Models for the active site in galactose oxidase: structure, spectra and redox of copper(II) complexes of certain phenolate ligands

Galactose oxidase (GOase) is a fungal enzyme which is unusual among metalloenzymes in appearing to catalyse the two electron oxidation of primary alcohols to aldehydes and H2O2. The crystal structure of the enzyme reveals that the coordination geometry of mononuclear copper(II) ion is square pyramidal, with two histidine imidazoles, a tyrosinate, and either H2O (pH 7.0) or acetate (from buffer,pH 4-5) in the equatorial sites and a tyrosinate ligand weakly bound in the axial position. This paper summarizes the results of our studies on the structure, spectral and redox properties of certain novel models for the active site of the inactive form of GOase. The monophenolato Cu(II) complexes of the type [Cu(L1)X][H(L1) = 2-(bis(pyrid-2-ylmethyl)aminomethyl)-4-nitrophenol and X- = Cl- 1, NCS- 2, CH3COO- 3, ClO4 - 4] reveal a distorted square pyramidal geometry around Cu(II) with an unusual axial coordination of phenolate moiety. The coordination geometry of 3 is reminiscent of the active site of GOase with an axial phenolate and equatorial CH3COO- ligands. All the present complexes exhibit several electronic and EPR spectral features which are also similar to the enzyme. Further, to establish the structural and spectroscopic consequences of the coordination of two tyrosinates in GOase enzyme, we studied the monomeric copper(II) complexes containing two phenolates and imidazole/pyridine donors as closer structural models for GOase. N,N-dimethylethylenediamine and N,N'-dimethylethylenediamine have been used as starting materials to obtain a variety of 2,4-disubstituted phenolate ligands. The X-ray crystal structures of the complexes [Cu(L5)(py)], (8) [H2(L5) = N,N-dimethyl-N',N'-bis(2-hydroxy-4-nitrobenzyl) ethylenediamine, py = pyridine] and [Cu(L8)(H2O)] (11), [H2(L8) = N,N'-dimethyl-N,N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine] reveal distorted square pyramidal geometries around Cu(II) with the axial tertiary amine nitrogen and water coordination respectively. Interestingly, for the latter complex there are two different molecules present in the same unit cell containing the methyl groups of the ethylenediamine fragmentcis to each other in one molecule andtrans to each other in the other. The ligand field and EPR spectra of the model complexes reveal square-based geometries even in solution. The electrochemical and chemical means of generating novel radical species of the model complexes, analogous to the active form of the enzyme is presently under investigation

All-Pass Filter Based Linear Voltage Controlled Quadrature Oscillator

A linear voltage controlled quadrature oscillator implemented from a first-order electronically tunable all-pass filter (ETAF) is presented. The active element is commercially available current feedback amplifier (AD844) in conjunction with the relatively new Multiplication Mode Current Conveyor (MMCC) device. Electronic tunability is obtained by the control node voltage (V) of the MMCC. Effects of the device nonidealities, namely, the parasitic capacitors and the roll-off poles of the port-transfer ratios of the device, are shown to be negligible, even though the usable high-frequency ranges are constrained by these imperfections. Subsequently the filter is looped with an electronically tunable integrator (ETI) to implement the quadrature oscillator (QO). Experimental responses on the voltage tunable phase of the filter and the linear-tuning law of the quadrature oscillator up to 9.9 MHz at low THD are verified by simulation and hardware tests

Design of a Low-Power High-Gain Bio-Medical Operational Amplifier in 65nm Technology using gm/ID Methodology

Operational Amplifiers (Op-Amps) play a crucial role in the field of biomedical engineering, as they enable signal amplification and processing in various medical devices. With the increasing demand for portable and low-power biomedical devices, designing Op-Amps specifically tailored for such applications is essential. In response to this need, a low-power high-gain Op-Amp designed for biomedical applications using TSMC 65nm technology has been proposed. This Op-Amp incorporates a two-stage miller compensated topology, which is well-known for its superior performance in gain, gain bandwidth product and power consumption. The proposed Op-Amp contributes to the field of biomedical engineering by offering a tailored solution that enhances signal processing capabilities, enables accurate data acquisition, and improves overall efficiency in healthcare systems. The design methodology and simulation results presented in this paper provide insights into the performance and potential impact of the Op-Amp in advancing biomedical devices and systems

Exploring Music Genre Classification: Algorithm Analysis and Deployment Architecture

