9.4 means [H+] = 10-9.4 M = 4 x 10-10 M pH 7.2 – 7.4 is normal range for extracellular fluids pH 7.0 – 7.2 is normal range for intracellular fluids

Dissociation of other compounds can alter this equilibrium Add protons to solvated molecules Remove protons from solvated molecules

Solvation

Solvation, also sometimes called dissolution, is the process of attraction and association of molecules of a solvent with molecules or ions  of a solute. As ions dissolve in a solvent they spread out and become surrounded by solvent molecules.

Acid-base chemistry

Acids tend to add or donate protons to water Decreases pH pH < 7.0 is called acidic

Bases tend to remove or accept protons from water Increases pH pH > 7.0 is called basic

Acids and bases have equilibrium: acid ↔ base + H+

Addition or removal of H+ ions can alter this equilibrium Low pH: bases readily accept protons and are converted into acids Low pH: solvated molecules increase in positive charge High pH: acids readily donate protons and are converted into bases High pH: solvated molecules increase in negative charge

Acid-base equilibrium

pH where acid-base pair has 50-50 equilibrium is called pKa Define association constant Ka for reaction HA ↔ H+ + A-

From chemistry Ka = [H+] [A-] / [HA]

Define pKa same as pH, pKa = -log10 (Ka)

Solve for concentration of reactants when pH = pKa pKa = -log10 ([H+] [A-] / [HA])

pKa = -log10 [H+] - log10 [A-] + log10 [HA]

pKa = pH - log10 [A-] + log10 [HA]

When pH = pKa, then log10 [A-] = log10 [HA] or [A-] = [HA]

Therefore concentration of acid HA equals concentration of base A- when pH = pKa

Given HA ↔ H+ + A- where pKa of HA is 10.7, solution pH is 10.7, what is [HA] relative to [A-] at equilibrium?

1 2 3

33% 33%33%1. [HA] < [A-]

2. [HA] = [A-]

3. [HA] > [A-]

pH/pKa problems

Definition of pKa means acid concentration [HA] equals base concentration [A-] when pH = pKa

How can we calculate relative amount of acids and bases when pH ≠ pKa?

Ex: consider HA ↔ H+ + A- where pKa of HA is 4.5, solution pH = 8.3 Is there more HA or A- in this solution?

Ex: consider HA ↔ H+ + A- where pKa of HA is 4.5, solution pH = 2.3 Is there more HA or A- in this solution?

pH/pKa problems

Start at pH = pKa with a 50-50 equilibrium of acid/base Consider whether solution pH produces excess or lack of H+

relative to compound pKa Ex: pKa = 4.5, pH = 8.3, lack of H+ relative to pKa since pH > pKa Ex: pKa = 4.5, pH = 2.3, excess of H+ relative to pKa since pH < pKa

Determine how direction of equilibrium of HA ↔ H+ + A- shifts due to excess or lack of H+

Excess protons shift equilibrium toward HA or acid formation Lack of protons shifts equilibrium toward A- or base formation

Can verify results using charge of dominant species Excess protons make solvated species more positive Lack of protons makes solvated species more negative

Can also verify using pKa = pH - log10 [A-] + log10 [HA]

pH/pKa problems

Ex: HA ↔ H+ + A- where pKa of HA is 4.5, solution pH = 8.3 Start at pH = pKa = 4.5, 50-50 split between acid HA and base A-

Raising solution pH from 4.5 to 8.3 produces lack of protons Then the base A- is the dominant species at equilibrium Verify with charge: dominant species A- is more negative than HA Also 4.5 = 8.3 - log10 [A-] + log10 [HA], therefore log10 [A-] > log10 [HA]

Ex: HA ↔ H+ + A- where pKa of HA is 4.5, solution pH = 2.3 Start at pH = pKa = 4.5, 50-50 split between acid HA and base A-

Lowering solution pH from 4.5 to 2.3 produces excess of protons Then the acid HA is the dominant species at equilibrium Verify with charge: dominant species HA is more positive than A-

Also 4.5 = 2.3 - log10 [A-] + log10 [HA ], therefore log10 [HA] > log10 [A-]

Given HA ↔ H+ + A- where pKa of HA is 10.7, solution pH is 7.3, what is [HA] relative to [A-] at equilibrium?

