Α-hydroxyl Group Research Articles

Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2Y14 Receptor Antagonists.

P2Y14 receptor (P2Y14R) is activated by extracellular UDP-glucose, a damage-associated molecular pattern that promotes inflammation in the kidney, lung, fat tissue, and elsewhere. Thus, selective P2Y14R antagonists are potentially useful for inflammatory and metabolic diseases. The piperidine ring size of potent, competitive P2Y14R antagonist (4-phenyl-2-naphthoic acid derivative) PPTN 1 was varied from 4- to 8-membered rings, with bridging/functional substitution. Conformationally and sterically modified isosteres included N-containing spirocyclic (6-9), fused (11-13), and bridged (14, 15) or large (16-20) ring systems, either saturated or containing alkene or hydroxy/methoxy groups. The alicyclic amines displayed structural preference. An α-hydroxyl group increased the affinity of 4-(4-((1R,5S,6r)-6-hydroxy-3-azabicyclo[3.1.1]heptan-6-yl)phenyl)-7-(4-(trifluoromethyl)phenyl)-2-naphthoic acid 15 (MRS4833) compared to 14 by 89-fold. 15 but not its double prodrug 50 reduced airway eosinophilia in a protease-mediated asthma model, and orally administered 15 and prodrugs reversed chronic neuropathic pain (mouse CCI model). Thus, we identified novel drug leads having in vivo efficacy.

Infrared Reflection-Absorption Spectroscopy of α-Hydroxyacids at the Water-Air Interface.

Organic molecules, including α-hydroxyacids, are ubiquitous in the natural environment. Often found at water-air interfaces, organic molecules can alter the structure of the interface or participate in interfacial chemistry. Despite their prevalence in the environment, the structure and ordering of α-hydroxyacids have not been widely investigated at water-air interfaces, and the impact of the hydrophobic tail length on structure has not been explored. Here, for the first time, we use infrared reflection-absorption spectroscopy to assess the vibrational structure of α-hydroxyacids at a water surface as a function of surface partitioning and surface coverage. We study lactic acid, 2-hydroxyoctanoic acid, and 2-hydroxystearic acid, which have 1 carbon, 6 carbon, and 16 carbon tails, respectively. Vibrational features compared across the set of α-hydroxyacids studied here are used to determine the interaction of the polar headgroup with the water subphase and the ordering of the hydrophobic tail. We find that the carbonyl and α-hydroxyl groups participate in a complex hydrogen-bonding motif at the water-air interface that can be affected by the hydrophobic tail length and places the polar headgroup in or below the water-air interface. Furthermore, molecular ordering increases with the tail length or the surface coverage. The presence of the α-hydroxyl group causes the α-hydroxyacids to maintain a tilted orientation with respect to the surface normal even at high surface coverages. A combination of polar headgroup and hydrophobic tail effects dictates the overall orientation of α-hydroxyacids and can thus affect their ability to participate in chemistry and alter organic coatings on water surfaces.

Enhancing β-aryl ether bond cleavage of lignin model dimer via benzylic alcohol dehydration

Lignin has immense potential for the production of monoaromatics that can be further prepared as target chemicals or alkyl biofuels. In this work, experiments and density functional theory (DFT) calculations were employed to investigate the effect of benzylic alcohol (α-hydroxyl group, CαH─OH) dehydration to α,β-alkenyl group (Cα = Cβ) on the enhancement of the β-aryl ether (β-O-4) bond cleavage reactivity of lignin model dimer over Pd/C by formic acid. This study demonstrated that the β-O-4 bond cleavage reactivity was significantly enhanced via the benzylic alcohol dehydration to Cα = Cβ. The cleavage reactivity of the β-O-4 bond attached to Cα functional groups was in the order of α-hydrogen atom (CαH─H) > CαH─OH > α-carbonyl group (Cα = O). An easy formation of the CαH─H from the Cα = Cβ hydrogenation led to the enhancement of the β-O-4 bond cleavage reactivity being achieved. The β-O-4 bond cleavage rate was increased by 6.2 times in the presence of the CαH─H compared to the Cα = O. Due to few and lower required energy barriers after CαH─OH dehydration, the β-O-4 bond attached to the Cα = Cβ was more thermodynamically favorable to be cleaved. The work highlights the prospect of efficient depolymerization of lignin into monoaromatics.

