1004-38-2Relevant articles and documents
Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario
Menor Salván,Bouza, Marcos,Fialho, David M.,Burcar, Bradley T.,Fernández, Facundo M.,Hud, Nicholas V.
, p. 3504 - 3510 (2020)
Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth.
Efficient self-assembly in water of long noncovalent polymers by nucleobase analogues
Cafferty, Brian J.,Gállego, Isaac,Chen, Michael C.,Farley, Katherine I.,Eritja, Ramon,Hud, Nicholas V.
supporting information, p. 2447 - 2450 (2013/03/28)
Molecular self-assembly is widely appreciated to result from a delicate balance between several noncovalent interactions and solvation effects. However, current design approaches for achieving self-assembly in water with small, synthetic molecules do not consider all aspects of the hydrophobic effect, in particular the requirement of surface areas greater than 1 nm2 for an appreciable free energy of hydration. With the concept of a minimum hydrophobic surface area in mind, we designed a system that achieves highly cooperative self-assembly in water. Two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine) are shown to form extremely long supramolecular polymer assemblies that retain water solubility. The complete absence of intermediate assemblies means that the observed equilibrium is between free monomers and supramolecular assemblies. These observations are in excellent agreement with literature values for the free energy of nucleic acid base interactions as well as the calculated free energy penalty for the exposure of hydrophobic structures in water. The results of our study have implications for the design of new self-assembling structures and hydrogel-forming molecules and may provide insights into the origin of the first RNA-like polymers.
Design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8- chloropyrimido-[4,5-b]quinolines as novel antimalarials
Joshi, Advait A.,Narkhede, Sachin S.,Viswanathan
, p. 73 - 76 (2007/10/03)
The design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8- chloropyrimido-[4,5-b]quinolines as potent antimalarials is reported. Novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were designed based on a pharmacophore developed for potent antimalarial activity using Chem-X and MOE softwares. The designed molecules were synthesized by following a novel route and were evaluated by Rane's test for blood schizonticidal activity in mice infected by Plasmodium berghei. Based on the Mean Survival Time (MST) data, of the nine compounds evaluated, three had curative potential when compared with chloroquine.
