A chemical labeling of N6-formyl adenosine（f6A） RNA

N⁶-methyl adenosine（m⁶A） is an eminent epigenetic mark in m RNAs that affects a broad range of biological functions in diverse species. However, the chemically inert methyl group prevents a direct labeling of this modification for subsequent detection and sequencing. Therefore, most current approaches for the labeling of m⁶A still have limitations of relying on the utilization of corresponding methyltransferases,which resulted in the lacking of efficiency. Here w...     

Identification of Flavin Mononucleotide as a Cell‐Active Artificial N6‐Methyladenosine RNA Demethylase

N⁶‐Methyladenosine (m⁶A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m⁶A residues in mRNA. Herein, the first identification of a small‐molecule modulator that functions as an artificial m⁶A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m⁶A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m⁶A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.     

Chemical Deprenylation of N6-Isopentenyladenosine (i6A) RNA

N⁶-isopentenyladenosine (i⁶A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i⁶A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i⁶A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i⁶A.     

Chemical Deprenylation of N6‐Isopentenyladenosine (i6A) RNA

N⁶‐isopentenyladenosine (i⁶A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i⁶A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i⁶A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i⁶A.     

Improved Synthesis of Phosphoramidite-Protected N6-Methyladenosine via BOP-Mediated SNAr Reaction

N⁶-methyladenosine(m⁶A) is the most abundant modification in mRNA. Studies on proteins that introduce and bind m⁶A require the efficient synthesis of oligonucleotides containing m⁶A. We report an improved five-step synthesis of the m⁶A phosphoramidite starting from inosine, utilising a 1-H-benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)_-mediated S_NAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.     

N 6-Hydroperoxymethyladenosine: a new intermediate of chemical oxidation of N6-methyladenosine mediated by bicarbonate-activated hydrogen peroxide

N ⁶-Methyladenosine (m⁶A) represents a relatively abundant modification in eukaryotic RNA. Because m⁶A has similar properties to adenosine and a low reactivity, limited research has been focused on this nucleoside. In this study, we revealed an important intermediate in the oxidation of m⁶A through the bicarbonate-activated peroxide system. Over the course of oxidation, we found a new mechanism in which N⁶-hydroxymethyladenosine (hm⁶A), N⁶-formyladenosine (f⁶A) and N⁶-hydroperoxymethyladenosine (oxm⁶A) were intermediate products, and adenosine was the final product. In this study, oxm⁶A was isolated using HPLC and characterized by mass spectrometry, NMR and diphenyl-1-pyrenylphosphine (DPPP) fluorescence detection. This study provides a new modified nucleoside and demonstrates oxidative demethylation of m⁶A by reactive oxygen species at the nucleobase level and in RNA strands.     

RNA Methylation m6A: A New Code and Drug Target?

The m⁶A‐RNA modification is a dynamic and reversible process, which has emerged as a new RNA code for the regulation of gene expression. The functional network of methyltransferases (writers), demethylases (erasers), and binding proteins (readers) modulate the level of m⁶A modification. Dysfunction of RNA methylation has been associated with various fundamental biological processes and human diseases. Herein, we briefly introduce an understanding‐enabled manipulation on m⁶A‐RNA modification with an emphasis on the use of small‐molecule intervention.      

Catechol reactivity: Synthesis of dopamine derivatives substituted at the 6-position

Dopamine is a ubiquitous neurotransmitter essential in the proper functioning of the human body. In addition to this critical role, the catecholamine core has shown utility as a scaffold for numerous drugs and in other applications, like metal detection and adhesive materials. Substituents at the 6-position of dopamine’s catechol core can modulate its stereoelectronic properties, the acidity of its phenolic hydroxyl groups, and the overall hydrophobicity of the molecule. Herein, we report the synthesis of a series of four novel dopamine analogues substituted at the 6-position of catechol core. The ¹H NMR chemical shift of the aromatic proton meta to the substituent correlated strongly with the Hammett σ_m constant, confirming the electronic properties of substituents.     

Crystalline texture of injection-molded nylon 6

Injection-molded specimens of nylon 6 were examined by x-ray diffraction as a function of depth in three characteristic directions. A skin and a core were always found to be present which differed in the degree of crystalline perfection and crystal modification. While the core of pure nylon 6 was found to be not oriented, the core of specimens containing nucleating agents was found to contain a typical texture of the monoclinic modification of nylon 6 in which the distribution probability of the a^* and c^* axes resembles ellipsoids with three unequal axes. A model explaining this texture as due to degenerated (deformed) spherulites is proposed. With a transcrystalline nylon 6 specimen the direction of the fastest growth in the unit cell (which forms the radius of spherulites) is found to be close to the a axis.     