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of <i>Erythrina</i> Alkaloids

Electrochemical heterodifunctionalization of α-CF3alkenes to access α-trifluoromethyl-β-sulfonyl tertiary alcohols

An unprecedented electrochemical heterodifunctionalization of α-CF3alkenes with benzenesulfonyl hydrazides was accomplished in this work, wherein a β-sulfonyl and a α-hydroxyl group were simultaneously incorporated across the olefinic double bond in a single operation.

2-Hydroxy-Docosahexaenoic Acid Is Converted Into Heneicosapentaenoic Acid via α-Oxidation: Implications for Alzheimer’s Disease Therapy

Alzheimer’s disease (AD) is a neurodegenerative disease with as yet no efficient therapies, the pathophysiology of which is still largely unclear. Many drugs and therapies have been designed and developed in the past decade to stop or slow down this neurodegenerative process, although none has successfully terminated a phase-III clinical trial in humans. Most therapies have been inspired by the amyloid cascade hypothesis, which has more recently come under question due to the almost complete failure of clinical trials of anti-amyloid/tau therapies to date. To shift the perspective for the design of new AD therapies, membrane lipid therapy has been tested, which assumes that brain lipid alterations lie upstream in the pathophysiology of AD. A hydroxylated derivative of docosahexaenoic acid was used, 2-hydroxy-docosahexaenoic acid (DHA-H), which has been tested in a number of animal models and has shown efficacy against hallmarks of AD pathology. Here, for the first time, DHA-H is shown to undergo α-oxidation to generate the heneicosapentaenoic acid (HPA, C21:5, n-3) metabolite, an odd-chain omega-3 polyunsaturated fatty acid that accumulates in cell cultures, mouse blood plasma and brain tissue upon DHA-H treatment, reaching higher concentrations than those of DHA-H itself. Interestingly, DHA-H does not share metabolic routes with its natural analog DHA (C22:6, n-3) but rather, DHA-H and DHA accumulate distinctly, both having different effects on cell fatty acid composition. This is partly explained because DHA-H α-hydroxyl group provokes steric hindrance on fatty acid carbon 1, which in turn leads to diminished incorporation into cell lipids and accumulation as free fatty acid in cell membranes. Finally, DHA-H administration to mice elevated the brain HPA levels, which was directly and positively correlated with cognitive spatial scores in AD mice, apparently in the absence of DHA-H and without any significant change in brain DHA levels. Thus, the evidence presented in this work suggest that the metabolic conversion of DHA-H into HPA could represent a key event in the therapeutic effects of DHA-H against AD.

Structural, biological and pharmaceutical importance of antibiotic agent chloramphenicol.

The vibrational, magnetic resonance and electronic spectral techniques are used to evaluate structural activity associated physico-chemical properties. The biological affinity and drug importance was validated by calculating biological parameters using HyperChem. Mulliken charge assignment for restoring chemical potential for generating drug potential in the molecular site was mapped and analyzed. The vibrational spectral pattern was estimated by identifying active and inactive bands and hindrance of vibrational activity of Acetamide group was monitored and thereby drug malfunction was tested. The chemical reaction pathway around the core carbons of chain and ring was keenly noted and the cause of chemical potential for the inducement of drug mechanism was reported. The stimulation of chemical mechanism for antibiotic activity was addressed by suitable evidence and further improvement for enhancing activity was made. The electronic HOMO and LUMO interaction over different molecular entities are discussed to expose accompany of drug mechanical transitions. The CT complex was recognized to be C=N and C=C bonds and operating drug mechanism was monitored. The unwanted drug property induced by perplexes of charge depletion on α-hydroxyl group was assessed from MEP map. The hyperactive polarization energy of 266.18 X10−33 esu and 327 X10−33 esu of present compound is causing biological activity in good order. The uncontrolled breathing region of Acetamide group was clarified in VCD profile and this is main cause to produce toxicity in drug process.

