Bromo Substituents Research Articles

The 2-Amino Group of 8-Aza-7-deaza-7-bromopurine-2,6-diamine and Purine-2,6-diamine as Stabilizer for the Adenine-Thymine Base Pair in Heterochiral DNA with Strands in Anomeric Configuration.

Stabilization of DNA is beneficial for many applications in the fields of DNA therapeutics, diagnostics, and materials science. Now, this phenomenon is studied on heterochiral DNA, an autonomous DNA recognition system with complementary strands in α‐D and β‐D configuration showing parallel strand orientation. The 12‐mer heterochiral duplexes were constructed from anomeric (α/β‐D) oligonucleotide single‐strands. Purine‐2,6‐diamine and 8‐aza‐7‐deaza‐7‐bromopurine‐2,6‐diamine 2′‐deoxyribonucleosides having the capability to form tridentate base pairs with dT were used to strengthen the stability of the dA–dT base pair. T m data and thermodynamic values obtained from UV melting profiles indicated that the 8‐aza‐7‐deaza 2′‐deoxyribonucleoside decorated with a bromo substituent is so far the most efficient stabilizer for heterochiral DNA. Compared with that, the stabilizing effect of the purine‐2,6‐diamine 2′‐deoxyribonucleoside is low. Global changes of helix structures were identified by circular dichroism (CD) spectra during melting.

Completing the β,γ-CXY-dNTP Stereochemical Probe Toolkit: Synthetic Access to the dCTP Diastereomers and 31P and 19F NMR Correlations with Absolute Configurations.

Nucleoside 5'-triphosphate (dNTP) analogues in which the β,γ-oxygen is mimicked by a CXY group (β,γ-CXY-dNTPs) have provided information about DNA polymerase catalysis and fidelity. Definition of CXY stereochemistry is important to elucidate precise binding modes. We previously reported the (R)- and (S)-β,γ-CHX-dGTP diastereomers (X = F, Cl), prepared via P,C-dimorpholinamide CHCl (6a, 6b) and CHF (7a, 7b) bisphosphonates (BPs) equipped with an (R)-mandelic acid as a chiral auxiliary, with final deprotection using H2/Pd. This method also affords the β,γ-CHCl-dTTP (11a, 11b), β,γ-CHF (12a, 12b), and β,γ-CHCl (13a, 13b) dATP diastereomers as documented here, but the reductive deprotection step is not compatible with dCTP or the bromo substituent in β,γ-CHBr-dNTP analogues. To complete assembly of the toolkit, we describe an alternative synthetic strategy featuring ethylbenzylamine or phenylglycine-derived chiral BP synthons incorporating a photolabile protecting group. After acid-catalyzed removal of the (R)-(+)-α-ethylbenzylamine auxiliary, coupling with activated dCMP and photochemical deprotection, the individual diastereomers of β,γ-CHBr- (33a, 33b), β,γ-CHCl- (34a, 34b), β,γ-CHF-dCTP (35a, 35b) were obtained. The β,γ-CH(CH3)-dATPs (44a, 44b) were obtained using a methyl (R)-(-)-phenylglycinate auxiliary. 31P and 19F NMR Δδ values are correlated with CXY stereochemistry and pKa2-4 values for 13 CXY-bisphosphonic acids and imidodiphosphonic acid are tabulated.

Synthesis and Determination of Thermotropic Liquid Crystalline Behavior of Cinnamaldehyde-Based Molecules with Two Schiff Base Linking Units.

A series of liquid crystal molecules with two Schiff base linking units and a cinnamaldehyde core with different terminal groups were synthesized and characterized. The intermediates of 4-heptyloxybenzaldehyde (1a) and 4-dodeyloxybenzaldehyde (1b) were synthesized through the alkylation of 4-hydroxybenzaldehyde with a series of bromoalkane. A condensation reaction of cinnamaldehyde, 1,4-phenylenediamine and a series of substituted benzaldehydes with different terminal groups such as bromo, chloro, hydroxy, cinnamaldehyde, hydrogen, methoxy, heptyloxy and dodecyloxy produced a series of new cinnamaldehyde-based compounds, 2–9, respectively. All these compounds were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and CHN elemental analysis. The liquid crystal properties of these compounds were determined using polarized optical microscopy (POM), and their transitions were further confirmed using differential scanning calorimetry (DSC). Compounds with chloro, bromo, methoxy, heptyloxy, and dodecyloxy substituents are mesogenic compounds with nematic phase behavior. However, the other compounds were found to be non-mesogenic without any mesophase transitions. The structure–property relationship was investigated in order to study the effect of different terminal groups and Schiff base linking units on the liquid crystalline behavior of these compounds.

