Lecture 1: Chemical Properties + Lecture 2: Intro to biochemical principles Flashcards
Water can form hydrogen bonds:
-between water and alcohol, between water and amino acids and between water and sugar
Hydrophilic
- Water loving
- Drugs that are hydrophilic(soluble in water) tend to stay in the blood circulation and surrounding interstitial tissue
- Polar molecules ( not = sharing of e-)
- Molecules with a lot of hydroxyl groups
- more soluble in body fluids
- Ex: Glucose
- will have trouble passing through lipid membranes
Hydrophobic
- Water fearing
- Drugs that are hydrophobic tend to get trapped inside the tissue and are slowly eliminated
- Non polar molecules (= sharing of e-
- less soluble in body fluids but can pass lipid membrane
- Ex: Benzene
- can pass through lipid membranes
Ion channels are
Hydrophobic on the outside and hydrophilic on the inside
Lipid Bilayer in water has
Hydrophilic heads and hydrophobic tails
- aqueous around
pH =
- log [H+]
- pKa + Log [A-] / [HA]
A low pH means
- more hydrogen ions
- more acidic
A high pH means
- less hydrogen ions
- more basic
Ka
Dissociation constant
pKa
- log [Ka]
- Tells you how strong the acid is
- pH at which conc. of acid HA equals that of its conjugated base A-
The stronger the acid
- the larger Ka value
- easier to dissociate and fully dissociates in sltn
–the smaller the pKa and pH
The weaker the acid
- a smaller Ka value
- harder to dissociate (partially dissociates)
–the larger the pKa and pH
If pH=pKa
the charged species = uncharged species
if pH is lowered
molecule becomes more protonated
If pH is raised
molecule becomes more de-protonated
pKa of amide is
pKa of carboxylic acid
9-10
4-5
Partition coefficient
- Describes the extent to which an uncharged compound dissolves in an aqueous solvent versus organic solvent
Water phase vs octanol phase
Hydrophilic molecules will partition more into water phase. Hydrophobic molecules will partition more into octanol phase
Small molecule drugs are
less than 500 Daltons. Large molecule drugs are over 500 Daltons
For acids,
pH > pKa charge is negative
pH < pKa charge is neutral
For bases,
pH > pKa charge is neutral
pH < pKa charge is positive
Lowering pH
shifts equilibrium to the left
-More of the carboxylic acid becomes protonated and is in its neutral form
Raising pH
shifts equilibrium to the right
- More of the carboxylic acid dissociates and forms a negatively charged species
Strength of interactions
- Covalent
- Ionic
- Hydrophobic
- Hydrogen
- Van der waals
Tertiary proteins have
non-covalent bonds and disulfide bridges
Buffer solutions
-resist pH change following the addition of a strong acid or base
Physiologic buffers
include bicarbonate, orthophosphate, and proteins
Ion
when an atom loses or gains an electron
Anion
negatively charged ions
gains an electron
Cation
loses an electron
becomes positively chaged
The charge of the nucleus of an atom
positively charged
Covalent bonds
sharing of electrons between atoms
- very strong bonds
Electronegativity
tendency for an atom to attract a bonding pair of electrons
- atoms affinity for electrons
Trend is F>O>N»>C>H
Polar vs nonpolar molecules
Polar: Unequal sharing of electrons
Non-polar: electrons are shared equally between carbon atoms in a carbon bond
Dipole-Dipole
attractive forces between the positive end of one polar molecule and the negative end of another polar molecule
- weak, distance dependent interactions
Hydrogen bonding
when a H atom is attached to a highly electronegative element such as N or O that is in proximity to another electronegative atom with a lone pair of e-
Charge on Amines and Carboxylic Acids
An amine can gain a proton to become positively charged (NH2→ NH3
+)
A carboxylic acid can lose a proton to become negatively charged (COOH→ COO-)
What is an acid?
An acid is a proton donor
• Example: Hydrochloric acid (HCl), acetic acid (CH3COOH)
• Hydrochloric acid: HCl→H+ + Cl-
What is a base?
- A base is a proton acceptor
- Example: Sodium hydroxide (NaOH), ammonia (NH3)
- Ammonia: NH3 + H2O→ NH4+ + OH-
What is meant by a weak versus strong acid/base in terms of dissociation
A strong acid/base fully dissociates in solution
Hydrochloric acid: HCl→H+ + Cl-
A weak acid/base only partially dissociates in solution
Some of the acid/base will separate and form ions
• Some of the acid/base will remain as a neutral complex
• acetic acid CH3COOH →H+ + CH3COO-
Reversibility
Gain and loss of protons on weak acids/bases are are reversible reactions and there exists an equilibrium between the charged and neutral forms
Ex: A neutral carboxylic acid can lose a proton (+) to become negatively charged (COOH→ COO-)
• A negatively charged carboxylic acid can gain a proton(+) to become neutral (COO- → COOH
pH
- based on hydrogen ion conc.
- -log[H+]
- can be changed by adding acid/base
If we protonate an amine, it becomes
positively charged
Intermolecular Interactions
dictate various properties of a molecule, including its solubility and interaction with biological drug targets
• Drug A: 1 g/100 mL water
• Drug B: 10 g/100 mL water
Which drug is more soluble?
Drug B
We can get more of a mass into a lower volume of water
Solubility
How much of a solute can be dissolved in a solvent
to make a solution
Biochemistry
the study of chemical process in living
organisms
Drugs that are hydrophilic
tend to stay in the blood circulation and surrounding interstitial tissue
Drugs that are hydrophobic
tend to get trapped
inside the tissue and are slowly eliminated
Why is it that water can easily break apart
NaCl but can not cleave an amide bond
without the help of a catalyst?
The water molecule has greater electronegativity than Cl
- bc of ionic interactions
Nucelophile
electron rich molecules
- negatively charged or that has lone pairs of electrons
Electrophile
electron poor molecules
- attracts electron rich molecules
- positively charged or neutral w no one pairs of e-
Pepsin
an enzyme that degrades proteins into smaller
peptides in the stomach and digestive system
Water can act both as
an acid and as a base, an equilibrium between hydronium ion (H3O+) and a hydroxide ion (OH−)
- water has the ability to ionize
pOH
-log [OH-]
Kw=
[H+] [OH-] = 10^-14
pH + pOH = 14
To calculate the pH of a NaOH solution you need to know its A. Molarity B. Density C. Volume D. All the above
A. Molarity
Buffer solutions
they resist to pH change because of the presence of an equilibrium
between the acid HA and its conjugate base A−
- the ability to resist a change following addition
of a strong acid or base
What helps to maintain pH of plasma (blood) around 7.4
Carbonic acid (H2CO3) and Bicarbonate ( HCO3-)
Hydrogen bond donors vs. Hydrogen bond acceptors
Donors: O or N that is covalently bonded to H
Acceptors: H bonds
Water can serve as a donor and acceptor
