Penicillin acid stability (TPR Ochem Passage #29)

ModerateMouse

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May 5, 2010
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    EDIT: I posted in the wrong forum! Can someone please move it to MCAT Study Material? :) )

    Hello,

    This is the basic structure of penicillin.

    penicillin-core.png

    Penicillin_core.svg
    The 'R' group is variable.

    Some penicillins are more acid stable, and some are less.

    The acid-unstable penicillins are hydrolyzed at the amide bond between the 'R' group and the other half of the molecule.

    Some side groups make penicillin more acid resistant than others.

    This is explained (search for 'decreases the electron density of the side chain') by the idea that electron withdrawing side groups remove electron density from the carbonyl, making it less likely to be protonated by the acid. This protonation begins the acid hydrolysis.

    TPR has a question (4) that asks why the amide bond in dicloxacillin and nafcillin is stable at low pH.

    The answer is:

    "amide bonds do not easily undergo hydrolysis"

    because

    "amides are stabilized by the ability of the nitrogen lone pair to donate electron density to the electrophilic carbonyl carbon. Amides do not easily undergo hydrolysis"

    Does this make sense? Because there is an amide bond in all penicillins, not just in dicloxacillin and nafcillin. Wouldn't that make them all equally acid stable then?

    Seems like their reasons would work only if some penicillins didn't have an amide bond between the R group and the 6-APA (other half).
     

    PiBond

    Call me Bond...PiBond
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    Aug 12, 2009
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      EDIT: I posted in the wrong forum! Can someone please move it to MCAT Study Material? :) )

      Hello,

      This is the basic structure of penicillin.

      penicillin-core.png

      Penicillin_core.svg
      The 'R' group is variable.

      Some penicillins are more acid stable, and some are less.

      The acid-unstable penicillins are hydrolyzed at the amide bond between the 'R' group and the other half of the molecule.

      Some side groups make penicillin more acid resistant than others.

      This is explained (search for 'decreases the electron density of the side chain') by the idea that electron withdrawing side groups remove electron density from the carbonyl, making it less likely to be protonated by the acid. This protonation begins the acid hydrolysis.

      TPR has a question (4) that asks why the amide bond in dicloxacillin and nafcillin is stable at low pH.

      The answer is:

      "amide bonds do not easily undergo hydrolysis"

      because

      "amides are stabilized by the ability of the nitrogen lone pair to donate electron density to the electrophilic carbonyl carbon. Amides do not easily undergo hydrolysis"

      Does this make sense?
      Because there is an amide bond in all penicillins, not just in dicloxacillin and nafcillin. Wouldn't that make them all equally acid stable then?

      Seems like their reasons would work only if some penicillins didn't have an amide bond between the R group and the 6-APA (other half).

      The questions is essentially asking "what is the reason an amide bond is stable". Answers A, B, and D make no sense. Thus we are left we answer C (amide bonds do not easily undergo hydrolysis). This is a true statement considering that the nitrogen lone pair can donate in and forms the partial double-bond character that we also observe in peptide bonds. Also, consider the fact that the an NH2 as leaving group is terrible, and thus this carboxylic acid derivative is the least reactive.

      There is no part of the question that is asking us to compare the relative stabilities of dicloxacillin/nafcillin and other penicillins. Therefore, we shouldn't be digging around for outside material that doesn't pertain to the questions.

      hope that helps
       
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