Model Substrate/Inactivation Reactions for MoaA and Ribonucleotide Reductases: Loss of Bromo, Chloro, or Tosylate Groups from C2 of 1,5-Dideoxyhomoribofuranoses upon Generation of an α-Oxy Radical at C3.

We report studies on radical-initiated fragmentations of model 1,5-dideoxyhomoribofuranose derivatives with bromo, chloro, and tosyloxy substituents on C2. The effects of stereochemical inversion at C2 were probed with the corresponding arabino epimers. In all cases, the elimination of bromide, chloride, and tosylate anions occurred when the 3-hydroxyl group was unprotected. The isolation of deuterium-labeled furanone products established heterolytic cleavage followed by the transfer of deuterium from labeled tributylstannane. In contrast, 3-O-methyl derivatives underwent the elimination of bromine or chlorine radicals to give the 2,3-alkene with no incorporation of label in the methyl vinyl ether. More drastic fragmentation occurred with both of the 3-O-methyl-2-tosyloxy epimers to give an aromatized furan derivative with no deuterium label. Contrasting results observed with the present anhydroalditol models relative to our prior studies with analogously substituted nucleoside models have demonstrated that insights from biomimetic chemical reactions can provide illumination of mechanistic pathways employed by ribonucleotide reductases (RNRs) and the MoaA enzyme involved in the biosynthesis of molybdopterin.

Acridine Variations for Coordination Chemistry

AbstractThis study describes the synthesis of an acridone through the directed lithiation of a diarylamine, and elaboration via the 4,5‐dibromoacridone. The bromo substituents are amenable to Suzuki‐Miyaura coupling. Conversion to a 9‐chloro‐4,5‐dibromoacridine, followed by bromine‐lithium exchange, allows the preparation of a 4,5‐bis (phosphino)‐9‐chloroacridine. The 9‐chloro moiety undergoes nucleophilic aromatic substitution by methoxide or an aryloxide. One‐electron reduction of a 9‐(aryloxy)‐4,5‐bis(phosphino)acridine affords a stable radical anion.

Structural properties and photocatalytic degradation efficiency of CuO and erbium doped CuO nanostructures prepared by thermal decomposition of some Cu-salophen type complexes as precursors

CuO and Er-doped CuO nanostructures were synthesized by thermal decomposition of Cu-salophen complexes containing chloro, bromo and nitro substituents as precursors (CuL1, CuL2 and CuL3, respectively). The structure of products was characterized by FT-IR spectroscopy and XRD patterns. XRD patterns indicated that the formation of single-phase monoclinic structures without impurity and also confirmed that erbium ions are successfully doped into CuO crystal lattice. The photocatalytic activity of all samples was measured against the Reactive Black 5 dye under UV radiation. The photocatalytic mineralization of RB-5 was monitored by total organic concentration (TOC) decrease and changes in the UV–Vis spectra. The results revealed that the photocatalytic efficiency of Er-doped CuO samples is much higher than their un-doped counterparts. The highest percentage of dye decomposition was achieved using Er-doped CuO (1). The optical band gaps calculated from UV–Vis spectra were found to be 3.60 eV for both CuO (1) and Er-doped CuO (1). The PL spectrum of Er-doped CuO (1) showed a significant decrease in emission intensity, which was related to the electron-hole separation due to electron transfer from CuO conductive band to Er3+ ions. The BET analysis revealed after Er3+ doping, the surface porosity and specific surface area increased because of the appearance of some surface defects in CuO structure. FE-SEM images of both pure and doped CuO samples displayed that the powders consist of highly agglomerated nano-flakes resulting from overlapping of small particles. Further analysis of Er-doped CuO (1) with TEM indicated the prepared sample is composed of nanoparticles.

Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioamination of unactivated alkenes have been developed, providing novel synthetic routes to access synthetically challenging quaternary carbon-centered ben...

