NMR Investigation of the Interaction of Three Non-Steroidal Anti-Inflammatory Drugs with Human Serum Albumin

The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to-protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction.     

Synthesis,structure, spectral and coordination properties of a crown ether derivative of 1,3-indandione. A new structural evidence for the versatile reactivity of 2-acetyl-1,3-indandione

The current study describes the synthesis of a new 1,3-indandione derivative with conjugated N-phenylaza-15-crown-5 moiety (4). The crystal structure of compound 4 was solved and its optical properties were studied in various solvents and in presence of alkaline and alkaline-earth metal ions. Quantum chemical (DFT) methods were employed to describe the structure and the optical properties of the studied compound and its complexes. The obtained results indicated that the synthesis of compound 4 using acid-catalyzed aldol reaction between 2-acetyl-1,3-indandione and the corresponding aldehyde is accompanied with an unexpected deacetylation step. In this way, the N-phenylaza-15-crown-5 moiety is directly conjugated with the 1,3-indandione fragment, known as a very strong electron acceptor. Therefore, the absorption spectra of 4 are only slightly influenced by complexation with Ba²⁺ and Sr²⁺ ions.     

Biomimetic surface modifications based on the cyanobacterial iron chelator anachelin

Siderophores are natural iron chelators that have been evolutionarily selected to bind to Fe ions with very high binding constants. We utilize these unique properties to bind to metal oxide surfaces using a fragment of the cyanobacterial siderophore anachelin. The resulting poly(ethylene glycol) conjugate forms stable adlayers on TiO2 as has been shown by variable angle spectroscopic ellipsometry and X-ray photoelectron spectroscopy. Moreover, these coated surfaces are highly protein-resistant against the adsorption of full human serum.     

Colored operads,series on colored operads,and combinatorial generating systems

We introduce bud generating systems, which are used for combinatorial generation. They specify sets of various kinds of combinatorial objects, called languages. They can emulate context-free grammars, regular tree grammars, and synchronous grammars, allowing us to work with all these generating systems in a unified way. The theory of bud generating systems uses colored operads. Indeed, an object is generated by a bud generating system if it satisfies a certain equation in a colored operad. To compute the generating series of the languages of bud generating systems, we introduce formal power series on colored operads and several operations on these. Series on colored operads are crucial to express the languages specified by bud generating systems and allow us to enumerate combinatorial objects with respect to some statistics. Some examples of bud generating systems are constructed; in particular to specify some sorts of balanced trees and to obtain recursive formulas enumerating these.     

Subagging for credit scoring models

The logistic regression framework has been for long time the most used statistical method when assessing customer credit risk. Recently, a more pragmatic approach has been adopted, where the first issue is credit risk prediction, instead of explanation. In this context, several classification techniques have been shown to perform well on credit scoring, such as support vector machines among others. While the investigation of better classifiers is an important research topic, the specific methodology chosen in real world applications has to deal with the challenges arising from the real world data collected in the industry. Such data are often highly unbalanced, part of the information can be missing and some common hypotheses, such as the i.i.d. one, can be violated. In this paper we present a case study based on a sample of IBM Italian customers, which presents all the challenges mentioned above. The main objective is to build and validate robust models, able to handle missing information, class unbalancedness and non-iid data points. We define a missing data imputation method and propose the use of an ensemble classification technique, subagging, particularly suitable for highly unbalanced data, such as credit scoring data. Both the imputation and subagging steps are embedded in a customized cross-validation loop, which handles dependencies between different credit requests. The methodology has been applied using several classifiers (kernel support vector machines, nearest neighbors, decision trees, Adaboost) and their subagged versions. The use of subagging improves the performance of the base classifier and we will show that subagging decision trees achieve better performance, still keeping the model simple and reasonably interpretable.     

