In 1972, Georges Ungar reported the discovery of a peptide that appeared to transfer learning. Ungar's claim was based on experiments in which rats placed in a chamber with specially designed dark and light regions were trained to avoid the dark regions of the chamber. Following their training, the rats were killed and brain extracts were prepared. These brain extracts were injected into naive rats which were then observed to acquire the fear of darkness without training. Two hypotheses were proposed to explain these remarkable results:Hypothesis 1Ungar concluded that the extracts contained some chemical that transmitted the learned fear of darkness to the naive rats. A fifteen amino-acid polypeptide was isolated from the brain extracts and sequenced. Ungar claimed that this peptide, called scotophobin, was a chemical transmitter of learning. The peptide had the primary structure shown below: C-ser-asp-asn-arg-gln-gln-gly-lys-ser-ala-arg-gln-glygly-tyr-NscotophobinHypothesis 2Other researchers, who tested scotophobin but could not reproduce Ungar's results, argued that scotophobin did not transfer the learned fear of darkness. Instead, they suggested that scotophobin, which is structurally similar to ACTH and vasopressin, acted to increase stress in the rats. Since stress increases sympathetic nervous activity, rats injected with scotophobin would become hyperactive and tend to spend less time in the dark regions of the experimental chamber. They argued that such stress responses in the rats could be misinterpreted as a fear of darkness. Ungar's claim was further weakened by chemical analysis in which both the scotophobin extracts which Ungar had injected into the naive rats and a sample of synthesized scotophobin peptide were subjected to SDS polyacrylamide gel electrophoresis, as shown in Figure 1.Figure 1The chemical analysis of Ungar's extract most likely weakened his claim that scotophobin transferred the learned fear of darkness because it showed that:
Answer(s): A
The electrophoresis of Ungar's extract shows that multiple compounds were present. This weakens the argument that scotophobin alone is responsible for the apparent transfer of learning.Choice B is incorrect because the extract does have a band at a similar displacement as that of the synthetic scotophobin indicating that scotophobin is present.Choice C is incorrect because the passage never discusses the concentration requirements for scotophobin to elicit a response. Electrophoresis is useful for identifying the proteins in a mixture, but it is not as useful for calculating concentrations. This information cannot be concluded from the data.Choice D is incorrect because the electrophoretic data does not provide information about the structure of the other proteins in the extract.
Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function.Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin. Meperidine(demerol)Figure 2One of the requirements of the "morphine rule" is that an aromatic ring be attached to a quaternary carbon in order for the molecule to be biologically active. The quaternary carbon of any morphine-like substance must be:I). a stereocenterII). sp3 hybridizedIII). sp2 hybridized
Answer(s): B
A quaternary carbon is bonded to four alkyl groups. Any carbon that forms four bonds adopts the tetrahedral configuration and must be sp3 hybridized. sp3 hybridization occurs when one s orbital and three p orbitals mix to form four equivalent hybrid orbitals capable of forming four bonds.Choices A and C are incorrect because a quaternary carbon (bonded to 4 alkyl groups) need not be a chiral center if two of these alkyl groups are identical. This is shown below: Choice D is incorrect because an sp2 hybridized carbon adopts a planar configuration and can only bind to three substituents (not the four required of a quaternary carbon).
Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function.Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin. Meperidine(demerol)Figure 2How many chiral carbons are there in morphine?
Any carbon bonded to four different substituents will be chiral. Morphine has five such carbons as shown below:Note that the nitrogen atom is also a chiral center. If nitrogen's lone pair of electrons is considered a fourth substituent bonded to nitrogen, it can be seen that nitrogen can also act as a chiral center. Some amines can invert configuration (and thus are not chiral). The tertiary amine of morphine cannot invert it is locked into its configuration by the ring structure. However, the question asks for the number of chiral carbons, not the number of chiral centers.
Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function.Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin. Meperidine(demerol)Figure 2Which of the following compounds would be most likely to have morphine-like biological effects?
Answer(s): D
The passage states that there are certain requirements, the "morphine rules," that give a compound morphine- like biological activity. These requirements are an aromatic ring attached to a quaternary carbon and a tertiary amine situated two carbons away from that quaternary carbon. A quaternary carbon is a carbon bonded to four alkyl groups. A tertiary amine is bonded to three alkyl groups. The only structure that meets these requirements is structure D. The other answer choices look like the structures in the passage but do not meet all of the "morphine rules". Note that if the written description of the "morphine rules" is not clear enough, you can look at the figures in the passage as well.Choice A is incorrect because the aromatic ring is not attached to a quaternary carbon. It is attached to two secondary carbons.Choice B is incorrect because it lacks a tertiary amine. It has a secondary amine bonded to only 2 alkyl groups.Choice C is incorrect because the tertiary amine is not located two carbons away from the quaternary carbon. It is only one carbon away from the quaternary carbon.
Morphine alkaloids derived from the opium poppy have long been used as analgesics. Codeine, the methyl ether of morphine, is a naturally occurring alkaloid with medicinal properties very similar to those of morphine. Thousands of derivatives of morphine have been synthesized and tested for their biological effects. For example, the diacylated derivative of morphine, heroin, is a highly addictive drug. Much effort has gone into understanding how morphine and its derivatives function.Studies have shown that certain common structural features of alkaloids are required for the compound to exhibit biological activity. These structural requirements are summarized by the so called "morphine rule":Demerol and methadone, shown in Figure 2, are two synthetic alkaloids designed to satisfy the "morphine rule." Synthetic alkaloids such as these have been found to mimic certain physiological properties of morphine and its derivatives, and have found pharmacological application due to other, more desirable biological effects. Methadone has been used widely in the United States and Great Britain as a treatment for heroin addiction; it reduces the physical symptoms accompanying withdrawal without producing many of the other effects of heroin. Meperidine(demerol)Figure 2Morphine can be reacted with 2 equivalents of ethanoyl chloride (acetyl chloride) to form heroin. In this reaction, the hydroxy groups of morphine function as:
This reaction proceeds through nucleophilic attack by the hydroxy oxygen (of morphine) on the electrophilic carbonyl carbon of ethanoyl chloride. A nucleophile is an electron rich (Lewis Base) species that can attack an electrophile (electron poor species).Thus, the hydroxy groups on morphine act as nucleophiles.Choice B is incorrect because the carbonyl carbon is the electrophile in this reaction. The carbonyl group is polarized. Electrons are drawn towards the electronegative oxygen leaving the carbon with a slightly positive charge. Thus, the carbon is electron deficient and "wants" electrons. It is an electrophile.Choice C is incorrect because chloride acts as the leaving group in this reaction.Choice D is incorrect because Lewis acids are electron pair acceptors. The hydroxy group acts as an electron pair donor, a Lewis base.
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