THE REACTIVITY OF NITROGEN HETEROCYCLES IN COMPLEX PREBIOTIC MIXTURES: USING CHEMICAL TRENDS TO EVALUATE PLAUSIBLE STRUCTURES OF PRIMITIVE GENETIC MATERIAL ON EARLY EARTH
Open Access
- Author:
- Rodriguez, Laura Elise
- Graduate Program:
- Geosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- November 01, 2018
- Committee Members:
- Christopher Howard House, Dissertation Advisor/Co-Advisor
Christopher Howard House, Committee Chair/Co-Chair
Katherine Haines Freeman, Committee Member
James Kasting, Committee Member
Philip C Bevilacqua, Outside Member - Keywords:
- Astrobiology
Origins of life
Nucleobases
RNA World
Pre-RNA
Mass spectrometry
Michael addition - Abstract:
- The ability to store information is critical for the origins and evolution of life as we know it. Understanding the origin of genetic molecules relevant for abiogenies on Earth would elucidate conditions conducive for the formation of Earth-like life and the possibility of such life forming elsewhere in our universe. Unfortunately, little is known about the structures of genetic molecules relevant for the origins of life on Earth and without geochemical constraints the possibilities are endless. RNA—having the ability to catalyze reactions and store information via nitrogen heterocycles (N-heterocycles)—is widely believed to have been one of the earliest genetic and enzymatic molecules used by life. However, it remains unclear whether alternative molecules with dual genetic-enzymatic capabilities (i.e. pre-RNAs) preceded or coexisted with RNA on the early Earth. One approach to constrain the identity of relevant genetic polymers is to study the chemical evolution of N-heterocycles, the means by which all modern genetic material (RNA, DNA) stores information. In Chapter 2, we studied the reactivity of 53 N-heterocycles in Miller-Urey mixtures generated from reducing and neutral atmospheres using a combination of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Remarkably, we discovered that a wide-range of N-heterocycles develop short carbonyl side chains reminiscent of the proposed pre-RNA, peptide nucleic acid (PNA). Our results demonstrate multiple pathways for generating these carbonylated N-heterocycles, regardless of the starting atmosphere. Notably, the majority of these side chains were generated via Michael additions with organics that are widespread in our solar system. The leading theory for the origin of sugars on the early Earth is the polymerization of formaldehyde (i.e. the formose reaction). In Chapter 3, we investigated whether N-heterocycles could form sugar side chains (i.e. glycosides) with formose products. Mass spectrometry of the mixtures showed that N-heterocycles, including the biological nucleobases, spontaneously form C4-C9 sugar and sugar alcohol side chains via Michael additions. Intriguingly, this work demonstrates that the aldehyde side chains generated via Michael additions in Miller-Urey mixtures (Chapter 2) can be converted into sugar and sugar alcohols via aldol reactions; in some cases, these reactions yield a glycoside structurally similar to the proposed RNA precursor, pyranosyl-RNA (p-RNA). In this chapter we also discuss adducts with masses corresponding to sugar side chains that formed in Miller-Urey mixtures derived from neutral atmospheres (Chapter 2). Overall these results demonstrate a facile mechanism for glycosylating N-heterocycles, including the canonical nucleobases, in complex prebiotic mixtures. The coupling of genetic information with metabolism would have been a crucial step for the origins and evolution of life. While we demonstrated that the precursors to PNAs may have readily formed on early Earth in Chapter 2 and how under certain conditions these molecules can be converted to RNA-like glycosides in Chapter 3, it remains uncertain whether a genetic structure composed of these molecules would possess both genetic and catalytic properties. Given the catalytic properties of Fe-S clusters, their role in modern metabolism, and the fact that Earth’s early oceans were iron-rich with a higher influx of sulfide at hydrothermal vents, Fe and S may have been relevant to the formation of dual genetic-enzymatic molecules on early Earth. In Chapter 4 we decided to explore the plausibility of a pre-RNA composed of N-heterocycles with sulfidic side chains linked by Fe-S clusters (i.e. Fe-RNA). Specifically, we explored whether sulfide-rich formose reaction mixtures would facilitate the formation of sulfidic side chains on N-heterocycles, including thiosugars; adducts were detected using high-resolution mass spectrometry. We then tested whether thiosugars could form iron-sulfur clusters with inorganic sulfide and iron under prebiotic conditions using a combination of UV-Vis, Mössbauer, and NMR spectroscopy. Overall the work described herein elucidates robust reactions of N-heterocycles, including the biological nucleobases, and demonstrates how these molecules can readily form precursors of PNA, RNA-like molecules, and Fe-RNA in complex prebiotic mixtures. Notably, each of these genetic precursors have the same chemical origin: the Michael addition. This is particularly exciting as Michael additions are regioselective, forming side chains at positions N1 for pyrimidines, and N9 for purines, i.e., the positions where sugars attach in RNA and DNA. Moreover, these genetic precursors were formed from organics that are widespread in the solar system; thus, our results may have implications for the formation of genetic precursors on other worlds beyond Earth.