Accurate grading of brain gliomas by soft independent modeling of class analogy based on non‐negative matrix factorization of proton magnetic resonance spectra

Hydrogen magnetic resonance spectroscopy (¹H‐MRS) is a non‐invasive technique which provides a ‘frequency‐signal intensity’ spectrum of biochemical compounds of tissues in the body. Although this method is currently used in human brain studies, accurate classification of in‐vivo ¹H‐MRS is a challenging task in the diagnosis of brain tumors. Problems such as overlapping metabolite peaks, incomplete information on background component and low signal‐to‐noise ratio disturb classification results of this spectroscopic method. This study presents an alternative approach to the soft independent modeling of class analogy (SIMCA) technique, using non‐negative matrix factorization (NMF) for dimensionality reduction. In the adopted strategy, the performance of SIMCA was improved by application of a robust algorithm for classification in the presence of noisy measurements. Total of 219 spectra from two databases were taken by water‐suppressed short echo‐time ¹H‐MRS, acquired from different subjects with different stages of glial brain tumors (Grade II (26 cases), grade III (24 cases), grade IV (41 cases), as well as 25 healthy cases). The SIMCA was performed using two approaches: (i) principal component analysis (PCA) and (ii) non‐negative matrix factorization (NMF), as a modified approach. Square prediction error was considered to assess the class membership of the external validation set. Finally, several figures of merit such as the correct classification rate (CCR), sensitivity and specificity were calculated. Results of SIMCA based on NMF showed significant improvement in percentage of correctly classified samples, 91.4% versus 83.5% for PCA‐based model in an independent test set. Copyright © 2015 John Wiley & Sons, Ltd.     

Use of in vivo magnetic resonance spectroscopy for studying metabolic diseases

Owing to the worldwide obesity epidemic and the sedentary lifestyle in industrialized countries, the number of people with metabolic diseases is explosively increasing. Magnetic resonance spectroscopy (MRS), which is fundamentally similar to magnetic resonance imaging, can detect metabolic changes in vivo noninvasively. With its noninvasive nature, ¹H, ¹³C and ³¹P MRS are being actively utilized in clinical and biomedical metabolic studies to detect lipids and important metabolites without ionizing radiation. ¹H MRS can quantify lipid content in liver and muscle and can detect other metabolites, such as 2-hydroxyglutarate, in vivo. Of interest, many studies have indicated that hepatic and intramyocellular lipid content is inversely correlated with insulin sensitivity in humans. Thus, lipid content can be utilized as an in vivo biomarker for detecting early insulin resistance. Employing ¹³C MRS, hepatic glycogen synthesis and breakdown can be directly detected, whereas ³¹P MRS provides in vivo adenosine triphosphate (ATP) synthesis rates by saturation transfer methods in addition to ATP content. These in vivo data can be very difficult to assess by other methods and offer a critical piece of metabolic information. To aid the reader in understanding these new methods, fundamentals of MRS are described in this review in addition to promising future applications of MRS and its limitations.     

1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, 2‐ethyl‐5‐methylhexanamide and 2‐ethylpentanamide: three products of barbiturate decomposition

The three title compounds were obtained by reactions which mimic, with more extreme conditions, the in vivo metabolism of barbiturates. 1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, C₁₁H₁₈N₂O₂, (I), and 2‐ethylpentanamide, C₈H₁₇NO, (III), both crystallize with two unique molecules in the asymmetric unit; in the case of (III), one unique molecule exhibits whole‐molecule disorder. 2‐Ethyl‐5‐methylhexanamide, C₉H₁₉NO, (II), crystallizes as a fully ordered molecule with Z′ = 1. In the crystal structures, three different hydrogen‐bonding motifs are observed: in (I) a combination of R₂²(4) and R₂²(8) motifs, and in (II) and (III) a combination of R₄²(8) and R₂²(8) motifs. In all three structures, one‐dimensional ribbons are formed by N—H...O hydrogen‐bonding interactions.     