The Generation of the Oxidant Agent of a Mononuclear Nonheme Fe(II) Biomimetic Complex by Oxidative Decarboxylation. A DFT Investigation.

The oxidative decarboxylation of the iron(II) α-hydroxy acid (mandelic acid) complex model, biomimetic of Rieske dioxygenase, has been investigated at the density functional level. The explored mechanism sheds light on the role of the α-hydroxyl group on the dioxygen activation. The potential energy surfaces have been explored in different electronic spin states. The rate-determining step of the process is the proton transfer. The oxidative decarboxylation preferentially takes place on the quintet state.

Studies of the Complexation of Gluconate with Th(IV) in Acidic Solutions: Stability Constant Determination and Coordination Mode Analysis.

Gluconate is a multidentate ligand and its complexation with actinides has received increasing attention because of its existence in high level nuclear wastes as well as in nuclear waste repositories. In this work, the complexation of gluconate with Th(IV) was studied in deuterated water (D2O) by pD titrations and nuclear magnetic resonance (NMR) spectroscopy. In the pCD range 2.0-4.6, gluconate (GD4-) forms two 1:1 complexes with Th(IV), Th(GD3)2+ and Th(GD2)+. Their stability constants were determined to be log β(D)101(-1) = 1.04 ± 0.12 for Th4+ + GD4- = Th(GD3)3+ + D+ and log β(D)101(-2) = -(1.31 ± 0.09) for Th4+ + GD4- = Th(GD2)+ + 2D+ at I = 1.0 mol·L-1 NaClO4 and t = 22 °C. The coordination modes of these two complexes were also analyzed. In both complexes, the tridentate chelation forms through the binding of Th(IV) to one oxygen from the carboxylate group and two oxygens from α- and γ-hydroxyl groups. The difference is that in Th(GD2)+, both α- and γ-hydroxyl groups deprotonate, and in Th(GD3)2+, only the α-hydroxyl group deprotonates.

Investigation of Mechanistic Pathway for Trimethyl Borate Mediated Amidation of (R)-Mandelic Acid for the Synthesis of Mirabegron, an Antimuscarinic Agent

The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active α-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing α-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.

Identification of Copper(II)–Lactate Complexes in Cu2O Electrodeposition Baths: Deprotonation of the α-Hydroxyl Group in Highly Concentrated Alkaline Solution

Unveiling dissolved species in electrodeposition baths helps our understanding of electrodeposition behavior, such as growth orientation. A highly concentrated aqueous alkaline copper(II)–lactate solution is used for the electrodeposition of copper(I) oxide (Cu2O) thin films with <111> orientations; the semiconductor properties of these films facilitate their use in solar-cell materials, photocathodes, and photocatalysts. However, the dissolved species, presumably copper(II)–lactate complexes, cannot be deduced on the basis of known thermodynamic data, and have not been convincingly determined yet. In this work, we determine these cupric complexes by pH titration, ultraviolet–visible spectroscopy, and electrospray-ionization mass spectrometry (ESI-MS), including probe-ESI-MS (PESI-MS). Using PESI-MS, we successfully analyzed a highly concentrated solution without sample dilution. The determined complexes are Cu(H–1L)L− and Cu(H–1L)22–, where the H–1L2− (CH3CH(O−)COO−) is a lactate ion with a deprotonated α-hydroxyl group. As far as we know, this is the first direct experimental observation of H–1L2− ions in a highly concentrated aqueous alkaline copper(II)–lactate solution. We also propose that H–1L2– is stabilized by the high concentration and through coordination to copper(II) ions.