Facile synthetic route to fluoroalkylated carboranes by copper-catalyzed reaction of fluoroalkane sulfonyl bromides with allyl carboranes

Fluoroalkanesulfonyl bromides, RFSO2Br, RF = CF3, CF2CO2Et, CF2CF2OCH3, were used for addition of fluoroalkyl groups to the double bonds of allylcarboranes. These synthetic transformations were smoothly proceeded in good yields using the copper-catalysis approach to afford a variety of bromofluoroalkyl-containing target molecules. Nucleophilic substitution of the bromo substituent in some prepared compounds was shown to lead to further diverse carborane functionalization.

Late-stage peptide C\u2013H alkylation for bioorthogonal C\u2013H activation featuring solid phase peptide synthesis

Methods for the late-stage diversification of structurally complex peptides hold enormous potential for advances in drug discovery, agrochemistry and pharmaceutical industries. While C–H arylations emerged for peptide modifications, they are largely limited to highly reactive, expensive and/or toxic reagents, such as silver(I) salts, in superstoichiometric quantities. In sharp contrast, we herein establish the ruthenium(II)-catalyzed C–H alkylation on structurally complex peptides. The additive-free ruthenium(II)carboxylate C–H activation manifold is characterized by ample substrate scope, racemization-free conditions and the chemo-selective tolerance of otherwise reactive functional groups, such as electrophilic ketone, bromo, ester, amide and nitro substituents. Mechanistic studies by experiment and computation feature an acid-enabled C–H ruthenation, along with a notable protodemetalation step. The transformative peptide C–H activation regime sets the stage for peptide ligation in solution and proves viable in a bioorthogonal fashion for C–H alkylations on user-friendly supports by means of solid phase peptide syntheses.

Synthesis of Phenanthro[9,10-c]thiophenes by 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-Promoted Cyclo-Oxidation.

A new method to prepare phenanthro[9,10-c]thiophenes has been developed. In the presence of triflic acid, 3,4-diaryl thiophenes undergo 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-promoted cyclo-oxidation. NMR and computational studies indicate that protonation of the thiophene plays a key role in this reaction. The reaction can be used to prepare phenanthro[9,10-c]thiophene, as well as derivatives with alkyl, bromo, and methoxy substituents. However, the yields and selectivity of the reaction depend on both the nature and location of the substituents. Bis(3-methoxyphenyl)thiophene reacts under these conditions to give the desired product in 57 % yield, while bis(4-methoxyphenyl)thiophene gives no product. Bis(3-bromophenyl)thiophene did not react, but cyclo-oxidation of bis(4-bromophenyl)thiophene provides the desired product in 34 % yield.

Efficient Syntheses of New Super Lewis Basic Tris(dialkylamino)-Substituted Terpyridines and Comparison of Their Methyl Cation Affinities.

Syntheses of very electron-rich dialkylamino-substituted 2,2':6',2''-terpyridines (TPYs) were adapted to moderate scale preparation without tedious purification of intermediates. The key 4'-bromo-6,6''-dimethyl-2,2':6',2''-terpyridine-4,4''-diyl bisnonaflate is now available in gram quantities. Its nucleophilic aromatic substitution with dimethylamine provided mixtures of 4'-bromo-substituted 4,4''-bis(dimethylamino)-TPY and the tris(dimethylamino)-TPY. The bromo compound was used in a Buchwald-Hartwig amination to provide the tris(dimethylamino)-TPY in excellent yield. The 4'-bromo substituent was reductively removed to furnish the bis(dimethylamino)-TPY. The same sequence of reactions with pyrrolidine as nucleophile leads to the hitherto unknown pyrrolidino-TPYs. Calculations at the MP2(FC)/6-31+G(2d,p)//B98/6-31G(d) level predict very high methyl cation affinities for compounds of this type, with the 4,4',4''-tri(pyrrolidin-1-yl)-TPY being the most Lewis basic TPY synthesized to date. The efficiently prepared electron-rich TPYs should be excellent ligands for many applications.

Synthesis and evaluation of new isatin-aminorhodanine hybrids as PIM1 and CLK1 kinase inhibitors

A series of new hybrid isatin-aminorhodanine molecules was prepared by microwave activation under mild conditions. Unexpected condensation of isatin derivatives at C-5 position of aminorhodanine was highlighted and confirmed by NMR and X-ray analyses. The inhibitory activity of these compounds was evaluated towards eight protein kinases, CDK's-2,-5,-9; PIM-1, CLK-1, Haspin, GSK3β and DYRK1A, whose signaling pathway dysregulation is associated to multifactorial diseases such as cancer, inflammatory, cardiovascular, and neurodegenerative diseases. Compound 3l bearing a bromo substituent has shown a potent and selective Pim1 kinase inhibitor activity.