Synthesis of nickel sulfide and nickel–iron sulfide nanoparticles from nickel dithiocarbamate complexes and their photocatalytic activities

[ Ni(dtc)₂] (dtc = N-(pyrrole-2-ylmethyl)-N-thiophenemethyldithiocarbamate ( 1 ), N-methylferrocenyl-N-(2-phenylethyl)dithiocarbamate ( 2 ), N-furfuryl-N-methylferrocenyldithiocarbamate ( 3 ), and (N-[pyrrole-2-ylmethyl]-N-thiophenemethyldithiocarbamato-S,S′)(thiocyanato-N)(triphenylphosphine)nickel(II) ( 4 ) complexes were prepared and characterized by elemental analysis, infrared, ultraviolet–visible, and nuclear magnetic resonance (¹H and ¹³C) spectroscopies. The data were consistent with the formation of square planar nickel(II) complexes, which was confirmed by single-crystal X-ray diffraction studies on 2 and 4 . Fe···Fe interactions exhibited by complex 2 led to supramolecular aggregation. The structure of 4 reveals intermolecular and intramolecular C-H···Ni anagostic interactions. The anion-sensing properties of 2 were studied with halide ions by cyclic voltammetry. It was observed that 2 acts as sensor for bromide. Complexes 1 , 2 , and 3 , were utilized to prepare nickel sulfide, nickel–iron sulfide-1, and nickel–iron sulfide-2, respectively. The composition, structure, morphology, and optical properties of nickel sulfide and nickel–iron sulfides were examined using powder X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy, ultraviolet–visible, fluorescence, and infrared spectroscopy. Powder X-ray diffraction patterns of nickel sulfide, nickel–iron sulfide-1, and nickel–iron sulfide-2 indicate the formation of orthorhombic Ni₉S₈, cubic NiFeS₂, and cubic Ni₂FeS₄, respectively. The photocatalytic activities of as-prepared nickel sulfide and nickel–iron sulfide-1 nanoparticles were investigated for photodegradation of methylene blue and rhodamine-B under ultraviolet irradiation. Nickel–iron sulfide-1 nanoparticles show slightly higher photodegradation efficiency compared with the nickel sulfide nanoparticles.     

Acid-catalysed,nucleophile-catalysed and thermal decomposition of 2-amino-3-(2′,2′-dimethylaziridino)-1,4-naphthoquinone

The course of the thermal, acid-catalysed and iodide-catalysed decomposition of 2-amino-3-(2′,2′-dimethylaziridino)-1,4-naphthoquinone (III) was investigated. Thermal and iodide-catalysed decompositions gave mainly 2,3-diamino-1,4-naphthoquinone (VI) and 2-amino-3-(2′-methylallylamino)-1,4-naphthoquinone (V) together with low amounts of 2,2-dimethyl-1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline (IV) and 2-isopropyl-1H-naphthoimid-azole-4,9-dione (VII). The acid catalysed isomerization of the aziridinonaphthoquinone III with halohydric acids or with acetic acid readily gave the opening of the aziridine ring; the corresponding salts of 2-amino-3-(2′-haloisobutylamino)-1,4-naphthoquinones (VIIIa-c) and 2-amino-3-(2′-acetoxyisobutylamino)-1,4-naphthoqunone (X) were formed by cleavage of the carbon-nitrogen bond at the substituted carbon atom. Hypotheses on the mechanism of these reactions are given.     

Thermal decomposition of 2-amino-3-aziridino-1,4-naphthoquinones

The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated. In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxaline-5,10-diones (IIIa-g) with complete stereospecificity. The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f). In the case of 2-amino-3-(2′-phenyl-3′-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-naphtho-imidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzo[g]quinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzo[g]quinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetra-hydro-2-phenyl-3-ethyl-5-iminonaphtho[1,2-b]oxazin-6-one (IX) also occurred. Hypotheses concerning the mechanism and the steric course of this reaction are given. The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzo[g]quinoxalines.     

Conformationally restricted analogues of both (S)-β-homoserine and (S)-aspartic acid from chiral 3-acylamino pyrrolidin-2-ones

Starting from chiral 3,4-trans-disubstituted pyrrolidin-2-ones 11a and 11b, obtained from a Baylis-Hillman adduct, conformationally restricted analogues of both (S)-β-homoserine, 17, and (S)-aspartic acid, 21, were synthesized, respectively, and these compounds are suitable either for introduction in peptidomimetics or for synthesis of novel β-foldamers.