C?H···N and C?H···O intramolecular hydrogen bonding effects in the 1H, 13C and 15 N NMR spectra of the configurational isomers of 1‐vinylpyrrole‐2‐carbaldehyde oxime substantiated by DFT calculations

According to the ¹H, ¹³C and ¹⁵N NMR spectroscopic data and DFT calculations, the E‐isomer of 1‐vinylpyrrole‐2‐carbaldehyde adopts preferable conformation with the anti‐orientation of the vinyl group relative to the carbaldehyde oxime group and with the syn‐arrangement of the carbaldehyde oxime group with reference to the pyrrole ring. This conformation is stabilized by the C? H···N intramolecular hydrogen bond between the α‐hydrogen of the vinyl group and the oxime group nitrogen, which causes a pronounced high‐frequency shift of the α‐hydrogen signal in ¹H NMR (～0.5 ppm) and an increase in the corresponding one‐bond ¹³C–¹H coupling constant (ca 4 Hz). In the Z‐isomer, the carbaldehyde oxime group turns to the anti‐position with respect to the pyrrole ring. The C? H···O intramolecular hydrogen bond between the H‐3 hydrogen of the pyrrole ring and the oxime group oxygen is realized in this case. Due to such hydrogen bonding, the H‐3 hydrogen resonance is shifted to a higher frequency by about 1 ppm and the one‐bond ¹³C–¹H coupling constant for this proton increases by ～5 Hz. Copyright © 2008 John Wiley & Sons, Ltd.     

H(C)Ag: a triple resonance NMR experiment for 109Ag detection in labile silver‐carbene complexes

In silver complexes, indirect detection of ¹⁰⁹Ag resonances via ¹H,¹⁰⁹Ag‐HMQC frequently suffers from small or absent J_HAg couplings or rapid ligand dissociation. In these cases, it would be favourable to employ H(X)Ag triple resonance spectroscopy that uses the large one‐bond J_XAg coupling (where the donor atom of the ligand X is the relay nucleus). We have applied an HMQC‐based version of the H(C)Ag experiment to a labile silver‐NHC complex (NHC = N‐heterocyclic carbene) at natural ¹³C isotopic abundance and variable temperature. In agreement with simulations, H(C)Ag detection became superior to ¹H,¹⁰⁹Ag‐HMQC detection above ?20 °C. Copyright © 2014 John Wiley & Sons, Ltd.     

Supramolecular Interactions Direct the Formation of Two Structural Polymorphs from One Building Unit in a One‐Pot Synthesis

Two polymorphs of supramolecular isomers, a discrete dimer and a zig‐zag chain, having the same chemical composition, [Mn(Hbit)Cl₂] (Hbit=1‐methyl‐2‐(1H‐1,2,3‐triazol‐4‐yl)‐1H‐benzo[d]imidazole), were obtained solvothermally in a one‐pot synthesis. The isomers differ in a number of ways: orange blocks versus pale‐yellow needles, triclinic P versus orthorhombic Pbcn, double μ₂‐Cl versus alternate single and triple μ₂‐Cl, coordination number 5 versus 6, and antiparallel versus parallel near‐neighbor orientation of Hbit. The packing in each case is driven by the supramolecular interactions, H‐bonds (N?H???Cl, C?H???Cl) and π???π overlaps, calculated to be in the range 20–36 kcal mol^?1. Calculations gave a difference of only 2 kcal mol^?1 in favor of the dimer, which confirms with the observation of principally the dimer at short reaction time. ESI‐MS spectra of the dissolved crystals reveal the same fragments with similar distributions. The presence of two fragments at m/z 286.96 [Mn^IV(Hbit)Cl‐2H]⁺ and 323.94 [Mn^III(Hbit)Cl₂]⁺ indicates that [Mn(Hbit)Cl₂] is the building unit in both cases; thus, the different orientations of the ligands lead to the two polymorphs stabilized by the respective supramolecular interactions. Importantly, the chain form represents the first example with alternate single and triple μ₂‐Cl bridges. The magnetic interactions are weakly antiferromagnetic in both cases, with J in the range 0.07–0.34 cm^?1; however, high‐field EPR analysis reveals moderate magneto‐anisotropy with D=0.26(1) cm^?1, E=0.06(1) cm^?1 and D=0.17(1) cm^?1, E=0.03(1) cm^?1, respectively.     