A Revised Structure Model for the UCl6 Structure Type,Novel Modifications of UCl6 and UBr5, and a Comment on the Modifications of Protactinium Pentabromides

The redetermination of the crystal structure of trigonal UCl₆, which is the eponym for the UCl₆ structure type, showed that certain atomic coordinates had been incorrectly reported. This led to noticeably different U−Cl distances within the octahedral UCl₆ molecule (2.41 and 2.51 Å). Within the revised structure model presented here, which is based on single crystal data as well as quantum chemical calculations, all U−Cl distances are essentially equal within standard uncertainty (2.431(5), 2.437(5), and 2.439(6) Å). This room temperature modification, called rt-UCl₆, crystallizes in the trigonal space group P m1, No. 164, hP21, with a=10.907(2), c=5.9883(12) Å, V=616.9(2) ų, Z=3 at T=253 K. A new low-temperature (lt) modification of UCl₆ is also presented that was obtained by cooling a single crystal of rt-UCl_6. The phase change occurs between 150 and 175 K. lt-UCl₆ crystallizes isotypic to a low-temperature modification of SF₆ in the monoclinic crystal system, space group C2/m, No. 12, mS42, with a=17.847(4), b=10.8347(18), c=6.2670(17) Å, β=96.68(2)°, V=1203.6(5) ų, Z=6 at 100 K. The Cl anions form a close-packed structure corresponding to the α-Sm type with uranium atoms in the octahedral voids. During the synthesis of UBr₅ a new modification was obtained that crystallizes in the triclinic crystal system, space group P , No. 2, aP36, with a=10.4021(6), b=11.1620(6), c=12.2942(7) Å, α=68.3340(10)°, β=69.6410(10)° and γ=89.5290(10)°, V=1231.84(12) ų, Z=3 at T=100 K. In this structure the UBr₅ units are dimerized to U₂Br₁₀ molecules. The Br anions also form a close-packed structure of the α-Sm type with adjacent uranium atoms in the octahedral voids. Comparisons of the crystal structures of the compounds MX₅ (M=Pa, U; X=Cl, Br) show that the crystal structure of monoclinic α-PaBr₅ is probably not correct.     

Dynamics and biological relevance of epigenetic N6-methyladenine DNA modification in eukaryotic cells

DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes. With the recent development of highly selective and sensitive bioanalytical techniques,N⁶-methyladenine（6mA） has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans. Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development, stress respon...     

Oxidation and nitrosation of 4-(3-alkylureido)-2, 2, 6, 6-tetramethylpiperidine-1-oxyls to 4-(3-alkyl-3-nitrosoureido)-2, 2, 6, 6-tetramethyl-1-oxopiperidinium salts

4-(3-Alkylureido)-2, 2, 6, 6-tetramethylpiperidine-1-oxyls are rapidly oxidized by N₂O₄ or NOCl to 4-(3-alkylureido)-2, 2, 6, 6-tetramethyl-1-oxopiperidinium nitrates and chlorides, which are then nitrosated to 4-(3-alkyl-3-nitrosoureido)-2, 2, 6, 6-tetramethyl-1-oxopiperidinium salts. The perchlorates of the latter were prepared by an exchange reaction with HClO₄. The nitrosation of alkylureidooxoammonium salts is the first example of chemical modification of oxoammonium derivatives in which the highly reactive >N⁺=O group is inert toward the reagent.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 542–547, March, 1993.     

Bromine Pentafluoride BrF5, the Formation of [BrF6]− Salts,and the Stereochemical (In)activity of the Bromine Lone Pairs

BrF₅ can be prepared by treating BrF₃ with fluorine under UV light in the region of 300 to 400 nm at room temperature. It was analyzed by UV-Vis, NMR, IR and Raman spectroscopy. Its crystal structure was redetermined by X-ray diffraction, and its space group was corrected to Pnma. Quantum-chemical calculations were performed for the band assignment of the vibrational spectra. A monoclinic polymorph of BrF₅ was quantum chemically predicted and then observed as its low-temperature modification in space group P2₁/c by single crystal X-ray diffraction. BrF₅ reacts with the alkali metal fluorides AF (A=K, Rb) to form alkali metal hexafluoridobromates(V), A[BrF₆] the crystal structures of which have been determined. Both compounds crystallize in the K[AsF₆] structure type (R , no. 148, hR24). For the species [BrF₆]⁺, BrF₅, [BrF₆]⁻, and [IF₆]⁻, the chemical bonds and lone pairs on the heavy atoms were investigated by means of intrinsic bond orbital analysis.     

A new layered perovskite,KSrNb2O6F,by powder neutron diffraction

The structure of a new layered oxyfluoride, viz. potassium strontium diniobium hexaoxide fluoride, KSrNb₂O₆F, was refined from powder neutron diffraction data in the orthorhombic space group Immm. The oxyfluoride compound is an n = 2 member of the Dion–Jacobson‐type family of general formula A[A′_n−1B_nX_3n+1], which consists of double layered perovskite slabs, [SrNb₂O₆F]⁻, between which K⁺ ions are located. Within the perovskite slabs, the NbO₅F octahedra are significantly distorted and tilted about the a axis. A bond‐valence‐sum calculation gives evidence for O/F ordering in KSrNb₂O₆F, with the F⁻ ions located in the central sites of the corner‐sharing NbO₅F octahedra along the b axis. All atoms lie on special positions, namely Nb on m, Sr on mmm, K on m2m, F on mm2, and O on sites of symmetry m and m2m.