Elaborated spectral, modeling, QSAR, docking, thermal, antimicrobial and anticancer activity studies for new nanosized metal ion complexes derived from sulfamerazine azodye

New azodye ligand (H2L) and its relative Cr(III)-, Mn(II)-, Fe(III)-, Co(II)-, Ni(II)-, Cu(II)-, Zn(II)- and Cd(II)-nanosized complexes were prepared. A new synthesized compounds were characterized using spectral (mass, IR, UV–Vis, XRD, and ESR) and analytical (elemental, molar conductance, thermal and magnetic moment measurements) tools. Infrared spectra showed that the ligand behaves as a monobasic bidentate, coordinating with central atoms through carbonyl oxygen and α-hydroxyl group. The geometrical structures of Cr(III) and Fe(III) complexes were found to be in octahedral configuration, whereas Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes have tetrahedral forms. XRD patterns reflect an amorphous appearance of all investigated complexes. TEM images showed nanosized particles and identical distribution over the complex surface. Molecular modeling for the drug ligand and its metal ion complexes were performed using Gaussian09 program to assert on their structural formulae. Some essential parameters were extracted using HOMO and LUMO energies. AutoDock tools 4.2 was used to simulate the interaction process with infected cell proteins to expect the experimental pathway. The inhibition activity of drug ligand and its metal ion complexes was evaluated towards different types of bacteria and fungi through in vitro antimicrobial activities. The antitumor activities of all compounds are straightened towards human liver carcinoma (HEPG2) cell lines. Fe(III) and Co(II) complexes exhibited IC50 of 2.90 and 4.23 µg mL−1, respectively, which means they are more potent anticancer drug than the standard (doxorubicin, IC50 = 4.73 µg mL−1). Therefore, the two complexes may consider promising anticancer drugs.

Ion mobility-mass spectrometry separation of steroid structural isomers and epimers

Drift tube ion mobility spectrometry (DTIMS) coupled with mass spectrometry was evaluated for its capabilities in rapid separation of endogenous isomeric steroids. These compounds, which included eight isomer groups, were investigated as protonated and sodiated species and collision cross sections were measured for all ionization species of each steroid. Pregnenolone (CCSN2 176.7 A2) and 5α-dihydroprogesterone (CCSN2 191.4 A2) could be separated as protonated species, and aldosterone (CCSN2 197.7 A2) and cortisone (CCSN2 211.7 A2) could be separated as sodiated monomers. However, the sodiated dimers of the remaining isomers yielded increased separation, resulting in baseline resolution. Specific structural differences including ring conformation and the chirality of hydroxyl groups were compared to evaluate their relative effects on collision cross section in isomers. These results indicated that C5 ring conformation isomers androsterone and etiocholanolone, which both contain a C3 α-hydroxyl group, yielded similar dimer CCS. Yet these compounds were well resolved from their respective β-hydroxyl epimers, trans-androsterone and epietiocholanolone. Alternative drift gases were evaluated, and carbon dioxide drift gas offered slight improvement in isomer resolution well, including allowing separation of testosterone (CCSCO2 330.0 A2), dehydroepiandrosterone (CCSCO2 312.6 A2), and epitestosterone (CCSCO2 305.6 A2). Finally, different metal cation adducts, including alkali, alkaline earth, and first row transition metal adducts were analyzed, and several of these species provided improved resolution between steroid epimers. Overall, this study shows that drift tube ion mobility is a promising tool for improved separation of isomeric steroids.

Copper(II) Complexes in Aqueous Alkaline Copper(II)-Lactate Solutions for Electrodeposition of Copper(I) Oxide