A Convenient Synthesis and Biological Activity of Novel Pyrido[4,3‐d]pyrimidin‐4(3H)‐ones

Fifteen novel 2‐alkylamino‐3‐aryl‐8‐cyano‐5‐methyl‐7‐(methylthio)‐pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n , 6o were designed and have been successfully synthesized via tandem aza‐Wittig and annulation reactions with the corresponding iminophosphoranes 4 , aryl isocyanate, and amines in good yields. Their structures were clearly verified by IR spectroscopy, ¹H‐NMR spectroscopy, EI‐MS, and elemental analysis, and in the case of compound 6i , further analyzed by single‐crystal X‐ray diffraction. The preliminary results of an in vivo bioassay showed that some compounds display moderate antifungal activity.     

Design,Synthesis and Biological Evaluation of Isothiazole Based 1,2,4‐Trizaole Derivatives

A series of novel 3,4‐dichloroisothiazole based 1,2,4‐triazole derivatives were rationally designed and synthesized. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS or elemental analysis; the typical crystal structure was determined by X‐ray diffraction for validation. All target compounds were evaluated for their in vitro fungicidal and in vivo anti‐TMV activities. The bioassay results indicated that compound 6b , namely 1‐(3,4‐dichloroisothiazol‐5‐yl)‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanol, exhibited excellent growth inhibition against B. cinerea, C. arachidicola and P. piricola with median effective concentrations (EC₅₀) of 6.98, 2.73 and 3.07 μg/mL, respectively, and good in vivo anti‐TMV activity of over 60% of inactivation and induction activity at 100 μg/mL. These data demonstrate that compound 6b is both a fungicide and an anti‐TMV lead, deserving further studies.     

A Convenient Synthesis and Biological Activity of Novel Pyrido[4,3‐d]pyrimidin‐4(3H)‐ones

Fifteen novel 2‐alkylamino‐3‐aryl‐8‐cyano‐5‐methyl‐7‐(methylthio)‐pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n , 6o were designed and have been successfully synthesized via tandem aza‐Wittig and annulation reactions with the corresponding iminophosphorances 4 , aryl isocyanate, and amines in good yields. Their structures were clearly verified by IR, ¹H NMR, EI‐MS spectroscopy and elemental analysis, and in the case of compound 6i , analyzed by single‐crystal X‐ray diffraction further. The preliminary results of an in vivo bioassay showed that some compounds display moderate antifungal activity.     

Novel copper(II) heterochelate: synthesis,structural features and fluorescence studies

Fluorescence properties of four based derivatives [Aⁿ] (where n = 1–4) and their Cu(II) heterochelates of the type [Cu(Aⁿ)(CQ)(OH)]^?xH₂O {where A¹ = 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐4H‐furo[3,2‐c]chromen‐4‐one, A² = 8‐methyl‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐4H‐furo[3,2‐c]chromen‐4‐one, A³ = 6‐methyl‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐4H‐furo[3,2‐c]chromen‐4‐one, A⁴ = 8‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)‐4H‐furo[3,2‐c]chromen‐4‐one and x = 3, 2, 4, 1} were studied at room temperature. The fluorescence spectra of heterochelates show red shift, which may be due to the chelation by the ligands to the metal ion. It enhances ligand ability to accept electrons and decreases the electron transition energy. The kinetic parameters such as order of reaction (n), energy of activation (E_a), entropy (ΔS^#), pre‐exponential factor (A), enthalpy (ΔH^#) and Gibbs free energy (ΔG^#) have been reported. The antimicrobial activity of Clioquinol and Cu(II) heterochelates have been determined and described. All the heterochelates showed a more effective antimicrobial activity than the free ligand. Copyright © 2010 John Wiley & Sons, Ltd.     

GIAO,DFT, AIM and NBO analysis of the N?H···O intramolecular hydrogen‐bond influence on the 1J(N,H) coupling constant in push–pull diaminoenones

