PHA4011-E Unit 1: Fundamental Chemistry of Drugs and Molecules of Life Flashcards

Flashcards reviewing key concepts of organic chemistry, drug structures, macromolecular building blocks, stereochemistry, and drug design from Unit 1.

Who is the Unit Lead for PHA4011-E Fundamentals of Pharmacy Science Unit 1?

Dr Sriharsha KANTAMNENI

In a skeletal formula of an organic molecule, what do the line ends and vertices represent?

Carbon atoms

What structural features are indicated by the annotations on this skeletal structure of Aspirin?

Vertices and line ends represent carbon atoms, atoms other than carbon and hydrogen (heteroatoms) are always shown, and hydrogen atoms bonded to heteroatoms are explicitly shown.

What three sequential components comprise the systematic IUPAC name of an organic compound?

Prefix, Parent, and Suffix

According to IUPAC rules, how is the molecule with a 6-carbon chain containing an aldehyde at carbon 1 and a hydroxyl group at carbon 4 systematically named?

4-hydroxyhexanal

How is the $\text{p}K_a$ of a functional group defined?

The pH at which the ionisation of the functional group is exactly $50|\text{\%}$.

What is the typical $\text{p}K_a$ range for a carboxyl functional group ($\text{R-COOH}$) in drug substances?

$\text{p}K_a$ $2-4$

What is the typical $\text{p}K_a$ value for a pyridine ring in drug substances?

\text{p}K_a \text{\~} 5.5

What atomic hybridisation and geometry correspond to a carbon atom forming $4$ $σ$-bonds?

$sp^3$ hybridisation with tetrahedral geometry and bond angles of $109^\circ 28'$

What is the $\text{H-O-H}$ bond angle in water, and why is it compressed compared to an ideal tetrahedral angle?

The bond angle is $104.5^\circ$; it is compressed because the two unshared lone pairs on oxygen exert stronger repulsion than the bonding electron pairs.

How do the physiological effects of the $(R)$ and $(S)$ enantiomers of thalidomide differ?

The $(S)$ enantiomer produces the desired sedative effect, whereas the $(R)$ enantiomer causes birth defects (such as limb malformation) by inhibiting blood vessel growth.

What is the relative order of electronegativity for key elements common in drug structures?

$$\text{F} > \text{O} > \text{Cl}, \text{N} > \text{Br} > \text{C}, \text{I}, \text{S} > \text{P} > \text{H}$$

What is the normal distance range between heavy atoms involved in a biological hydrogen bond?

$2.2-4.0\,\text{\AA}$ (with a typical heavy atom distance of $3.5\,\text{\AA}$)

Why is arginine considered an essential amino acid in human diets despite the body's ability to synthesize it?

The majority of synthesized arginine is consumed in the urea cycle to produce urea, leaving insufficient amounts for protein synthesis during growth in infants and children.

What is a zwitterion in the context of amino acid acid-base chemistry at physiological pH?

A species containing both a negatively charged carboxylate group ($\text{-COO}^-$) and a positively charged ammonium group ($\text{-NH}_3^+$), resulting in a net charge of zero.

In a protein $\alpha$-helix, between which groups do hydrogen bonds form, and how many amino acid residues are present per turn?

Hydrogen bonds form between the carbonyl oxygen of one residue and the amide $\text{NH}$ hydrogen of the residue $4$ places down the strand, with $3.6$ residues per turn.

What molecular change in hemoglobin causes red blood cell sickling in sickle cell anaemia?

A single amino acid substitution in the primary sequence of hemoglobin (forming HgbS), which alters its structure and promotes bending and rigidity under low oxygen tension.

Why are sugars such as sucrose and mannitol added to protein solutions prior to freeze-drying?

They act as cryoprotective agents by repelling hydrophobic amino acid residues to prevent denaturation, serve as bulking agents, and enhance cake appearance.

Which liver enzyme activates the prodrug clopidogrel into its active metabolite R-130964?

CYP2C19

How do the physical and pharmaceutical properties of $\alpha$--lactose and $\beta$--lactose differ?

$\beta$--lactose is twice as sweet as $\alpha$--lactose, but $\alpha$--lactose possesses superior powder-flow properties, making it preferred as a tablet excipient.

What is the biochemical mechanism of action of atorvastatin (Lipitor)?

It is a potent competitive inhibitor of HMG-CoA reductase, inhibiting the production of mevalonic acid to decrease downstream cholesterol synthesis.

What is the active co-enzyme form of Vitamin $B_1$ (Thiamin), and what disease is caused by its deficiency?

Thiamin diphosphate (thiamin pyrophosphate or TPP); deficiency causes Beriberi.

What major fetal developmental defect is prevented by taking folic acid (Vitamin $B_9$) during pregnancy?

Neural tube defects, such as spina bifida.

What stomach-derived protein is required for Vitamin $B_{12}$ absorption, and what condition results from its autoimmune destruction?

Intrinsic factor; its destruction causes pernicious anaemia.

Why is the risk of Vitamin A toxicity lower when consuming plant-derived $\beta$-carotene than animal-derived retinyl esters?

The intestinal conversion of $\beta$-carotene to active retinol is adaptive and inversely regulated relative to intake levels.

How does the anticoagulant drug warfarin interfere with Vitamin K activity?

Warfarin inhibits Vitamin K epoxide reductase, blocking the recycling of oxidized Vitamin K back to its active reduced form required for $\gamma$-glutamyl carboxylase.

What four parameters define Lipinski's Rule of Five for oral drug-likeness?

1) No more than $5$ hydrogen bond donors; 2) No more than $10$ hydrogen bond acceptors; 3) Relative molecular mass less than $500$; 4) Octanol-water partition coefficient $\log P$ not greater than $5$.

What are the estimated average timeline and cost required to bring a single new drug to market?

More than $10$ years and over $\$1\,\text{billion}$.

Which surface enzyme of the influenza virus is targeted by zanamivir and oseltamivir to prevent viral escape from host cells?

Neuraminidase (sialidase)

What structural modifications were made to zanamivir to produce the orally active drug oseltamivir?

Polar groups were removed and replaced with hydrophobic side chains to lower polarity and molecular weight according to Lipinski's rules, and the drug was formulated as an ethyl ester prodrug.