Substituent effects on linear and nonlinear optical properties of fluorescent (E)-2-(4-halophenyl)-7-arlstyrylimidazo[1,2-A]pyridine: spectroscopic and computational methods

Abstract Effects of alkylamino and bromo substituents on imidazo[1,2-a]pyridines containing donor-π-acceptor type groups were comprehensively investigated for their linear and nonlinear optical properties by solvatochromic and DFT (CAM-B3LYP and BHandHLYP) methods. The difference between the ground and excited dipole moments as well as their ratios obtained by solvatochromic analysis indicate that the excited state is more polar than the ground state for both the bromo and diethyl amino derivative. More than twofold enhancement in the excited state dipole moments was observed as revealed by the difference and ratio of dipole moment upon the introduction of alkylamino donor group and these suggest large intramolecular charge transfer in the dyes. Stabilization energy above 20 kJ/mol was observed for large number of electron donor–acceptor interactions in Natural Bonding Orbital (NBO) analysis. Bond length alternation (BLA) and Bond order alternation (BOA) values tend to zero suggesting a high degree of polarization in the dyes. Enhancement in mean polarizability (α0), first hyperpolarizability (β0) and second static hyperpolarizabilities ( $\bar \gamma$) were observed by the introduction of alkylamino and bromo group in place of chloro in spite of the fact that Hammett constant of chloro and bromo are the same. The dyes have fundamental and intrinsic properties within the Hamiltonian limits. The two-photon absorption cross section value (≈100 GM) is comparable with LDS-698, a commercial TPA dye. This investigation is important for understanding the electronic structure of imidazo[1,2-a]pyridine with active functional groups and extending the potential for optical applications.

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives.

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2'- and C-4' of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.

Pentanuclear iron catalysts for water oxidation: substituents provide two routes to control onset potentials.

The development of robust and efficient molecular catalysts based on earth-abundant transition metals for water oxidation reactions is a challenging research target. Our group recently demonstrated the high activity and stability of a pentairon-based water oxidation electrocatalyst (M. Okamura,M. Kondo, R. Kuga, Y. Kurashige, T. Yanai, S. Hayami, V. K. K. Praneeth, M. Yoshida, K. Yoneda, S. Kawata and S. Masaoka, Nature, 2016, 530, 465-468). However, the development of strategies to decrease onset potentials for catalysis remains challenging. In this article, we report the construction of a series of pentanuclear iron complexes by introducing electron-donating (methyl) and electron-withdrawing (bromo) substituents on the ligand. Two newly synthesized complexes exhibited five reversible redox processes, similar to what is seen with the parent complex. These complexes can also serve as homogeneous catalysts for water oxidation reactions, and the faradaic efficiencies of the reactions were high. Additionally, the onset potentials of the newly developed complexes were lower than that of the parent complex. Mechanistic insights revealed that there are two methods for decreasing onset potentials: control of the redox potentials of the pentairon complex and control of the reaction mechanism.

Enantioselective Cobalt(III)-Catalyzed C-H Activation Enabled by Chiral Carboxylic Acid Cooperation.

The enantioselective cobalt(III)-catalyzed C-H alkylation was achieved through the design of a novel chiral acid. The cobalt(III)-catalyzed enantioselective C-H activation was characterized by high position-, regio- and enantio-control under exceedingly mild reaction conditions. Thereby, the robust cooperative cobalt(III) catalysis proved tolerant of valuable electrophilic functional groups, including hydroxyl, bromo, and iodo substituents. Mechanistic studies revealed a considerable additive effect on kinetics and on a negative non-linear-effect.

Enantioselective Cobalt(III)‐Catalyzed C−H Activation Enabled by Chiral Carboxylic Acid Cooperation

AbstractThe enantioselective cobalt(III)‐catalyzed C−H alkylation was achieved through the design of a novel chiral acid. The cobalt(III)‐catalyzed enantioselective C−H activation was characterized by high position‐, regio‐ and enantio‐control under exceedingly mild reaction conditions. Thereby, the robust cooperative cobalt(III) catalysis proved tolerant of valuable electrophilic functional groups, including hydroxyl, bromo, and iodo substituents. Mechanistic studies revealed a considerable additive effect on kinetics and on a negative non‐linear‐effect.

