Noncovalent Helicene Structure between Nucleic Acids and Cyanuric Acid

Abstract

Cyanuric acid (CA), at riazine heterocycle, is extensively utilized for noncovalent self-assembly.T he association between poly(adenine) and CA into micron-length fibers was ar emarkable observation made by Sleiman and coworkers, who proposed that adenine and CA adopt ah exameric rosette configuration in analogy with previously reported structuresf or CA assemblies. However, recent experimental observations from the Krishnamurthyg roup led to a reevaluationo ft he hexameric rosette model,w herein they have proposed ah ydrogen-bonded helicene model as an alternative. Our molecular dynamics simulations show that the hexad model is indeed unlikely and that this novel noncovalent helicene geometry,w here the adenine and CA bases form an extended helical hydrogen-bond network across the system,i samore probable structural motif. The existence of noncovalent helicene compounds may have wide-ranging applicationsi nD NA nanotechnology and helicene chemistry.

The Unexpected Base‐Pairing Behavior of Cyanuric Acid in RNA and Ribose versus Cyanuric Acid Induced Helicene Assembly of Nucleic Acids: Implications for the Pre‐RNA Paradigm

“…[21] To understand the details of the differences between the hexad rosette model and the helicene model,w ei nitiated col- laborativei ns ilico molecular dynamics simulations led by the Sherrillg roup.T he results of this investigation are described and discussed, in detail, in an accompanying paper. [7] Briefly, the simulations show that the triazine-purine hexad rosette structure is unstablea nd readily,a nd, naturally,t ends toward the helicene model,i nw hich the base pairs are out of plane, as predicted by the ChemDraw figuresa nd molecularm odels ( Figure 5). The simulations also show that the helicene dyad model can accommodate the RNA (or DNA) strandsw ith minimal deviationf rom the canonical A-form conformation,w ith the helicene-helicene model similarly adopting the A-form conformation, but with ag reater deviation.…”

“…The simulations also show that the helicene dyad model can accommodate the RNA (or DNA) strandsw ith minimal deviationf rom the canonical A-form conformation,w ith the helicene-helicene model similarly adopting the A-form conformation, but with ag reater deviation. [7] Substituting CARC insteado fC Aw as confirmed to destabilize the assembly due to steric hindrance between CARC and the RNA backbone. [7] The observation that CA is able to mediate supramolecular assemblies, as opposed to CARC or CA ONs shows that ah eterocycle may not function in exactly the same way if it is incorporated into ab ackbone.…”

“…[7] Substituting CARC insteado fC Aw as confirmed to destabilize the assembly due to steric hindrance between CARC and the RNA backbone. [7] The observation that CA is able to mediate supramolecular assemblies, as opposed to CARC or CA ONs shows that ah eterocycle may not function in exactly the same way if it is incorporated into ab ackbone. This reveals al imitation of extrapolating the base-pairingb ehavior all the way from am onomer to the supramolecular assembly.T he fact that the CA-RNA oligomer is compromised in base pairing, in the conventional oligomeric pre-RNAt oo ligomeric RNA scenario, [22] would be considered problematic because the CA-RNAo ligomer would be hampered in function and, importantly,i nb ase-pair-mediated information transfer to its successor.I ti sw ellk nownt hat the nature of the backbone can affect the base-pairing properties of the heterocycles.…”

“…[4] Further support for the helicene structure was obtained by Sherrill and co-workers, through in silico molecular dynamic simulations, the details of which are reported in the accompanying paper. [7] Finally, we CA building block andits self-assemblies. Proposed hexad structure of CA derivatives with A) TAP [2a,b] and B) adenosine-5'-monophosphate (AMP) [5] and poly(A).…”

Using transient equilibria (TREQ) to measure the thermodynamics of slowly assembling supramolecular systems

“…A cross section of the proposed structure ( Fig. 1 ) shows the deoxy adenosine (dA) of three different DNA strands hydrogen bonding to CA molecules in a continuous supramolecular helicene ( 30 , 31 ). We note that the ideal helicene structure has a 1:1 ratio of dA residues and CA molecules.…”