Aromatic Ring Systems Research Articles

Photo protection of RNA building blocks: Adenosine 5′-monophosphate, cytidine 5′-monophosphate and cytosine

Photoprotection of the RNA nucleotides adenosine 5′-monophosphate and cytidine 5′-monophosphate, and the nucleobase cytosine was studied using UV pump, IR probe femtosecond transient absorption spectroscopy. The excitation energy is contained in the aromatic ring system, protecting the RNA backbone. All three molecules dissipate the excitation energy by internal conversion and subsequent vibrational relaxation to the electronic ground state in less than 10ps. In addition, a second deactivation channel is found in cytidine 5′-monophosphate, illustrated by a signal at 1563cm−1 with a lifetime of 33ps assigned to an nπ∗ state in agreement with observations in the UV region.

ChemInform Abstract: Silver‐Catalyzed Regioselective Synthesis of Acridines, Quinolines, and Naphthalenes from 3‐(2‐Alkynyl)aryl‐β‐ketoesters.

AbstractThis is a mild and efficient method for the synthesis of a variety of fused aromatic ring systems.

Novel molecular-level evidence of iodine binding to natural organic matter from Fourier transform ion cyclotron resonance mass spectrometry

Major fractions of radioiodine (129I) are associated with natural organic matter (NOM) in the groundwater and surface soils of the Savannah River Site (SRS). Electrospray ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was applied to elucidate the interactions between inorganic iodine species (iodide and iodate) and a fulvic acid (FA) extracted from a SRS surface soil. Iodate is likely reduced to reactive iodine species by the lignin- and tannin-like compounds or the carboxylic-rich alicyclic molecules (CRAM), during which condensed aromatics and lignin-like compounds were generated. Iodide is catalytically oxidized into reactive iodine species by peroxides, while FA is oxidized by peroxides into more aliphatic and less aromatic compounds. Only 9% of the total identified organo-iodine compounds derived from molecules originally present in the FA, whereas most were iodine binding to newly-produced compounds. The resulting iodinated molecules were distributed in three regions in the van Krevelen diagrams, denoting unsaturated hydrocarbons, lignin and protein. Moreover, characteristics of these organo-iodine compounds, such as their relatively low O/C ratios (<0.2 or <0.4) and yet some degree of un-saturation close to that of lignin, have multiple important environmental implications concerning possibly less sterically-hindered aromatic ring system for iodine to get access to and a lower hydrophilicity of the molecules thus to retard their migration in the natural aquatic systems. Lastly, ~69% of the identified organo-iodine species contains nitrogen, which is presumably present as NH2 or HNCOR groups and a ring-activating functionality to favor the electrophilic substitution. The ESI-FTICR-MS technique provides novel evidence to better understand the reactivity and scavenging properties of NOM towards radioiodine and possible influence of NOM on 129I migration.

Novel insights into the fungal oxidation of monoaromatic and biarylic environmental pollutants by characterization of two new ring cleavage enzymes

The phenol-degrading yeast Trichosporon mucoides can oxidize and detoxify biarylic environmental pollutants such as dibenzofuran, diphenyl ether and biphenyl by ring cleavage. The degradation pathways are well investigated, but the enzymes involved are not. The high similarity of hydroxylated biphenyl derivatives and phenol raised the question if the enzymes of the phenol degradation are involved in ring cleavage or whether specific enzymes are necessary. Purification of enzymes from T. mucoides with catechol cleavage activity demonstrated the existence of three different enzymes: a classical catechol-1,2-dioxygenase (CDO), not able to cleave the aromatic ring system of 3,4-dihydroxybiphenyl, and two novel enzymes with a high affinity towards 3,4-dihydroxybiphenyl. The comparison of the biochemical characteristics and mass spectrometric sequence data of these three enzymes demonstrated that they have different substrate specificities. CDO catalyzes the ortho-cleavage of dihydroxylated monoaromatic compounds, while the two novel enzymes carry out a similar reaction on biphenyl derivatives. The ring fission of 3,4-dihydroxybiphenyl by the purified enzymes results in the formation of (5-oxo-3-phenyl-2,5-dihydrofuran-2-yl)acetic acid. These results suggest that the ring cleavage enzymes catalyzing phenol degradation are not involved in the ring cleavage of biarylic compounds by this yeast, although some intermediates of the phenol metabolism may function as inducers.