Copper(I) oxide (Cu2O), a ubiquitous oxide known as an intrinsic p-type semiconductor with 2.1 eV bandgap, has attracted increasing attention as the material for less-expensive n-ZnO / p-Cu2O solar cell. The electrodeposition of Cu2O from aqueous deposition baths was first reported by Rakhshani and co-workers [1], and further developed by Swizer et al [2], Izaki and Shinagawa [3]. Basic aqueous deposition baths of Cu2O contain 0.4 M (i.e., mol dm-3) copper (II) salts (e.g., CuSO4, Cu(CH3COO)2, Cu(ClO4)2 etc.) with 3.0 M lactate (i.e. L– = C3H5O3 – ) as complex former. The baths are usually used under alkaline conditions with pH range from 9.5 to 12.5. However, the copper complex(es) dissolved in the basic lactate baths mentioned above still remains undetermined. According to a pH speciation diagram of the Cu(II)-lactate system (Fig. 1) calculated using formation constants of CuL+, CuL2, and CuL3 – tabulated in ref. [4], the baths tend to form Cu(OH)2 precipitate at pH > 8, whereas the basic deposition baths retain clearness even at pH 12.5. Thus, unknown cupric lactate complex(es) would be formed in the alkaline region. To determine the unknown Cu(II)-lactate complex(es), possible candidates have been discussed firstly. The presence of CuL3 – is questionable since Jahn-Teller d 9 Cu2+ ion always forms a square-planar complex instead of an octahedral one, e.g., CuL3 –, which exceeds 18 electrons. Fig. 2 shows a couple of titration curves in which experiment 1 refers to a traditional titration curve acquired by titrating 50 mL of 0.4 M Cu(ClO4)2-3.0 M lactic acid (HL) aqueous solution with NaOH, while the plots for experiment 2 were obtained by measuring dozens of 15 mL of 0.4 M Cu(ClO4)2-3.0 M lactic acid baths neutralized with 24 different amount of the NaOH. Here, we measured the pH values several days after the NaOH addition. It turned out that the c NaOH of final equivalence point for experiment 1, e.g., (A), is smaller than that for experiment 2, e.g., (B). In other words, the final equivalent point (A) underestimates c NaOH required for the formation of unknown cupric lactate complex(es). The deviation of the point (A) from (B) may well be attributed to a relatively slow formation rate of the complex(es). Because of the slow rate, a part of the complex(es) formation remains unfinished within the time-scale of traditional titration. In contrast, the experiment 2 with enough reaction time reaches the exact final equivalence point (B), at which c NaOH = c HL + 2c Cu(II), indicating that the final Cu(II)-lactate complex is Cu(H–1L)2 2– (H–1L = C3H4O3 –, formed by the deprotonation of α-hydroxyl-group.). In order to observe the Cu(H–1L)2 2– complex directly, mass spectra for the solution were measured by electrospray ionization. For 0.4 M Cu(II)-3.0 M lactic acid solution with pH 9.5, a set of anions, [Cu(H–1L)L·(NaL) x ]– where x = 0–3, were observed at m/z = 240, 352, 464, 576 as doublets due to the isotopes of copper 63Cu/65Cu(100/45), using negative ion mode electrospray ionization [5]. In this case, however, the solution was diluted by pure water on the occasion of the measurement. In contrast, undiluted original solution of pH 7–11 also successfully gave a sequence of signals attributed to [Cu(H–1L)2·Na3](NaL) x + where x = 0, 1, 2, … at m/z = 308, 420, 532, … by employing novel probe electrospray ionization in positive ion mode [6]. These results clearly indicate the presence of Cu(H–1L)2 2– species. Since such deprotonation of α-hydroxyl group could never happen for free i.e. uncoordinated lactate ions, the formation of Cu(H–1L)2 2– at pH 7–11 is due to a strong Lewis acidity of Cu2+ ions, especially in a concentrated solution with relatively high ionic strength. We actually observed the formation of Cu(OH)2 precipitate as Fig. 1 indicates, if the solution (pH 9.5) is highly diluted.In order to discuss other possible cupric lactate complex(es) that may exist in the Cu(II)-lactate aqueous solution, a set of UV-vis absorption spectra for the samples of experiment 2 were measured (Fig. 3). Beyond pH 6, which is also beyond the neutralization point of HL, two different couples of isosbestic points were observed, implying that there are two different chemical equilibria in this region, in each of them two dominant Cu(II)-species are in equilibrium. Based on the discussion of possible candidates for unknown cupric lactate complex(es) as well as the results of titration and ESI-MS, the two kinds of chemical equilibria most likely to be equilibrium (A) CuL2 + OH­– = Cu(H–1L)L– and equilibrium (B) Cu(H–1L)L– + OH– = Cu(H–1L)2 2–. Hence, the most likely candidates instead of CuL3 – are Cu(H–1L)L– and Cu(H–1L)2 2–. Figure 1

