Physicochemical Flashcards
interdisciplinary science at the intersection of organic chemistry, biochemistry (biochemistry), computational chemistry, pharmacology, molecular biology and physical chemistry
Medicinal Chemistry
Involved with the identification, design, synthesis and development of new drugs that are safe and suitable for therapeutic use in humans and pets
Medicinal Chemistry
Study of marketed drugs, their biological and their quantitative structure-activity relationships (QSARs)
Medicinal Chemistry
Studies how chemical structure influences biologic activity
Medicinal Chemistry
Studies How the molecular and physicochemical properties of the molecule influences the drug’s pharmacokinetics (ADME) and pharmacodynamics (what the drug does to the body).
Medicinal Chemistry
how functional groups present within the molecule influence its acid-base properties, water solubility, partition coefficient, crystal structure, stereochemistry, and ability to interact with biologic systems, such as enzyme active sites and receptor sites
Physicochemical
relationship of how structural features of the molecule contribute to, or take away from, the desired pharmacologic properties
Structure-activity relationships (SARs)
influences the biologic activity of chemical entities and that alterations in structure produce changes in biologic action.
Molecular structure
“one chemical group gives one biological action”
Postulate
developed the concept of drug receptors
Ehrlich (Paul Ehrlich)
Interaction of the chemical with the cell surface “side chains” produces a what
Toxic effect
Selectivity permitted eradication of disease states without significant harm coming to the organism being treated.
Selective Toxicity (albert)
The underlying principle of medicinal chemistry
Structure-Activity Relationships
T or F. Similar molecules exert similar biologic action in a qualitative sense
T. SAR
groups within a specific structure are important for its pharmacologic activity and how these groups can be modified to produce more potent, mode selective, and safer compounds
Functional Groups
Example of drugs with structural similarity:
PABA and sulfanilamide
How can drug molecules exhibit their pharmacologic activity?
By interacting with a biologic target , typically a receptor, enzyme, nucleic acid, or excitable membranes or other biopolymer
The relative fit of each drug molecule with its target is a function of a number of what
Physicochemical properties
What are the three physicochemical qproperties
1.Acid-base chemistry and related ionization
2. Functional group shape and size
3. Three dimensional-spatial orientation
are natural polymers produced by the cells of living organisms.
Biopolymers
consist of monomeric units that are covalently bonded to form larger molecules.
Biopolymers
Most appropriate to explain and predict acid-base behavior
Bronsted-Lowry acid-base theory
When an acid gives up a proton to a base, it is converted to its what
Conjugate base
any substance capable of yielding a proton (H+)
- Based on BLABT
Acid
any substance capable of accepting a proton
- according to BLABT
Base
When a base accepts a proton, it is converted to its whatt
Conjugate acid
T or F. When a basic functional group is converted to the corresponding conjugate acid, it too become unionized.
F. Ionized
Functional groups that cannot give up or accept a proton are considered to be ___ with respect to their acid-base properties.
“neutral” (or “nonelectrolytes”)
Acids and Conjugate Base
Phenol (9-11)
Phenolate
Sulfonamide (9-10)
Sulfonamidate
Imide (9-10)
Imidate
Alkylthiol (10-11)
Thiolate
Thiophenol (9-10)
Thiophenolate
N-Arylsulfonamide (6-7)
N-Arylsulfonamidate
Sulfonimide (5-6)
Sulfonimidate
Alkylcarboxylic acid (5-6)
Alkylcarboxylate
Arylcarboxylic acid (4-5)
Arycarboxylate
Sulfonic acid (0-1)
Sulfonate
Common basic functional groups and conjugate acid
Arylamine
Arylammonium
Aromatic amine (5-6)
Aromatic ammonium
Imine (3-4)
Iminium
Alkylamines
Alkylammonium
Amidine
Amidinium
Guanidine
Guanidinium
Neutrals
Alkyl Alcohol
Ether
Ester
Sulfonic acid ester
Amide
Diarylamine
Nitrile
Quaternary ammonium
Amine oxide
Ketone and aldehyde
Thioether
Sulfoxide sulfone
A molecule can contain multiple functional groups with acid-base properties and, therefore, can possess both acidic and basic character. T or F
T
Examples of molecule containing multiple functional groups with acid-base proteins
Ciprofloxacin, (a fluoroquinolone antibacterial agent)
are weakly basic
- Do not contribute significantly to the acid-base properties
Arylamines
- Accept a proton
Secondary alkylamine
- Donate a proton
Carboxylic acid
Can act as an acid and base
Amphoteric
one can predict whether a molecule is going to be predominantly ionized or un-ionized at a given pH by knowing what
acidity/basicity of a functional group
T or F Ionized (or charged) drugs are not absorbed as efficiently as un-ionized drugs are
True
Principle for this: a weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment (small intestines)
Like dissolves like
greatly affects the routes of administration as well as absorption, distribution and elimination
Water
Potential for hydrogen bond formation
Ionization of one or more functional groups
Water solubility of a molecule
Acceptance of a hydrogen bond
increases the hydrophilic (water-loving) nature of the molecule
groups that cannot form hydrogen bonds do not enhance hydrophilicity
contribute to the hydrophobic (water-fearing) nature of the molecule
Another type of interaction that plays an important role in determining water solubility, which occurs between either a cation and the partially negative charged atom found in a permanent dipole
Ion-dipole interaction
Ion dipole interaction occurs between either a what and a what
cation and a partially negative charged atom found in a permanent dipole
approach in predicting the water solubility of molecules based on the carbon-solubilizing potential of several functional groups.
Empiric approach
If the solubilizing potential of the functional group exceeds the total number of carbon atoms present, then the molecule is considered to be what
water soluble
Opioid analgesic that contains three functional groups that contribute to water solubility
Anileridine
If Solubilizing potential is less than the total number of carbons,
insoluble in water
Molecules that contain the same number and kinds of atoms
The same arrangement of bonds, but different three-dimensional shape arrangement of atoms in space
Stereoisomers
2 types of stereoisomers
Enantiomers and Diastereomers
Pairs of molecules for which three-dimensional arrangement of atoms represents non-superimposable mirror images.
Enantiomers
All of other stereoisomeric compounds that are not enantiomers
Compounds that contain double bonds (geometric isomers) and ring systems
Exhibit different physicochemical properties, including, but not limited to, melting point, boiling point, solubility, and chromatographic behavior
Diastereomers
Empiric approach to predicting the water solubility of molecules based on the _______________ of several functional groups.
carbon-solubilizing potential
% solubility of water solubility
1%
There drugs are not absorbed as efficiently as un-ionized drugs are.
Ionized or charged drugs
T or F weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment (small intestines)
T
Example of an alkaline environment
Small intestines
ph of stomach
1 - 3.5
pH of Colon
5.6 -7
completely donate (dissociate) or accept a proton in aqueous solution
Strong acids and bases
Act as an acid or a base, depending on the prevailing pH of the solution.
AMPHOTERIC