In the series of diaminoenones, large high‐frequency shifts of the ¹H NMR of the N? H group in the cis‐position relative to the carbonyl group suggests strong N? H···O intramolecular hydrogen bonding comprising a six‐membered chelate ring. The N? H···O hydrogen bond causes an increase of the ¹J(N,H) coupling constant by 2–4 Hz and high‐frequency shift of the ¹⁵N signal by 9–10 ppm despite of the lengthening of the relevant N? H bond. These experimental trends are substantiated by gauge‐independent atomic orbital and density functional theory calculations of the shielding and coupling constants in the 3,3‐bis(isopropylamino)‐1‐(aryl)prop‐2‐en‐1‐one (12) for conformations with the Z‐ and E‐orientations of the carbonyl group relative to the N? H group. The effects of the N? H···O hydrogen‐bond on the NMR parameters are analyzed with the atoms‐in‐molecules (AIM) and natural bond orbital (NBO) methods. The AIM method indicates a weakening of the N? H···O hydrogen bond as compared with that of 1,1‐di(pyrrol‐2‐yl)‐2‐formylethene (13) where N? H···O hydrogen bridge establishes a seven‐membered chelate ring, and the corresponding ¹J(N,H) coupling constant decreases. The NBO method reveals that the LP(O) →σ*_{N? H} hyperconjugative interaction is weakened on going from the six‐membered chelate ring to the seven‐membered one due to a more bent hydrogen bond in the former case. A dominating effect of the N? H bond rehybridization, owing to an electrostatic term in the hydrogen bonding, seems to provide an increase of the ¹J(N,H) value as a consequence of the N? H···O hydrogen bonding in the studied diaminoenones. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of the Magnetic Field on the Supramolecular Structure of Chiral Smectic C Phases: 2H NMR Studies

We present a theoretical and experimental ²H NMR study of the effect of external magnetic fields on the supramolecular organization of chiral smectic liquid‐crystalline mesophases, such as SmC* and re‐entrant SmC*. Three experimental cases in which the supramolecular helical structure of the smectic C* phase is unwound by a magnetic field (H), parallel to the helical axes of this phase, are discussed in detail. Unwinding of the helical structure is described by using a theoretical model based on the Landau‐de Gennes theory, which allows us to explain the transition temperatures among the SmA, SmC*, and uSmC* phases. The energy‐density behavior in the vicinity of the transitions and the value of the critical magnetic field H_C for unwinding the helical structure are discussed by applying this model to three ferroelectric smectogens ( MBHB , 11EB1M7 , ZLL7/* ), which are studied by ²H NMR spectroscopy at different magnetic fields (from 2.4 to 9.4 Tesla). Furthermore, the tilt angle of the three smectogens in the SmC* phase has been directly evaluated, for the first time, by comparing the quadrupolar splittings at different magnetic fields. In one case, ²H NMR angular measurements are used to obtain the tilt angle in the re‐entrant smectic C phase.     

Synthesis and cytotoxicity of silylalkylthio‐substituted N‐heterocycles and their hydroselenites

New hydroselenites of the different silylalkylthio‐substituted N‐heterocycles have been prepared by the reaction of selenium dioxide with N‐heterocycles in an aqueous medium. Their structure was confirmed by ¹H, ¹³C, and ⁷⁷Se NMR data. Most of these silylalkylthio‐substituted N‐heterocycles and their hydroselenites have an expressed cytotoxic activity on the MG‐22A (mouse hepatoma), HT‐1080 (human fibrosarcoma), B16 (mouse melanoma), and Neuro 2A (mouse neuroblastoma) cell lines. Some of the hydroselenites exhibit free‐radical protection simultaneously with a high cytotoxic effect. The substances studied were also active in vivoagainst sarcoma S‐180. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of New 1,2,3‐Triazole Derivatives Possessing 4H‐Pyran‐4‐one Moiety by 1,3‐Dipolar Cycloaddition Reaction of Azidomethyl Phenylpyrone with Various Alkynes

A series of new 1,2,3‐triazole derivatives were synthesized by 1,3‐dipolar cycloaddition reaction of 2‐(4‐azidomethylphenyl)‐6‐phenyl‐4H‐pyran‐4‐one with different alkynes in 40–71% yields. In the case of terminal alkynes, the reaction was proceeded in the presence of Cu(I) catalyst. The structure of the synthesized compounds were confirmed by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopy and elemental analysis.     