New cytotoxic 19-norbufadienolide and bufogargarizin isolated from Chan Su

One new 19-norbufadienolide (1) and one new bufogargarizin (2), together with twelve known bufadienolides (3–14, resp.) were isolated from Chan Su, a traditional Chinese medicine that is used in the treatment of cancer. Their structures were elucidated on the basis of detailed spectroscopic analysis and comparison of corresponding data that is previously reported. The cytotoxic activities of the isolated compounds were evaluated on HeLa and A549 cell lines. Though 1 and 2 showed weak cytotoxic activities on both cell lines, compounds 4 and 5 showed lower IC50 values than bufalin, the most widely studied bufadienolide in Chan Su. Furthermore, four 3-ester derivatives (15–18) of compound 4 were synthesized and their cytotoxic activities were also evaluated. Analysis of the structure–activity relationship indicated that bufadienolides with aldehyde group at C-10 or α-hydroxyl group at C-11 exhibit stronger cytotoxic activities on both cell lines. The cytotoxic activity of arenobufagin-3-ester derivative 17 was 4-fold higher than compound 4.

Synthesis and biological evaluation of bile carboxamide derivatives with pro-apoptotic effect on human colon adenocarcinoma cell lines

We previously reported that the cinnamylpiperazinyl group in the side chain of the chenodeoxycholic acid showed apoptosis-inducing activity on multiple myeloma cancer cell line KMS-11. In the present study, we synthesized and tested the pro-apoptotic potency of fifteen new piperazinyl bile carboxamide derived from cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic and lithocholic acids on human colon adenocarcinoma cell lines DLD-1, HCT-116, and HT-29. Cell viability was first measured using XTT assay. The most of the synthetic bile carboxamide derivatives decreased significantly cell viability in a dose-dependent manner. HCT-116 and DLD-1 cell lines were more sensitive than HT-29 to tested compounds. 9c, 9d showed the best in vitro results in term of solubility and dose–response effect on the three colon adenocarcinoma cell lines. Additionally, flow cytometric and Western-blotting analysis showed that 9c induced pro-apoptosis in DLD-1 and HCT-116 whereas 9d did not. We conclude that the benzyl group improved anti-proliferative activity and that the α-hydroxyl group was found to be more beneficial at the 7-position in steroid skeleton.

Raman, surface-enhanced Raman, and density functional theory characterization of (diphenylphosphoryl)(pyridin-2-, -3-, and -4-yl)methanol.

This work presents near-infrared Raman spectroscopy (FT-RS) and surface-enhanced Raman scattering (SERS) studies of three pyridine-α-hydroxymethyl biphenyl phosphine oxide isomers: (diphenylphosphoryl)(pyridin-2-yl)methanol (α-Py), (diphenylphosphoryl)(pyridin-3-yl)methanol (β-Py), and (diphenylphosphoryl)(pyridin-4-yl)methanol (γ-Py) adsorbed onto colloidal and roughened in oxidation-reduction cycles silver surfaces. The molecular geometries in the equilibrium state and vibrational frequencies were calculated by density functional theory (DFT) at the B3LYP 6-311G(df,p) level of theory. The results imply that the most stable structure of the investigated molecules is a dimer created by two intermolecular hydrogen bonds between the H atom of the α-hydroxyl group (in up (HOU) or down (HOD) stereo bonds position) and the O atom of tertiary phosphine oxide (═O) of the two monomers. Comparison the FT-RS spectra with the respective SERS spectra allowed us to predict the orientation of the hydroxyphosphonate derivatives of pyridine that depends upon both the position of the substituent relative to the ring N atom (in α-, β-, and γ-position, respectively) and the type of silver substrate.