Music genre classification has become increasingly critical with the advent of various streaming applications. Nowadays, we find it impossible to imagine using the artist's name and song title to search for music in a sophisticated music app. It is always difficult to classify music correctly because the information linked to music, such as region, artist, album, or non-album, is so variable. This paper presents a study on music genre classification using a combination of Digital Signal Processing (DSP) and Deep Learning (DL) techniques. A novel algorithm is proposed that utilizes both DSP and DL methods to extract relevant features from audio signals and classify them into various genres. The algorithm was tested on the GTZAN dataset and achieved high accuracy. An end-to-end deployment architecture is also proposed for integration into music-related applications. The performance of the algorithm is analyzed and future directions for improvement are discussed. The proposed DSP and DL-based music genre classification algorithm and deployment architecture demonstrate a promising approach for music genre classification

Iron(III) complexes of certain tetradentate phenolate ligands as functional models for catechol dioxygenases

Catechol 1,2-dioxygenase (CTD) and protocatechuate 3,4-dioxygenase (PCD) are bacterial non-heme iron enzymes, which catalyse the oxidative cleavage of catechols tocis, cis-muconic acids with the incorporation of molecular oxygen via a mechanism involving a high-spin ferric centre. The iron(III) complexes of tripodal phenolate ligands containing N3O and N2O2 donor sets represent the metal binding region of the iron proteins. In our laboratory iron(III) complexes of mono- and bisphenolate ligands have been studied successfully as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The single crystal X-ray crystal structures of four of the complexes have been determined. One of thebis-phenolato complexes contains a FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. The Fe-O-C bond angle of 136.1° observed for one of the iron(III) complex of a monophenolate ligand is very similar to that in the enzymes. The importance of the nearby sterically demanding coordinated -NMe2 group has been established and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133, 148°). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulate the electronic spectral features, FeIII/FeII redox potentials and catechol cleavage activity of the complexes. Upon interacting with catecholate anions, two catecholate to iron(III) charge transfer bands appear and the low energy band is similar to that of catechol dioxygenase-substrate complex. Four of the complexes catalyze the oxidative cleavage of H2DBC by molecular oxygen to yield intradiol cleavage products. Remarkably, the more basic N-methylimidazole ring in one of the complexes facilitates the rate-determining productreleasing phase of the catalytic reaction. The present study provides support to the novel substrate activation mechanism proposed for the intradiol-cleavage enzymes

Synthesis, structure, spectra and redox of Cu(II) complexes of chelating bis(benzimidazole)-thioether ligands as models for electron transfer blue copper proteins

The tridentate ligand 1,5-bis(benzimidazol-2-yl)-3-thiapentane (L1) with N2S donor set forms the complex [Cu(L1)(H2O)Cl]Cl 1a and the linear quadridentate ligand 1,8-bis(benzimidazol-2-yl)-3,6-dithiaoctane (L2) with N2S2 donor set forms the complexes [Cu(L2)](ClO4)2·2H2O 2a and [Cu(L2)(NO3)]NO32b. The linear pentadentate ligand 1,11-bis(pyrid-2-yl)-3,6,9-trithiaundecane (L3) with N2S3 donor set forms the complex [Cu(L3)](ClO4)23. The perchlorate complex [Cu(L4)](ClO4)2·2CH3CN 4 of the pentadentate ligand, N,N-bis(benzimidazol-2-ylmethylthioethyl)methylamine (L4) with N3S2 donor set has also been isolated. In 1a Cu(II) is coordinated to the two benzimidazole nitrogens and thioether sulfur of the ligand L1, a chloride ion and a water molecule. The coordination geometry around copper is intermediate between trigonal bipyramidal and square pyramidal geometries and is better described as trigonal bipyramidal distorted square based pyramidal (TBDSBP) with the sulfur and nitrogen atoms and the chloride ion in the equatorial positions and the oxygen of water in the apical position. The coordination geometry around copper(II) in 2b is best described as trigonal bipyramidal, with both the thioether sulfur atoms [Cu-S(1), 2.529(5) and Cu-S(2), 2.438(6) Å] and one of the oxygen atoms of the nitrate ion [Cu-O(1), 2.066(13) Å] constituting the trigonal plane and both the benzimidazole nitrogens [Cu-N, 1.985(14) and 1.953(13) Å] occupying the axial positions. The bulky benzimidazole moieties of the ligand prevent the other nitrate ion from coordinating and favours trigonal bipyramidal geometry in spite of the presence of two six-membered chelate rings. In 4 the coordination plane of Cu(II) is comprised of two benzimidazole nitrogens, one thioether sulfur and N-methyl substituted amine nitrogen atom with the other thioether sulfur atom coordinated axially. The coordination geometry is best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The ligand field and EPR spectra of 1a, 2a and 2b are consistent with trigonal bipyramidal geometry in the solid state, whereas two ligand field bands in solution and an axial EPR spectrum in frozen solution were observed suggesting a change in coordination geometry to a square-based one on dissolution. The complexes 3 and 4 exhibit only one ligand field band in the solid state and axial EPR spectrum consistent with a square based geometry. All the complexes exhibit an intense S(σ ) → Cu(II) CT band in the range 330-380 nm and a high positive CuII/CuI redox potential

