Simultaneous determination of chromium (III) and copper (II) by using derivative spectrophotometry with MEDTA

The application of derivative spectrophotometry to the simultaneous determination of chromium (III) and copper (II) with MEDTA is described. The procedure is suitable for concentrations of 0.40–2.60 mg ml^–1 of chromium (III) and 0.15–0.60 mg ml^–1 of copper (II). The main interferences, both anionic and cationic, are easily eliminated. The method was applied to different aqueous matrices. It was compared with an atomic absorption method and good results were obtained. Received: 12 June 1996 / Revised: 30 July 1996 / Accepted: 2 August 1996     

Quelques considérations sur la structure électronique du naphtalène

Theπ electronic structure of naphtalene is studied, using a semi-empirical approximation for coulombic and resonance integrals; forH andS (H, hamiltonian;S, overlap) the complete matrices are adopted, together withKohlrausch's nuclear effective charges. A non uniform charge distribution is obtained, with charge accumulation at the tertiary carbons. Bond orders between non neighboring atoms indicate contributions to the fundamental state from other structures besides the classical ones. A comparative study of the obtained interatomic distances is carried. It is shown that [H, S]=0 is not a sufficient condition for the identity of the bond orders for the fundamental state calculated with and without overlap.     

Supercritical fluid extraction of polycyclic aromatic hydrocarbons from liver samples and determination by HPLC-FL

An extraction/clean-up procedure by SFE was developed for isolating PAHs from liver samples for subsequent HPLC-FL determination of ten PAHs in the enriched extract. Recoveries (90-115%) and RSD % (< or =7.7) were satisfactory. When applied to 11 samples of bird of prey (Tyto alba) protected species and classified of special interest, from the Galicia (Northwest to Spain), benzo[ghi]perylene and indeno[1,2,3-cd]pyrene were undetectable; chrysene and benzo[a]pyrene are only detected in one sample; benzo[a]anthracene and benzo[k]fluoranthene are only quantified in one sample and benzo[b]fluoranthene in two samples. The other PAHs, anthracene, fluoranthene and pyrene are present in almost all the samples.     

Reactivity of amino acids in nitrosation reactions and its relation to the alkylating potential of their products

Nitrosation reactions of amino acids with an -NH(2) group [namely, six alpha-amino acids (glycine, alanine, alpha-aminobutyric acid, alpha-aminoisobutyric acid, valine, and norvaline); two beta-amino acids (beta-alanine and beta-aminobutyric acid), and one gamma-amino acid (gamma-aminobutyric acid)] were studied. Nitrosation was carried out in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r = k(3)(exp)[amino acid][nitrite](2), with a maximum k(3)(exp) value in the 2.3-2.7 pH range. The existence of an isokinetic relationship supports the argument that all the reactions share a common mechanism. A nitrosation mechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acids with a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. The finding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that the yield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii) Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity (k(3)()(exp)) [alpha-amino acids > beta-amino acids > gamma-amino acids] is the same as that found in a previous work for the alkylating potential of lactones formed from nitrosation products of the same amino acids. This implies that the nitrosation reactions of the most common natural amino acids are the most efficient precursors of the most powerful alkylating agents. (iv) The order of magnitude (10(7)-10(8) M(-1) s(-1)) of the bimolecular rate constants of nitrosation shows that such reactions occur through an encounter process.     

Diverse evolution of [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu-S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 2, 3) metalloligands in CH(2)Cl(2)