Studies on the Stereoselective Synthesis of Deuterated D‐Ribose Derivatives

In view of the importance of the site‐specific substitution of the H‐atom by its stable isotope ²H in a stereoselective/stereospecific manner at the pentose sugar residue, decreasing the spectral overcrowding in various regions of 1D and 2D homo‐ and heteronuclear correlation spectra of oligo‐DNA and ‐RNA, there is always a need for the development of new methods for the incorporation of ²H at different sites of a ribose. High‐yielding multistep syntheses of C(2)‐, and (5R)‐ and (5S)‐3,5‐deuterated ribose derivatives have been envisaged for the application of site‐specific incorporation of multilabeled nucleosides into oligomers to facilitate their structure elucidation by NMR spectroscopy. All syntheses started from D ‐glucose after proper derivatization. In the case of C(2), >97 atom‐% isotope was incorporated, employing an inversion of the configuration at C(2) as the key reaction. For C(5), two different routes were envisaged: on the one hand, deuterated achiral reagent was treated with a conformationally locked sugar moiety 15 , while, on the other, chiral protonated sources were used to transfer the H‐atom to a C(5)‐deuterated aldehyde 18 . In all cases, enantiomeric and isotopic purities were found to be as high as >97% as determined by NMR spectroscopy.     

Transition metal complexes of 1,2‐dihydroquinazolinone derivative,an emerging class of analgesic and anti‐inflammatory agents

A new 1,2‐dihydroquinazolinone, 2‐(2‐hydroxy‐phenyl)‐3‐[1‐(2‐oxo‐2H‐chromen‐3‐yl)‐ethylideneamino]‐2,3‐dihydro‐1H‐quinazolin‐4‐one (L) and its Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes have been prepared. These were characterized by elemental, spectral [UV–visible, IR, NMR (¹H, ¹³C and 2D heteronuclear correlation) and mass], conductance, magnetic susceptibility and thermal studies. The physicochemical data indicate that the ligand behaves as tridentate with ONO donor sequence towards the metal ions, and trigonal bipyramidal geometry was assigned for complexes. The ligand and its metal complexes were evaluated for their in vivo anti‐inflammatory and analgesic activity. The tested compounds have shown excellent activity, which are almost equipotent to the standard used in the study. Copyright © 2011 John Wiley & Sons, Ltd.     

Solution Behaviour and Biomolecular Interactions of Two Cytotoxic trans‐Platinum(II) Complexes Bearing Aliphatic Amine Ligands

A novel trans‐platinum(II) complex bearing one dimethylamine (dma) and one methylamine (ma) ligand, namely trans‐[PtCl₂(dma)(ma)], recently synthesised and characterised in our laboratory, displayed relevant antiproliferative properties in vitro, being more active than the parent complex, trans‐[PtCl₂(dma)(ipa)], which has isopropylamine (ipa) in place of methylamine. We have analysed comparatively the solution behaviour of these two complexes under various experimental conditions, and investigated their reactivity with horse heart cytochrome c by mass spectrometry, inductively coupled plasma–optical emission spectroscopy (ICP‐OES), 2D [¹H,¹⁵N],[¹H,¹³C] HSQC and [¹H,¹H] NOESY NMR. Some important changes that occurred in the [¹H,¹³C] HSQC NMR spectrum of cytochrome c treated with trans‐[PtCl₂(dma)(ma)] in water, after two days’ incubation, most probably arose from direct platinum coordination to the protein side chain; this was proved conclusively by [¹H,¹H] NOESY NMR and [¹H,¹⁵N] HSQC NMR measurements. Met65 was identified as the primary Pt binding site on cytochrome c. Electrospray mass spectrometry (ESIMS) results provided evidence for extensive platinum–protein adduct formation. A fragment of the [Pt(amine)(amine′)] type was established to be primarily responsible for protein metalation. ICP‐OES analysis revealed that these trans‐platinum(II) complexes bind preferentially to the serum proteins albumin and transferrin rather than to calf thymus DNA. Pt binding to DNA was found to be far lower than in the case of cisplatin. The implications of the results for the mechanism of action of novel cytotoxic trans‐platinum complexes are discussed.     

A simplified mass isotopomer approach to estimate gluconeogenesis rate in vivo using deuterium oxide

