How did nature ‘invent’ DNA- the self-replicating molecules that gave rise to life on Earth? We approach the mysteries of origins of life by investigating the chemical and physical properties of the building blocks of life. A range of purines and pyrimidines distinct from the extant nucleobases (as seen in Figure 1) may have been present at the time of the earliest abiotic synthesis of nucleic acids, as nucleobase analogs have been found on meteoritic material.
Figure 1
82 alternative base pairs have been proposed to have hydrogen bonding patterns and geometries like those of the canonical base pairs. However, they vary in photostability which can be measured by excited state lifetimes. By having a shorter excited state lifetime, these molecules bypass destructive chemical processes of electronic excitation through internal conversion. The canonical base pairs have excited state lifetimes in the order of picoseconds compared to the nanoseconds timescale of alternative nucleobases as seen in figure 2. Studying these derivatives demonstrate that photochemical stability is dependent on structure. Minor structural modifications can result in significant changes in lifetimes. For example, minor differences between adenine (also called 6-aminopurine) and 2-aminopurine results in ten order of magnitude difference in the excited state lifetime.
Two of these alternative nucleobases that could have been available are isocytosine and isoguanine. These molecules have the potential to replace cytosine and guanine as a base pair in DNA due to the fact that they pair similar to the GC pair, yet guanine and cytosine still prevailed as two of the five canonical base pairs. To better understand why GC won in the biological race over isoG-isoC, a variety of photochemical studies have been performed to probe many properties of these compounds. Through this effort, it has been found that isocytosine has a similar excited state lifetime to its counterpart, guanine. However, isoguanine has been found to have a much longer lived excited state than cytosine in the tautomeric form that would form Watson-Crick base pairing. After discovering and documenting the gas phase spectroscopy of the individual bases in various tautomeric forms, we have investigated their H-bonded binary clusters with each other (both homo- and hetero-diners) and their clusters with one and two water molecules. We have determined structures and obtained structure selective vibrational frequencies from IR-UV double resonance spectroscopy.
Combined with computational studies from collaborators, our group studies these various photochemical pathways alternative nucleobases can undergo in the gas phase in order to study the intrinsic photoproperties. Our group have investigated nucleobase derivatives such as isoguanine, isocytosine, and 6-thioguanine. We are currently interested in exploring hypoxanthine and 8 oxo-purine using our laser desorption, jet-cooling coupled with resonance enhanced multi-photon ionization (REMPI) technique.