Binding of Serotonin to Lipid Membranes

Serotonin (5-hydroxytryptamine, 5-HT) is a prevalent neurotransmitter throughout the animal kingdom. It exerts its effect through the specific binding to the serotonin receptor, but recent research has suggested that neural transmission may also be affected by its nonspecific interactions with the lipid matrix of the synaptic membrane. However, membrane-5-HT interactions remain controversial and superficially investigated. Fundamental knowledge of this interaction appears vital in discussions of putative roles of 5-HT, and we have addressed this by thermodynamic measurements and molecular dynamics (MD) simulations. 5-HT was found to interact strongly with lipid bilayers (partitioning coefficient ~1200 in mole fraction units), and this is highly unusual for a hydrophilic solute like 5-HT which has a bulk, oil-water partitioning coefficient well below unity. It follows that membrane affinity must rely on specific interactions, and the MD simulations identified the salt-bridge between the primary amine of 5-HT and the lipid phosphate group as the most important interaction. This interaction anchored cationic 5-HT in the membrane interface with the aromatic ring system pointing inward and a prevailing residence between the phosphate and the carbonyl groups of the lipid. The unprotonated form of 5-HT shows the opposite orientation, with the primary amine pointing toward the membrane core. Partitioning of 5-HT was found to decrease lipid chain order. These distinctive interactions of 5-HT and model membranes could be related to nonspecific effects of this neurotransmitter.

Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

Heterocycles as Nonclassical Bioisosteres of α‐Amino Acids

Bioisosterism of α-amino acids is often accomplished by replacing the α-carboxylate with one of the many known carboxylic acid bioisosteres. However, bioisosterism of the whole α-amino acid moiety is accomplished with heterocyclic bioisosteres that often display an acidic function. In this Minireview, we summarized the reported heterocycles as nonclassical bioisosteres of α-amino acids, which include quinoxaline-2,4(1H)-dione, quinoxaline-2,3(1H)-dione and quinolin-2(1H)-one, azagrevellin and azepine-derived structures. The binding mode of the crystalized bioisosteres were compared with those of the crystalized α-amino acids that bind in the same domain, and where no data on the crystal structure were available, the displacement studies of known orthosteric ligands were used. The reported bioisosteres share the following essential structural features for mimicking α-amino acids: an aromatic ring system joined to a lactam ring system with an acidic feature next to the lactam carbonyl, where this acidic feature together with the lactam carbonyl can mimic the α-carboxylate, and the lactam nitrogen together with the aromatic ring system can mimic the α-ammonium. The majority of these heterocycles can be prepared from three common corresponding starting materials: the corresponding anilines, isatins or anthranilic esters. The data collected here show the potential of this class of bioisosteres in the design of glutamate receptor ligands and beyond.

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide–2-nitrobenzoic acid (1/1)

In the asymmetric unit of the title co-crystal, C12H14N4O2S·C7H5NO4, the sulfamethazine and 2-nitro­benzoic acid mol­ecules form a heterodimer through inter­molecular amide–carb­oxy­lic acid N—H⋯O and carb­oxy­lic acid–pyrimidine O—H⋯N hydrogen-bond pairs, giving a cyclic motif [graph set R 2 2(8)]. The dihedral angle between the two aromatic ring systems in the sulfamethazine mol­ecule is 88.96 (18)° and the nitro group of the acid is 50% rotationally disordered. Secondary aniline N—H⋯Osulfone hydrogen-bonding associations give a two-dimensional structure lying parallel to the ab plane.

Synthesis and Antimycobacterial Activity of Symmetric Thiocarbohydrazone Derivatives against Mycobacterium bovis BCG.

In this work, we reported the synthesis and evaluation of antimycobacterial and antifungal activity of a series of thiocarbohydrazone derivatives which are thiacetazone congeners. The target compounds were synthesized in superior yields by reacting thiocarbohydrazide with different aromatic aldehydes and methyl ketones. Compounds 8, 19 and 25 were found to be the most potent derivatives, exhibiting acceptable activity against Mycobacterium bovis BCG compared to thiacetazone and ethambutol as reference substances. Compounds 8, 15 and 25 exhibited the highest activity against Candida albicans. The most active compounds had a completely different aromatic ring system with various electronic, steric and lipophilic natures. This is understandable in light of the fact that carbohydrazone derivatives must undergo a metabolic activation step before exerting their anti-TB activity and different SAR rules govern each one of these two processes.

Surface modification of anatase nanoparticles with fused ring salicylate-type ligands (3-hydroxy-2-naphthoic acids): a combined DFT and experimental study of optical properties

The surface modification of nanocrystalline TiO2 particles (45 Å) with salicylate-type ligands consisting of an extended aromatic ring system, specifically 3-hydroxy-2-naphthoic acid, 3,5-dihydroxy-2-naphthoic acid and 3,7-dihydroxy-2-naphthoic acid, was found to alter the optical properties of nanoparticles in a similar way to salicylic acid. The formation of the inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and a reduction in the band gap upon the increase in the electron delocalization when including an additional ring. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of a salicylate-type (binuclear bidentate binding-bridging) thus restoring the six-coordinated octahedral geometry of surface Ti atoms. From both absorption measurements in methanol/water = 90/10 solutions and steady-state quenching measurements of modifier fluorescence upon binding to TiO2 in aqueous solutions, stability constants in the order of 10(3) M(-1) have been determined at pH 2 and pH 3. Fluorescence lifetime measurements, in the presence and absence of colloidal TiO2 nanoparticles, indicated that the fluorescence quenching process is primarily static quenching, thus proving the formation of a nonfluorescent CT complex. The binding structures were investigated by using FTIR spectroscopy. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain the vibrational frequencies of charge transfer complexes, and the calculated values were then compared with the experimental data.

