The Role of Aromatic Substitution on 1,4-Dihydropyridine Binding
Part 2: Comparison of Aromatic Substitution Sites
Shown below are four
chemically similar dihydropyridines: desnitro-nifedipine (upper-left corner), nifedipine (upper-right corner), a meta-analog of nifedipine (bottom-left corner), and a para-analog
of nifedipine (bottom-right corner).
To help you answer this
question, you may wish to rotate and examine individual structures. In
order to do this, use the following guidelines:
- The on-screen trackball rotation as well as the right
and bottom rotation bars will simultaneously rotate all four compounds
(not a very useful process!) unless one of the compounds is
selected.
- To select a specific compound, click on the “Select”
arrow and then click on any atom within the molecule. If you are
successful, the atom will turn yellow. Click the “Rotate” button, HOLD DOWN THE SHIFT KEY, place
your mouse cursor near the selected molecule, and it move vertically or
horizontally to rotate your chosen compound.
- To change compounds, simply repeat the previous step,
and click on an atom of the desired compound.
- If you wish to view rotations similar to that
previously done with the aromatic ring of desnitro-nifedipine,
follow these steps: (1) Change the model display to "Ball
and Stick", (2) Select the bond connecting the 1,4-DHP
ring to the aromatic ring (you may want to use the “Zoom”
function to select the bond). For nifedipine,
this is the bond between C[57]-C[58], for the meta-analog, it is
the bond between C[16]-C[17], and for the para-analog,
it is the bond between C[143]-C[144]; (3) Change the model display back to
"Space Filling", (4) Select the “Rotate” button, (5)
Simultaneously, hold down BOTH
the “Shift” and “B” keys, and (5) move the
mouse cursor vertically (up and down) to rotate. You can then repeat
for any additional structures.
- If you are having difficulty seeing the interaction
between the aromatic ring and the ester oxygen atoms, simply use the “Zoom”
function (they will all enlarge). This may put a portion of the
molecule "off-screen", but will still allow you to see the
important interaction.
- Remember, you can always reload/refresh the page to
start over if you need to do so!!
Question 4
If nifedipine
and its meta- and para-analogs
were all substituted with chloro groups instead of nitro groups (everything else
remaining the same), would your answer for question 3 change? Why or why
not?
Navigation
Intro / Question 1
/ Question
2 / Questions 3&4
Return to Main Index
This site
was developed and is maintained by Dr. Marc W. Harrold (harrold@duq.edu)
Copyright, September 2001, Revised 9/18/07.