We compare a new simplified ²H enrichment mass isotopomer analysis (MIA) against the laborious hexamethylentetramine (HMT) method to quantify the contribution of gluconeogenesis (GNG) to total glucose production (GP) in calves. Both methods are based on the ²H labeling of glucose after in vivo administration of deuterium oxide. The ²H enrichments of plasma glucose at different C‐H positions were measured as aldonitrile pentaacetate (AAc) and methyloxime‐trimethylsilyl (MoxTMS) derivatives or HMT by gas chromatography/mass spectrometry (GC/MS). Two pre‐ruminating fasted Holstein calves (51 kg body mass, BM, age 7 days) received two oral bolus doses of ²H₂O (10 g/kg BM, 70 atom% ²H) at 7:00 h and 11:00 h after overnight food withdrawal. Blood samples for fractional GNG determination were collected at ?24 and between 6 and 9 h after the first ²H₂O dose. The ratio of ²H enrichments C5/C2 represents the contribution of GNG to GP. The ²H enrichment at C2 was calculated based on the ion fragments at m/z 328 (C1‐C6) ‐ m/z 187 (C3‐C6) of glucose AAc. The ²H enrichment at C5 was approximated either by averaging the ²H enrichment at C5‐C6 using the ion fragment of glucose MoxTMS at m/z 205 or by conversion of the C5 of glucose into HMT. The fractional GNG calculated by the C5‐C6 average ²H enrichment method (41.4 ± 6.9%) compared to the HMT method (34.3 ± 11.4%) was not different (mean ± SD, n = 6 replicates). In conclusion, GNG can be estimated with less laborious sample preparation by means of our new C5‐C6 average ²H enrichment method using AAc and MoxTMS glucose derivatives. Copyright © 2010 John Wiley & Sons, Ltd.     

Spectroscopic and X‐ray structural characterization of new polymeric organotin(IV) carboxylates and their in vitro antifungal activities: Part II

The reactions of R₃SnCl (R = Me, Bu or Ph) with sodium 4‐phenylbutyrate, Na(OPh^b), in EtOH yielded three polymeric triorganotin carboxylates, namely [R₃Sn(OPh^b)]_n (R = Me ( 1 ), Bu ( 2 ) or Ph ( 3 )). All complexes were spectroscopically characterized using Fourier transform infrared, ¹¹⁹Sn Mössbauer, ¹H NMR, ¹³C{¹H} NMR and ¹¹⁹Sn{¹H} NMR spectral techniques. In addition, the crystal structures of 1 and 3 were determined using single‐crystal X‐ray diffraction. Their polymeric structures are sustained by bridging carboxylates which connect two five‐coordinate Sn(IV) centres. Each metallic cation displays a distorted trigonal bipyramidal coordination geometry (Addison's parameters ranging from 0.84 in 1 to 0.77–0.91 in 3 ), with the oxygen atoms occupying the apical positions and the organic groups at the equatorial corners. The one‐dimensional zigzag chains of 1 propagate along the b ‐axis, whereas 3 displays wave‐like double polymeric chains along the b ‐axis. For both 1 and 3 , parallel one‐dimensional polymeric chains are interconnected by C─H⋅⋅⋅π interactions. The antifungal activity of 1 – 3 was screened against Candida albicans (ATCC 18804), C. tropicalis (ATCC 750), C. glabrata (ATCC 90030), C. parapsilosis (ATCC 22019), C. lusitaniae (CBS 6936) and C. dubliniensis (clinical isolate 28). The antifungal activity of 3 was noteworthy since it was not only more active than 1 and 2 , but also more active than the control drugs (nystatin and fluconazole nitrate) in some cases.     

Mechanistic Studies on the Oxidation of Glyoxylic and Pyruvic Acid by a [Mn4O6]4+ Core in Aqueous Media: Kinetics of Oxo‐Bridge Protonation

In aqueous media (pH 2.5–6.0), the Mn^IV tetramer [Mn₄(μ‐O)₆(bipy)₆]⁴⁺ ( 1 ⁴⁺; bipy = 2,2′‐bipyridine) oxidizes both glyoxylic and pyruvic acid to formic and acetic acid, respectively, under formation of CO₂. Kinetics studies suggest that the species 1 ⁴⁺, its oxo‐bridge protonated form [ 1 H]⁵⁺, i.e., [Mn₄(μ‐O)₅(μ‐OH)(bipy)₆]⁵⁺, the reducing acids (RH) and their conjugate bases (R^?) all take part in the reaction. The oxo‐bridge protonated oxidant [ 1 H]⁵⁺ was found to react much faster than 1 ⁴⁺. Thereby, the gem‐diol forms of the α‐oxo acids (especially in the case of glyoxylic acid) are the possible reductants. A one‐electron/one‐proton electroprotic mechanism operates in the rate‐determining step.