Eric S. Handberg and Dr. David V. Dearden, Chemistry and Biochemistry
Introduction
Host exchange experiments (see Figure 1) compare the fit of left-handed molecules (L-) and right-handed molecules (D-) in a host. Molecules that possess this “handedness” property are said to be chiral. In chiral crown ether host exchange experiments, chiral crown ethers distinguish the fit of D-phenylalanine (Phe), D-tyrosine (Tyr), D-tryptophan (Trp), D-histadine (His), and D-aspartic acid (Asp) apart from L-Phe, L-Tyr, L-Trp , L-His, and L-Asp by forming chemically distinct complexes between the chiral host and the left- and right-handed amino acids1-3. Because the L- and D-handed molecules have different physical properties, the rate constants for exchange reactions differ. The condition when the rate constants for L- and Dhanded molecules do not match is called chiral discrimination4-6. The ability of the host to discriminate between L- and D-handed molecular guests is measured via the rate constants. Identical rate constants for L- and D-molecules in a host-guest reaction indicate a nondiscriminating host, and different rate constants indicate a host with good discriminating ability.
Usually, achiral molecules cannot discriminate. Despite the achiral nature of 18-crown-6 (18C6) and dibenzo-30-crown-10 (DB30C10), these achiral hosts might still be good discriminators. If 18C6 and DB30C10 are floppy enough to wrap around the amino acids forming a low-energy structure with a temporary chiral center, then the crown complexes of L- and D- amino acids will form chemically distinct complexes when they interact with an attacking chiral amine. Thus an achiral host could induce chiral discrimination.
The hypothesis was tested by measuring the rate constants of D- and L- handed versions of Phe, Tyr, Trp, His, and Asp when a more basic chiral amine replaced the amino acid in an achiral crown/chiral amino acid complex. The hypothesis would be correct if the D- and L-rate constants were different.
Procedures
D- and L-Phe, Trp, and Tyr rate constants were measured using a Bruker Apex Fourier transform ion cyclotron resonance mass spectrometer. Reactants were introduced into the ion trap by electrospraying a 10-4 M solution of 18C6 or DB30C10 and one amino acid enantiomer and by leaking the amine through a variable leak valve. Exchange reactants were as follows: chiral methylbenzylamine (MBA) with Phe and with 18C6, chiral naphthylethylamine (NapEt) was used with 18C6 and with Tyr and Trp, and DB30C10 was used with Phe, Trp, His, and Asp.
Results
If our hypothesis were correct then the hypothesis would have to work with DB30C10 because DB30C10 is the floppiest crown and would show chiral induction if any crown could. Our hypothesis failed; the rate constants for the L- and D-guests were the same within the margins of error.
Conclusion
The achiral 18C6 fails to induce chiral discrimination. These results were presented as a poster at the American Society of Mass Spectrometry conference and at the XXV International Symposium on Macrocyclic Chemistry7.
References
- Dearden, D. V.; Dejsupa, C.; Liang, Y.; Bradshaw, J. S.; Izatt, R. M. J. Am. Chem. Soc. 1997, 119, 353-359.
- Ramirez, J.; He, F.; Lebrilla, C. B. J. Am. Chem. Soc. 1998, 120, 7387-7388. 3.Sawada, M.; Takai, Y.; Yamada, H.; Kaneda, T.; Hirose, K.; Okumura, Y.; Misumi, S. Org. Mass Spectrom. 1993, 28, 1525-1528.
- Sawada, M.; Shizuma, M.; Takai, Y.; Yamada, H.; Kaneda, T.; Hanafusa, T. J. Am. Chem. Soc. 1992, 114, 4405-4406.
- Sawada, M.; Shizuma, M.; Takai, Y.; Yamada, H.; Kaneda, T.; Hanafusa, T.; Nishida, J.; Arakawa, R.; Okamoto, M.; Hirose, K.; Tanaka, T.; Naemura, K. J. Chem. Soc., Perkin Trans 2 1998, 701-710.
- Liang, Y.; Bradshaw, J. S.; Izatt, R. M.; Dearden, D. V.; Pope, R. M. Int. J. Mass Spectrom. 1999, 185/186/187, 977-988.
- I give thanks to David V. Dearden, Katherine A. Kellersberger, Sarah N. Ward, and Joseph Anderson for technical assistance, and the BYU ORCA office for financial support.