A pH sensitive ratiometric fluorophore and its application for monitoring the intracellular and extracellular pHs simultaneously.

Intracellular and extracellular pH plays a key role in many cell biological processes. Probes for simultaneously monitoring the pH change inside and outside living cells are rarely available. In this paper, we describe a new ratiometric pH fluorophore that was synthesized by condensation of 4-bromine-1,8-naphthalimides and 3-amino-1,2,4-triazole. In the range of pH 5-8, the only N-H in the heterocycle-fused aromatic ring system of this fluorophore undergoes a reversible deprotonation-protonation process, which results in a large red shift of the absorption and emission spectra. In aqueous solution, this fluorophore exhibits good pH selectivity, high photostability, high tolerance to ionic strength, and high fluorescence quantum yield in both the acid and base forms. A long chain derivative of this fluorophore (HNNA) was designed for cellular pH sensing. HNNA was found to locate on the membrane structure of the cells, and was successfully used for mapping the pH change in both the extracellular microenvironment and the inner cells by confocal imaging.

Polyphenols from the mangosteen (Garcinia mangostana) fruit for breast and prostate cancer

The mangosteen (Garcinia mangostana) is a tropical fruit native to Southeast Asia and has long been reported to contain multiple health promoting properties. This fruit is an abundant source of xanthones, a class of polyphenolic compounds with a distinctive tricyclic aromatic ring system and is largely responsible for its biological activities including anti-cancer activity. Herein we describe the anti-cancer activity and mechanisms of mangosteen polyphenolic xanthones including α-Mangostin against breast cancer and prostate cancer. So far, extracts and individual xanthones have been found to induce apoptosis and inhibit proliferation on cancer cells in vitro and in vivo. Based on the reported findings there is clear evidence that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate and breast cancer chemoprevention.

Species-specific lipophilicity of thyroid hormones and their precursors in view of their membrane transport properties

A total of 30 species-specific partition coefficients of three thyroid hormones (thyroxine, liothyronine, reverse liothyronine) and their two biological precursors (monoiodotyrosine, diiodotyrosine) are presented. The molecules were studied using combined methods of microspeciation and lipophilicity. Microspeciation was carried out by 1H NMR-pH and UV-pH titration techniques on the title compounds and their auxiliary derivatives of reduced complexity. Partition of some of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. Our data show that the iodinated aromatic ring system is the definitive structural element that fundamentally determines the lipophilicity of thyroid hormones, whereas the protonation state of the aliphatic part plays a role of secondary importance. On the other hand, the lipophilicity of the precursors is highly influenced by the protonation state due to the relative lack of overwhelmingly lipophilic moieties. The different logp values of the positional isomers liothyronine and reverse liothyronine represent the importance of steric and electronic factors in lipophilicity. Our investigations provided clear indication that overall partition, the best membrane transport – predicting physico-chemical parameter depends collectively on the site-specific basicity and species-specific partition coefficient. At physiological pH these biomolecules are strongly amphipathic due to the lipophilic aromatic rings and hydrophilic amino acid side chains which can well be the reason why thyroid hormones cannot cross membranes by passive diffusion and they are constituents of biological membranes.The lipophilicity profile of thyroid hormones and their precursors are calculated and depicted in terms of species-specific lipophilicities over the entire pH range.

Formation of coke during the pyrolysis of bio-oil

Bio-oil from the pyrolysis of biomass can be upgraded into high quality liquid biofuels or utilised as a feedstock to boilers and gasifiers. The coke formation is a particularly serious problem for the upgrading of bio-oil as well as the direct utilisation of bio-oil. The effects of bio-oil chemical composition on the coke formation are keys to the understanding of the mechanism of coke formation. A bio-oil sample produced from the fast pyrolysis of mallee wood at 500°C and the lignin-derived oligomers separated from the bio-oil were pyrolysed in a two-stage fluidised-bed/fixed-bed reactor at temperatures between 250 and 800°C. In addition to the quantification of coke yield, UV-fluorescence spectroscopy was used to trace the formation and evolution of aromatic ring systems during pyrolysis. Our results indicate that both water-soluble and water-insoluble bio-oil fractions can form coke even at very low temperatures. The interactions among the species derived from cellulose/hemicellulose and lignin, especially the interactions involving their oligomers, are important to the observed coke yield, especially at low temperatures.