Axial versus equatorial coordination of thioether sulfur: mixed ligand copper(ii) complexes of 2-pyridyl-n-(2'-methylthiophenyl)-methyleneimine with bidentate diimine ligands

The synthesis, structure and spectral and redox properties of the copper(II) complexes [Cu(pmtpm)Cl2] (1) and [Cu(pmtpm)2](ClO4)2 (6), where pmtpm is the linear tridentate ligand 2-pyridyl-N-(2'-methylthiophenyl)methyleneimine containing a thioether and two pyridine donors, are described. Also, the mixed ligand complexes [Cu(pmtpm)(diimine)](ClO4)2 (2-5), where the diimine is 2,2'-bipyridine (bpy) (2), 1,10-phenanthroline (phen) (3), 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) (4) or dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) (5), have been isolated and studied. The X-ray crystal structures of the complexes 1, [Cu(pmtpm)(2,9-dmp)](ClO4)2 4 and 6 have been successfully determined. The complex 1 possesses a trigonal bipyramidal distorted square based pyramidal (TBDSBP) coordination geometry in which three corners of the square plane are occupied by two nitrogens and thioether s of pmtpm ligand and the remaining equatorial and the axial positions by two chloride ions. The complex 4 contains a CuN4S chromophore also with a TBDSBP coordination geometry in which two nitrogens and the thioether sulfur of pmtpm ligand occupy three corners of the square plane. One of the two nitrogens of 2,9-dmp ligand is equatorially coordinated and the other axially to copper. On the other hand, the complex 6 is found to possess a square based pyramidal distorted trigonal bipyramidal (SPDTBP) coordination geometry. The CuN2S trigonal plane in it is comprised of the pyridine and imine nitrogens and the thioether sulfur of the pmtpm ligand. The pyridine nitrogens of the ligand occupy the axial positions and the second thioether sulfur remains uncoordinated. On long standing in acetonitrile solution the mixed ligand complexes 2 and 3 undergo ligand disproportionation to provide the corresponding bis-complexes of bpy and phen, respectively, and 6. The electronic and EPR spectral parameters and the positive redox potential of complex 4 are consistent with the equatorial location of the thioether sulfur in the square-based coordination geometry around copper(II). On the other hand, the higher g|| and lower A|| values and lower E1/2 values for the complexes 2, 3 and 5 are consistent with the axial coordination of the thioether sulfur. Also, the Cu(II)/Cu(I) redox potentials increase with increase in number of aromatic rings of the diimine ligand. The steric and electronic effects of the bidentate diimine ligands in orienting the thioether coordination to axial or equatorial position are discussed

Selectivity of a thiosemicarbazonatocopper(II) complex towards duplex RNA. Relevant noncovalent interactions both in solid state and solution

Thiosemicarbazones and their metal derivatives have long been screened as antitumor agents, and their interactions with DNA have been analysed. Herein, we describe the synthesis and characterization of compounds containing [CuL]+ entities (HL = pyridine-2-carbaldehyde thiosemicarbazone) and adenine, cytosine or 9-methylguanine, and some of their corresponding nucleotides. For the first time, crystal structures of adenine- and 9-methylguanine-containing thiosemicarbazone complexes are reported. To the best of our knowledge, the first study on the affinity thiosemicarbazone–RNA is also provided here. Experimental and computational studies have shown that [CuL(OH2)]+ entities at low concentration intercalate into dsRNA poly(rA)·poly(rU) through strong hydrogen bonds involving uracil residues and π–π stacking interactions. In fact, noncovalent interactions are present both in the solid state and in solution. This behaviour diverges from that observed with DNA duplexes and creates an optimistic outlook in achieving selective binding to RNA for subsequent possible medical applications.Obra Social “la Caixa” (OSLC-2012-007), Ministerio de Economía y Competitividad and FEDER funds (CTQ2013-48937-C2-1-P, CTQ2015-70371- REDT, MAT2012-34740 and CTQ2014-58812-C2-2-R), Junta de Castilla y León (BU237U13), the Basque Government (IT-779- 13), Gerencia Regional de Salud, Consejería de Sanidad, Junta de Castilla y León (GRS 1023/A/14 and GR172)

Distortion Isomerism of Cu(II) Chloride Adducts with Bis(2-benzimidazolyl)ethane. Synthesis, Characterization, X-ray Structures and Spectroscopy of Four Different Isomers

Metals in Catalysis, Biomimetics & Inorganic Material