Functionalization of an alkyd resin with (meth)acrylate groups for photoinitiated polymerization

Alkyd resin based on phthalic acid, soybean oil, pentaerythritol, and a small amount on fumaric acid was synthesized and functionalized with (meth)acrylate groups. Functionalization was carried out in two different ways. These were direct acrylation of the alkyd resin using acrylic acid and N-bromo succinimide on the one hand and a two step synthesis starting with epoxidation of the internal double bonds comprising in the alkyd resin followed by ring opening reaction with (meth)acrylic acid in a consecutive reaction on the other hand. The (meth)acrylate functionalized alkyd resins were characterized by 1H- and 13C NMR spectroscopy, FT-IR spectroscopy, GPC, iodine value (IN), and glass transition temperature (Tg). Photoinitiated polymerization of the functionalized alkyd resins using bis(4-methoxybenzoyl) diethyl germanium as photoinitiator was investigated by photo-DSC under nitrogen and in the presence of air. The maximum of the polymerization rate (Rpmax), the time (tmax) to obtain Rpmax, and the conversion on double bonds give information about the strong increase in the reactivity of the (meth)acrylate functionalized alkyd resins caused by their (meth)acrylate substituents. Additional bromo or hydroxy substituent attribute to reactivity differences between the functionalized alkyd resins. Moreover, (meth)acrylate functionalized alkyd resins were investigated as additives (10 wt %) in traditional monomers (1,6-hexanediol diacrylate, 1,6-hexanediol dimethacrylate, trimethylolpropane triacrylate, and trimethylolpropane trimethacrylate) or in acrylate functionalized methyl oleate model monomers. Photo-DSC investigation of the mixtures under nitrogen and in the presence of air showed no significant influence of the hydroxy substituted (meth)acrylated alkyd resin additives on photopolymerization kinetics of the traditional monomers. Although incorporation of bromine into the acrylated alkyd resin resulted in a slight decrease of both the Rpmax value and the conversion on double bonds if used as additive in a mixture comprising trimethylolpropane triacrylate or 9-acryloyloxy-10-bromo methyl oleate. Hydroxy substituted (meth)acrylated alkyd resins may be prefered as additives in traditional monomers.

The Effect of Bromo Substituents on the Multifaceted Emissive and Crystal‐Packing Features of Cyclic Triimidazole Derivatives

AbstractThe understanding of the mechanisms involved in crystal packing effects on the photophysical properties of a molecular entity is fundamental to engineer solid materials for specific applications. In fact, besides rigidification and protection from oxygen quenching, crystal packing influences the emissive properties through specific interactions. In the present work, by a critical comparison among the mono‐ (1Br), di‐ (2Br) and tri‐bromo (3Br) derivatives of triimidazo[1,2‐a : 1′,2′‐c : 1′′,2′′‐e][1,3,5]triazine, the role of their structural features on the multifaceted emission, spanning from dual fluorescence to ultralong phosphorescence, is elucidated. In particular, conformational distortions are found to be responsible for dual fluorescence, halogen‐bonding interactions are at the origin of the long‐lived phosphorescence and π‐π interactions resulting in the formation of columnar or dimeric H‐aggregates induce room‐temperature ultralong phosphorescence.

Synthesis of 2‐Aryl‐ and 2‐Haloarylbenzimidazole‐N1‐acetamido Conjugates and a Preliminary Evaluation of Their Antifungal Properties

AbstractA series of new 2‐arylbenzimidazole‐N‐1 acetamido conjugates have been synthesized and characterized. Their antifungal activities were evaluated against fluconazole‐resistant C. albicans and A. fumigatus by the inhibition zone technique and were compared with the standard amphotericin B. Minimum inhibitory concentrations were determined for the most potent compounds, after preliminary structure‐activity analysis. Based upon these results a sub‐set of twelve ethylglycinyl ester conjugates bearing fluoro, chloro or bromo substituents on the 2‐phenyl moiety were examined for structure‐activity relationships using an agarose diffusion method employing a hypersensitive Sacharomyces cerevisiae strain. None of these compounds however showed significant activity at the concentrations tested. Single‐crystal X‐ray determinations were conducted on two of the newly synthesized compounds and were compared with DFT computational analysis.