Catalytic reforming of tar during gasification. Part IV. Changes in the structure of char in the char-supported iron catalyst during reforming

Our previous parts of this series have shown the char-supported iron catalysts to possess high activity for the reforming of tar during biomass gasification. This study aims to investigate the changes to the structure of char in the char-supported iron catalyst during the reforming of tar derived from the pyrolysis of mallee wood biomass. The char structure was characterised with Raman spectroscopy and its intrinsic reactivity at 400°C in a thermogravimetric analyser. The results showed that the Raman peak area in the range of 800–1800cm−1 of the catalysts changed slightly after being used for the steam reforming of biomass tar. The changes in the Raman band area ratio of ID/I(Gr+Vl+Vr) indicated that the relative ratio of larger and smaller aromatic ring systems increased after reforming at temperatures at 800°C or higher. The changes in the char-air reactivity before and after reforming provided further insights to the changes in char structure as well as the importance of alkali and alkaline earth metallic species deposited on the char-supported catalysts during reforming.

ChemInform Abstract: The Chemistry of Four‐Membered Aromatics

AbstractReview: 56 refs.

(1E,2E)-1,2-Bis[(1-benzyloxymethyl-1H-indol-3-yl)methylidene]hydrazine

The title compound, C34H30N4O2, lies on an inversion center and consists of two 3-substituted-1H-indole units linked by a 1,2-dimethyl­enehydrazine bridge. It is one of numerous examples in which two aromatic ring systems are joined by this 4-atom bridge. The geometry of the centrosymmetric bridge is: C(arom)—C = 1.444 (3), C=N = 1.284 (3), N—N = 1.414 (4) Å, C(arom)—C=N = 122.6 (2) and C=N—N = 111.9 (2)°. The nine non-H atoms of the indole unit lie in a plane (δr.m.s. = 0.0089 Å) which is twisted 6.0 (2)° with respect to the hydrazine bridge plane. The benzyl­oxymethyl substituents do not lie in the plane of the rest of the mol­ecule and are in a folded rather than an extended conformation. This is described by the three torsion angles in the middle of the C=N—C—O—CBz group, viz. 98.5 (3), −62.1 (3), and −66.3 (2)°.

ChemInform Abstract: A Facile Synthesis of 5,6‐Dihydro‐4H‐pyrrolo[3,4‐d]thiazole and Other Pyrrolidine‐Fused Aromatic Ring Systems via One‐Step Cyclization from Diols.

AbstractThe desired 5,6‐dihydro‐4H‐pyrrolo[3,4‐d]thiazole (VII) is readily prepared via a Mitsunobu reaction of diol (IV) with sulfonamide (V).

Molecular structure and O[sbnd]H⋯O hydrogen bond in 1-aryl-1,3-diketone malonates

The molecular structure of four 1,3-diketone malonates 1–4 were studied by analysis of geometric parameters obtained from single crystal X-ray diffraction experiments at 293K, displaying three sections: aromatic ring (4-substituted phenyl or naphthyl rings), H1O1C1C2C3O3 enol–keto (EK) system and a linear chain with dimethyl malonate. In the malonate moiety which is involved in C6, enolizable fragments are not observed. The two firsts moieties (aromatic ring and enolone system) are almost in a planar conformation. These results are well-supported by DFT B3LYP/6-31++G(d,p) calculations and MO analysis. These compounds are in the enol–keto (EK) tautomer. In comparison with a full π delocalized enolone (λQ=0.5), diketones 1–4 have a EK π-delocalization in the OH⋯O moiety because of the λQ values are between 0.283 and 0.321Å and showing values of O⋯O length between 2.488 and 2.567Å, which describe a resonance assisted hydrogen bonding (RAHB) and may be influenced by the additive effect of the CH2CH2CH(COOCH3)2 chain.

1,5,7,8′,11-Pentamethoxy-13H-spiro[dibenzo[a,g]fluorene-13,1′(4′H)-naphthalen]-4′-one toluene monosolvate

In the title compound, C35H28O6·C7H8, the dihedral angle between the mean planes through the naphthalene ring systems of the dibenzo[a,g]fluorene moiety is 22.44 (3)°. The aromatic ring system of the naphthalenone unit is approximately perpendicular to the mean plane of the five-membered ring, forming a dihedral angle of 87.51 (5)°. An intra­molecular C—H⋯O hydrogen bond is observed. In the crystal, pairs of C—H⋯π inter­actions link the mol­ecules, forming inversion dimers.