Passage
Malaria is caused by the parasite Plasmodium falciparum and is transmitted through a female mosquito bite. Although there are antimalarial treatments available, P. falciparum has become resistant to many of these drugs. P. falciparum cells contain a respiratory organelle called the apicoplast that is necessary for the parasite's survival but is not found in humans. Therefore, a new drug that targets this organelle could be useful in the treatment of malaria.A portion of the apicoplast protein ferredoxin (PfFd) is shown in Figure 1, with certain amino acid residues labeled. In the apicoplast, ferredoxin NADP⁺ reductase (PfFNR) interacts electrostatically with PfFd and catalyzes an electron transfer reaction. A compound that selectively inhibits this interaction could be a beneficial antimalarial agent.
Figure 1 Structure of a portion of PfFdChalcone (Compound 3) is a compound that interacts with PfFd and exhibits antimalarial properties. A series of chalcone derivatives (Compounds 4-8) were synthesized via the aldol condensation shown in Scheme 1, where nucleophilic addition of Compound 1 to Compound 2 is followed by elimination to yield α,β-unsaturated carbonyl molecules, Compounds 3-8.
Scheme 1An inhibition assay was performed to compare chalcone (Compound 3) and its derivatives by determining the extent to which these compounds inhibited electron transfer between PfFNR and PfFd (Table 1) .Table 1 Inhibition of electron transfer assay results
Adapted from H. Suwito et al. "Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents." Molecules. ©2014 MDPI.
-What is the most likely explanation why an amino group was chosen as a substituent on the chalcone derivatives?

Question

Passage
Malaria is caused by the parasite Plasmodium falciparum and is transmitted through a female mosquito bite. Although there are antimalarial treatments available, P. falciparum has become resistant to many of these drugs. P. falciparum cells contain a respiratory organelle called the apicoplast that is necessary for the parasite's survival but is not found in humans. Therefore, a new drug that targets this organelle could be useful in the treatment of malaria.A portion of the apicoplast protein ferredoxin (PfFd) is shown in Figure 1, with certain amino acid residues labeled. In the apicoplast, ferredoxin NADP⁺ reductase (PfFNR) interacts electrostatically with PfFd and catalyzes an electron transfer reaction. A compound that selectively inhibits this interaction could be a beneficial antimalarial agent.

Figure 1 Structure of a portion of PfFdChalcone (Compound 3) is a compound that interacts with PfFd and exhibits antimalarial properties. A series of chalcone derivatives (Compounds 4-8) were synthesized via the aldol condensation shown in Scheme 1, where nucleophilic addition of Compound 1 to Compound 2 is followed by elimination to yield α,β-unsaturated carbonyl molecules, Compounds 3-8.

Scheme 1An inhibition assay was performed to compare chalcone (Compound 3) and its derivatives by determining the extent to which these compounds inhibited electron transfer between PfFNR and PfFd (Table 1) .Table 1 Inhibition of electron transfer assay results

Adapted from H. Suwito et al. "Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin - ferredoxin-NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents." Molecules. ©2014 MDPI.
-What is the most likely explanation why an amino group was chosen as a substituent on the chalcone derivatives?

Quizplus · Accepted Answer

11ecba2d_12a3_9e09_a3bf_dfe7b6cb14e1_MD0008_00 Basic and acidic functional groups can experience electrostatic interactions due to the positive-negative charge attraction. The passage states that the protein PfFd has an electrostatic interaction with PfFNR in the apicoplast, which is required for the parasite's (P. falciparum) survival. Figure 1 shows negatively charged acidic amino acid residues on PfFd, so positively charged basic amino acid residues of PfFNR most likely interact with the acidic residues in PfFd. According to the passage, chalcone (Compound 3) exhibits antimalarial properties. Chalcone derivatives (Compounds 4-7) were synthesized in an effort to create a more active antimalarial compound. The amino group is basic and will be fully protonated under physiological conditions. The resulting positive charge likely allows the chalcone derivative to interact with the acidic residues of PfFd, blocking the basic amino acid residues of PfFNR from interacting. Therefore, the amino group was most likely chosen to reduce the PfFd-PfFNR electrostatic interaction. (Choice A) An amine is a basic functional group and therefore would increase the basicity rather than the acidity of the chalcone derivatives. (Choice B) Although amino groups attached to aromatic rings are typically stable, the passage does not indicate whether the substituents on the chalcone derivatives affected the compound's overall stability. (Choice D) The lone pair of electrons on nitrogen creates a large dipole, pulling electrons toward the nitrogen and away from the carbon. Therefore, the amino group increases the polarity of the compound. Educational objective: Compounds with basic and acidic functional groups, such as amino acids with basic and acidic side chains, can form electrostatic interactions with each other due to positive-negative charge attraction of the respective functional groups. These interactions can be disrupted by other charged molecules that compete for binding.

Passage Malaria Is Caused by the Parasite Plasmodium Falciparum and Is