Probing of the pH-Dependent Redox Mechanism of a Biologically Active Compound, 5,8-Dihydroxynaphthalene-1,4-dione

The redox behaviour of a potential anticancer organic compound, 5,8-dihydroxynaphthalene-1,4-dione (DND), was investigated in 1 : 1 buffered aqueous ethanol using cyclic, differential pulse, and square wave voltammetry. The redox processes were found to occur in a pH-dependent diffusion-controlled manner. Presence of an α-hydroxyl group stabilised semiquinone radical of DND, formed by the gain of 1 e– and 1 H+, prevented the second step reduction, which is in contrast to the general mechanism previously reported for quinines in protic and aprotic media. In addition, our results supported an independent oxidation and reduction process. Square wave voltammetry provided evidence about the reversible and quasi-reversible nature of oxidation and reduction peaks. Based on the voltammetric results, the electrode reaction mechanism of DND was proposed. Parameters including pKa, transfer coefficient, diffusion coefficient, and electron transfer rate constant were evaluated. The values of pKa obtained from cyclic voltammetry and ultraviolet-visible spectroscopy not only agreed with each other, but also with reported values of structurally related compounds evaluated by other techniques.

Synthesis, spectral, antitumor and antimicrobial studies on Cu(II) complexes of purine and triazole Schiff base derivatives

A series of copper (II) complexes of Schiff bases derived from 7H-2,6-diaminopurine and 4H-3,5-diamino-1,2,4-triazole with 2-pyridinecarbaldehyde, salicylaldehyde, 2,4-dihydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde have been prepared. The donor atoms and the possible geometry of the complexes were investigated by means of elemental and thermal analyses, molar conductance, magnetic moment, UV–Vis, IR, ESR and mass spectra. The ligands behaved as tetradentate, coordinating through the nitrogen atom of the azomethine group and the nearest nitrogen atom to it or oxygen atom of α-hydroxyl group. The results of simultaneous DTA & TGA analyses of the complexes showed the final degradation product for these complexes is CuO. The spectral studies confirmed a four coordinate environment around the metal ion. The obtained results were supported by 3D molecular modeling of complexes using molecular mechanics (MM+) and semiempirical molecular orbital calculations (PM3). These complexes were also tested for their in vitro antimicrobial activities against some bacterial and fungal strains. Complex 2 was investigated for its cyctotoxic effect against human breast cancer (MCF7), liver carcinoma (HEPG2) and colon carcinoma cell lines (HCT116). This compound exhibited a moderate activity against the tested cell lines with IC50 of 10.3, 9.8 and 8.7μg/ml against MCF7, HCT116 and HEPG2, respectively.

Structures Required of Polyphenols for Inhibiting Advanced Glycation end Products Formation

The properties of polyphenols as AGEs formation inhibitors have attracted great interest among researchers. This review discusses the antiglycation activities of polyphenols and focuses on the relationship between the AGEs formation inhibitory activities and their chemical structures. The molecular structures influence the inhibition in the following ways: (1) The hydroxylation on both A ring and B ring improved the inhibitory activity on AGEs formation, while hydroxylation on C ring decreased the activity. (2) The methylation generally reduced the anti-AGEs activity of flavonoids, except for the 3-O-methylation of flavonols. (3) The glycosylation of hydroxyls of flavonoids tended to decrease the inhibitory activities on inhibiting AGEs formation, although contradictionary results were existed. (4) Hydrogenation of the C2=C3 double bond of flavones slightly weakened their activities. (5) A 5,7-dihydroxy structure was favorable to the activity of isoflavones. (6) Proanthocyanidins dimer or trimers showed a stronger inhibitory activity than catechins, and the glucosides of anthocyanidin had higher activities than their rutinosides. (7) The hydroxylation on B ring and the methylation of stilbenes decreased the inhibitory activity. (8) Presence of galloyl groups was important for the activity of catechins, and α-hydroxyl group at C-3 was much more effective than β-hydroxyl group at C-3. (9) The phenolic acids with multiple hydroxyls showed strong inhibition against AGEs formation, and an ortho or meta dihydroxyl structure on the benzene ring was vital to the anti-AGEs activity of anthraquinone. (10) Both ellagic acids and ellagitannins showed potent inhibitory activities on AGEs formation, and hydroxylation increased the activities but methylation decreased them.