RESUMO
Among the many prebiotic phosphorylation chemistries investigated, diamidophosphate (DAP) has shown promising potential for nucleoside phosphorylation. Herein, we show that DAP's phosphorylation capability is enhanced significantly (up to 90%) in wet-dry cycles by a range of prebiotically plausible pHs (6-10) and temperatures (up to 80 °C) in the presence of additives such as formamide, cyanamide, urea, guanidine, 2-aminoimidazole, and hydantoin. For ribonucleosides, the main products are the 2',3'-cyclic phosphates along with the corresponding 2'- and 3'-phosphates, while deoxyribonucleosides form 5'- and 3'-phosphates, the ratios of which are affected by cycles and the presence and nature of the additives. A simple change of temperature to 80 °C with additives leads to higher conversion yields (≈80-90%) with an increased level of 5'-phosphorylation (≈40-49%). This demonstration of enhancing and controlling the regioselectivity of DAP-mediated phosphorylation by a range of additives and conditions potentiates transitioning to the search for more efficient catalysts, enabling regiospecific phosphorylations and oligonucleotide formation in the same milieu and setting.
Assuntos
Nucleosídeos , Ribonucleosídeos , Fosforilação , FosfatosRESUMO
Chiral Phosphoric Acids (CPAs) are a highly versatile class of Brønsted acid organocatalysts that have witnessed a surge in their use in asymmetric synthesis in recent years. Various new protocols, including photoredox, atroposelective, and multicomponent reactions, have been developed to expand the range of applications for these catalysts. This review specifically examines the use of standalone chiral phosphoric acids as organocatalysts in asymmetric syntheses from 2018 to 2022. It is important to note that this review excludes catalytic systems that utilize a combination of metal catalysts (or metal complexes) with chiral phosphoric acids. Furthermore, this review does not cover CPA derivatives, such as N-triflyl phosphoramides, chiral disulfonimides, or newly developed imidodiphosphate-type Brønsted acids.
RESUMO
Polymerization of nucleic acids in biology utilizes 5'-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology. Herein we show that diamidophosphate (DAP), in a one-pot amidophosphorylation-hydrolysis setting converts NMPs into the corresponding NTPs via 5'-nucleoside amidophosphates (NaPs). The resulting crude mixture of NTPs are accepted by proteinaceous- and ribozyme-polymerases as substrates for nucleic acid polymerization. This phosphorylation also operates at the level of oligonucleotides enabling ribozyme-mediated ligation. This one-pot protocol for simultaneous generation of NaPs and NTPs suggests that the transition from prebiotic-phosphorylation and oligomerization to an enzymatic processive-polymerization can be more continuous than previously anticipated.
Assuntos
Nucleosídeos/química , Fosfatos/química , PolimerizaçãoRESUMO
Recent demonstrations of RNA-DNA chimeras (RDNA) enabling RNA and DNA replication, coupled with prebiotic co-synthesis of deoxyribo- and ribo-nucleotides, have resurrected the hypothesis of co-emergence of RNA and DNA. As further support, we show that diamidophosphate (DAP) with 2-aminoimidazole (amido)phosphorylates and oligomerizes deoxynucleosides to form DNA-under conditions similar to those of ribonucleosides. The pyrimidine deoxynucleoside 5'-O-amidophosphates are formed in good (≈60 %) yields. Intriguingly, the presence of pyrimidine deoxynucleos(t)ides increased the yields of purine deoxynucleotides (≈20 %). Concomitantly, oligomerization (≈18-31 %) is observed with predominantly 3',5'-phosphodiester DNA linkages, and some (<5 %) pyrophosphates. Combined with previous observations of DAP-mediated chemistries and the constructive role of RDNA chimeras, the results reported here help set the stage for systematic investigation of a systems chemistry approach of RNA-DNA coevolution.
Assuntos
DNA/química , Nucleotidases/síntese química , Estrutura Molecular , Nucleotidases/química , FosforilaçãoRESUMO
Phosphorylation of (pre)biotically relevant molecules in aqueous medium has recently been demonstrated using water-soluble diamidophosphate (DAP). Questions arise relating to the prebiotic availability of DAP and other amidophosphosphorus species on the early earth. Herein, we demonstrate that DAP and other amino-derivatives of phosphates/phosphite are generated when Fe3 P (proxy for mineral schreibersite), condensed phosphates, and reduced oxidation state phosphorus compounds, which could have been available on early earth, are exposed to aqueous ammonia solutions. DAP is shown to remain in aqueous solution under conditions where phosphate is precipitated out by divalent metals. These results show that nitrogenated analogues of phosphate and reduced phosphite species can be produced and remain in solution, overcoming the thermodynamic barrier for phosphorylation in water, increasing the possibility that abiotic phosphorylation reactions occurred in aqueous environments on early earth.
Assuntos
Planeta Terra , Fosfatos/químicaRESUMO
Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group. Their catalytic performance in representative Michael addition reactions was used in an effort to compare the electronic effects of the fluorination at the methyl group. The observed differences concerning yields and ee values cannot be attributed solely to the different steric environments; theoretical results indicate distinct interactions within the corresponding transition states. The calculated transition states show that the fluorinated catalysts have stronger N-H···O and C-H···F hydrogen bonds, while the nonfluorinated systems have C-H···π contacts. These results have shown that a variety of hydrogen-bonding interactions are important in determining the yield and selectivity of thiourea organocatalysis. These details can be further exploited in catalyst design.
RESUMO
We used our recently proposed acidity-basicity interplay (ABI) model (Chem. Sci., 2018, 9, 4402) and the Jorgensen secondary interactions hypothesis (JSIH) to rationalise the experimentally observed trends in the formation constants of doubly and triply H-bonded systems with -NHO[double bond, length as m-dash]C- and -NHN- interactions. Unlike the JSIH, the ABI interpretation can explain the trends in the complexation of amide/imide homo- and heterodimers as well as ADA-DAD clusters. We found that the strongest H-bonds play a very important role, a condition which offers an alternative to the well established JSIH to modulate the stability of these relevant systems.
RESUMO
Amides dimerise more strongly than imides despite their lower acidity. Such an unexpected result has been rationalised in terms of the Jorgensen Secondary Interactions Hypothesis (JSIH) that involves the spectator (C[double bond, length as m-dash]OS) and H-bonded (C[double bond, length as m-dash]OHB) carbonyl groups in imides. Notwithstanding the considerable body of experimental and theoretical evidence supporting the JSIH, there are some computational studies which suggest that there might be other relevant intermolecular interactions than those considered in this model. We conjectured that the spectator carbonyl moieties could disrupt the resonance-assisted hydrogen bonds in imide dimers, but our results showed that this was not the case. Intrigued by this phenomenon, we studied the self-association of a set of amides and imides via 1H-NMR, 1H-DOSY experiments, DFT calculations, QTAIM topological analyses of the electron density and IQA partitions of the electronic energy. These analyses revealed that there are indeed repulsions of the type OS···OHB in accordance with the JSIH but our data also indicate that the C[double bond, length as m-dash]OS group has an overall attraction with the interacting molecule. Instead, we found correlations between self-association strength and simple Brønsted-Lowry acid/base properties, namely, N-H acidities and C[double bond, length as m-dash]O basicities. The results in CDCl3 and CCl4 indicate that imides dimerise less strongly than structurally related amides because of the lower basicity of their carbonyl fragments, a frequently overlooked aspect in the study of H-bonding. Overall, the model proposed herein could provide important insights in diverse areas of supramolecular chemistry such as the study of multiple hydrogen-bonded adducts which involve amide or imide functional groups.