The nucleophilicity of the [Pt(2)S(2)] core in [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu-S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 3, dppp (1); n = 2, dppe (2)) metalloligands toward the CH(2)Cl(2) solvent has been thoroughly studied. Complex 1, which has been obtained and characterized by X-ray diffraction, is structurally related to 2 and consists of dinuclear molecules with a hinged [Pt(2)S(2)] central ring. The reaction of 1 and 2 with CH(2)Cl(2) has been followed by means of (31)P, (1)H, and (13)C NMR, electrospray ionization mass spectrometry, and X-ray data. Although both reactions proceed at different rates, the first steps are common and lead to a mixture of the corresponding mononuclear complexes [Pt[Ph(2)P(CH(2))(n)PPh(2)](S(2)CH(2))], n = 3 (7), 2 (8), and [Pt[Ph(2)P(CH(2))(n)PPh(2)]Cl(2)], n = 3 (9), 2 (10). Theoretical calculations give support to the proposed pathway for the disintegration process of the [Pt(2)S(2)] ring. Only in the case of 1, the reaction proceeds further yielding [Pt(2)(dppp)(2)[mu-(SCH(2)SCH(2)S)-S,S']]Cl(2) (11). To confirm the sequence of the reactions leading from 1 and 2 to the final products 9 and 11 or 8 and 10, respectively, complexes 7, 8, and 11 have been synthesized and structurally characterized. Additional experiments have allowed elucidation of the reaction mechanism involved from 7 to 11, and thus, the origin of the CH(2) groups that participate in the expansion of the (SCH(2)S)(2-) ligand in 7 to afford the bridging (SCH(2)SCH(2)S)(2-) ligand in 11 has been established. The X-ray structure of 11 is totally unprecedented and consists of a hinged [(dppp)Pt(mu-S)(2)Pt(dppp)] core capped by a CH(2)SCH(2) fragment.     

TOPS-MODE based QSARs derived from heterogeneous series of compounds. Applications to the design of new herbicides

A new application of TOPological Sub-structural MOlecular DEsign (TOPS-MODE) was carried out in herbicides using computer-aided molecular design. Two series of compounds, one containing herbicide and the other containing nonherbicide compounds, were processed by a k-Means Cluster Analysis in order to design the training and prediction sets. A linear classification function to discriminate the herbicides from the nonherbicide compounds was developed. The model correctly and clearly classified 88% of active and 94% of inactive compounds in the training set. More specifically, the model showed a good global classification of 91%, i.e., (168 cases out of 185). While in the prediction set, they showed an overall predictability of 91% and 92% for active and inactive compounds, being the global percentage of good classification of 92%. To assess the range of model applicability, a virtual screening of structurally heterogeneous series of herbicidal compounds was carried out. Two hundred eighty-four out of 332 were correctly classified (86%). Furthermore this paper describes a fragment analysis in order to determine the contribution of several fragments toward herbicidal property; also the present of halogens in the selected fragments were analyzed. It seems that the present TOPS-MODE based QSAR is the first alternate general "in silico" technique to experimentation in herbicides discovery.     

Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

---

Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

Singlet oxygen generation versus O–O homolysis in phenyl-substituted anthracene endoperoxides investigated by RASPT2, CASPT2, CC2, and TD-DFT methods

Peptidylarginine deiminase 4 (PAD4), also known as protein arginine deiminase 4, performs a post-translational deimination that converts arginine to citrulline. The dysregulation of PAD4 has been implicated in a number of diseases, including rheumatoid arthritis (RA) and cancer. This makes PAD4 an important therapeutic target. To develop small-molecule inhibitors as potential treatments, it is advantageous if the catalytic mechanism is well understood. The protonation states of the active site residues, which have long been under controversy, have a direct impact on the catalytic mechanism. Two competing mechanisms are under investigation in the current literature. The first is a reverse protonation mechanism that depends on the active site histidine and cysteine existing as an ion pair. The second is a substrate-assisted mechanism that depends on the active site histidine and cysteine being neutral. This study uses the semimicroscopic protein dipoles Langevin dipoles (PDLD/S) linear response approximation method in the MOLARIS software package to calculate the change in solvation energy of moving the residue from water to the protein interior, and then using that information to assess the protonation states of the active site residues of PAD4. Results from these calculations suggest that in the enzyme–substrate complex of PAD4, the cysteine and histidine are protonated and deprotonated, respectively, and are therefore both neutral, analogous to the proposed protonation states of the active site residues in the Michaelis complex in the substrate-assisted mechanism.