1 2 3

33% 33%33%1. [HA] < [A-]

2. [HA] = [A-]

3. [HA] > [A-]

Physiologic pH and protonation

Extracellular pH is tightly regulated between pH 7.2 – 7.4 Adding acidic and basic compounds will not change pH significantly

Pulmonary and renal reflexes to maintain pH will be discussed later in the semester

More convenient to look at whether acidic or basic compounds will accept or donate protons at physiologic pH Tells us whether a compound will carry extra positive charge

Diagram below shows relative % of compound in protonated (+) form based on magnitude of compound pKa relative to physiologic pH

Forms a continuum of compounds that are 0% → 100% protonated (+) as the pKa of the compound increases from below 7.3 to above 7.3

pH 7.3

pKa = 7.3~50% (+)

pKa < 7.3< 50% (+)

pKa > 7.3> 50% (+)

pKa >> 7.3~100% (+)

pKa << 7.3~0% (+)

pKa of organic compounds

Various organic molecules have acidic or basic regions Acidic carboxyl group: R-COOH ↔ R-COO- + H+

pKa typically < 4, varies with composition of side group R

Produces lack of protons going from pKa = 4 to pH = 7.2

Vast majority are negative R-COO- at physiologic pH 7.2 – 7.4

Basic amine group: R-NH3+ ↔ R-NH2 + H+

pKa typically > 10, varies with composition of side group R

Produces excess of protons going from pKa = 10 to pH = 7.2

Vast majority are positive R-NH3+ at physiologic pH 7.2 – 7.4

Charged acidic or basic regions very important for protein structure

pKa of H2O

H2O can serve as both acid and base Amphoteric compounds can serve as both acids and bases

Water as a base: H2O + H+ ↔ H3O+ pKa << 7, this is pH where [H2O] = [H3O+] Remember [H2O] >> [H3O+] at pH 7 Requires excess of H+ to protonate H2O so that [H2O] = [H3O+]

Water as an acid: H2O ↔ H+ + OH- pKa >> 7, this is pH where [H2O] = [OH-] Remember [H2O] >> [OH-] at pH 7 Requires lack of H+ to remove H+ from H2O so that [H2O] = [OH-]

pKa of H2O

Why isn’t the pKa of H2O equal to 7? Adding other species to solution brings solution pH

toward species pKa The pH of pure H2O is 7

Remember H2O can simultaneously accept and donate protons

Simultaneously moves water pH in two directions Toward H2O + H+ ↔ H3O+ pKa << 7 Toward H2O ↔ H+ + OH- pKa >> 7

Charged acids and bases

Acids and bases can be neutral or charged Started using example HA ↔ H+ + A-

Has neutral acid HA, negative base A- Reaction could also be HA+ ↔ H+ + A

Has positive acid HA+, neutral base A Acids can be neutral or (+) but not (-)

Difficult to pull H+ from (-) compound Bases can be neutral or (-) but not (+)

Difficult to add H+ to (+) compound Important to identify charges on acid/base pairs

Which compound is most likely to act as a base?

1 2 3

33% 33%33%1. HPO4

2-

2. NH4+

3. H2S

Strength of acids and bases

Strength of acids and bases determined by propensity to donate/accept protons

Strong acids can donate protons in acidic environment Have pKa << 7 and donate all protons at neutral pH

Water is a weak acid: H2O ↔ H+ + OH- has pKa >> 7

Strong bases can accept protons in basic environment Have pKa >> 7 and are protonated at neutral pH

Water is a weak base: H2O + H+ ↔ H3O+ has pKa << 7

Which value is closest to the pKa of HCl?

1. 2. 3. 4.

25% 25%25%25%1. 1.5

2. 6.3

3. 9.5

4. 13.8

Other inorganic molecules

Mostly soluble metallic ions Cations and anions, monovalent and divalent Common ones are H+, Na+, K+, Ca2+, Mg2+ and Cl-

Trace metals such as Fe3+ and Zn2+ also play important roles in physiological function

Molecular ions ammonium NH4+, bicarbonate

HCO3-, and phosphate PO4

3-

Covalent bonds in HCO3- and PO4

3- have resonance structures that promote stability

Phosphorylation

Panel 2-1 from Molecular Biology of the Cell (4th ed.) by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter