The versatile chemistry of niobium pentachloride with aliphatic amines: Aminolysis, metal reduction and C–H activation

The reactions of NbCl5 with limited amounts (1-2 molar equivalents) of a series of primary, secondary and tertiary amines were investigated in dichloromethane as solvent. The 1:1 reaction of NbCl5 with NHEt2 cleanly afforded an equimolar mixture of [NbCl4(NEt2)]2, 1, and [NH2Et2][NbCl6], 2a; the former product constitutes the first example of structurally characterized Nb(V) chlorido-amido complex. The ammonium salts [NH3nPr][NbCl6], 2b, and [NH2iPr2][NbCl6], 2c, were isolated in 20-30% yields from the 1:1 reactions of NbCl5 with NH2nPr and NHiPr2, respectively. Cα-H bond activation and Nb(V) to Nb(IV) reduction took place in the reactions of NbCl5 with NR3 (R = Bz, Et; Bz = CH2Ph). The iminium salt [(PhCH2)2N=CHPh][NbCl6], 3, and the ammonium ion [NH(CH2Ph)3]+ were identified as the prevalent species generated from the 1:1 NbCl5/NBz3 interaction. [NHEt3][NbCl6], 4, and [NHEt3]2[NbCl6], 5, were isolated in moderate yields from, respectively, the 1:1 and 1:2 molar reactions of NbCl5 with NEt3. The solid state structures of 1, 2a, 3, 4 and 5 were ascertained by single crystal X-ray studies

Synthesis and DNA binding tests of a fluorescent pyrene bearing a Pt(II) pyridineimino complex

Despite the long time gone respect to the discovery of cis-platinum anticancer activity, still a huge amount of research is devoted to the design of new Pt(II) complexes with enhanced biological activity [1-3]. The here presented work concerns the synthesis of a fluorescent pyridinimino platinum(II) complex, where the presence of a cis-platinum moiety linked to an extended aromatic residue could provide interesting properties as for binding to biosubstrates. In fact, covalent Pt(II) binding can occur, which would be strengthened by the anchoring offered by possible intercalation in nucleic acids of the pyrene fragment. Antiproliferative properties have been described for some pyridinimino [4] and pyridinamino [5] platinum(II) complexes. Moreover, similar bifunctional systems have already been tested with interesting performances [7,8]. The chelating iminopyridine ligand was prepared by a condensation reaction between pyridine-2-carboxyaldehyde and the suitably O-alkylated aminoalcohol. The platinum complex was then synthesized starting from cis-[PtCl2(DMSO)2], and purified by crystallization. The pure complex (elemental analysis) was spectroscopically (IR, 1H-, 13C and 195Pt NMR) characterized. It is well soluble in DMSO and in DMSO/H2O mixtures, where its stability was checked by 1H- and 195Pt NMR. The absorbance and fluorescence optical features of the dye were also checked. Afterwards, the target Pt(II) complex was let interact with natural double stranded DNA to check its reactivity towards this biosubstrate. Spectrophotometric and spectrofluorometric titrations show that the binding does indeed occur. As for absorbance data, hypochromic and bathochromic effects suggest intercalative binding. However, the absence of a defined isosbestic point indicates multiple equilibria. Interestingly and in agreement with this observation, the light emission behavior of the dye/DNA system is complex. Opposite fluorescence change trends are observed at different temperatures, likely related to a different contribution of DNA-templated dye aggregation. Under the (until now) explored conditions, the binding is so strong to turn to be quantitative. Further experiments are ongoing to better enlighten the binding mechanism. References: [1] S. X. Chong, S. C. F. Au-Yeung, K. K. W. To, Current Medicinal Chemistry 2016, 23(12), 1268-12. [2] L. Cai, C. Yu, L. Ba, Q. Liu, Y. Qian, B. Yang, C. Gao, Applied Organometallic Chemistry 2018, 32(4). [3] M. Hanif, C. G. Hartinger, Future Medicinal Chemistry 2018, 10(6), 615-617. [4] B. A. Miles, A. E. Patterson, C. M. Vogels, A. Decken, J. C. Waller, P. Jr. Morin, S. A. Westcott, Polyhedron 2016, 108, 23-29. [5] S. Karmakar, K. Purkait, S. Chatterjee, A. Mukherjee, Dalton Trans. 2016, 45, 3599-3615. [6] S. Hochreuther, R. van Eldik, Inorg. Chem., 2012, 51 (5), 3025-3038. [7] C. Bazzicalupi, A. Bencini, A. Bianchi, T. Biver, A. Boggioni, S. Bonacchi, A. Danesi, C. Giorgi, P. Gratteri, A. Marchal Ingraín, F. Secco, C. Sissi, B. Valtancoli, M. Venturini, Chemistry – A European Journal 2008, 14(1), 184-196. [8] S. Biagini, A. Bianchi, T. Biver, A. Boggioni, I.V. Nikolayenko, F. Secco, M. Venturini, Journal of Inorganic Biochemistry 2011, 105, 558-562

Weight Loss Expectations in Obese Patients and Treatment Attrition: An Observational Multicenter Study

Objective: To investigate the influence of weight loss expectations (expected 1-year BMI loss, dream and maximum acceptable BMI) on attrition in obese patients seeking treatment. Research Methods and Procedures: Obese subjects (1785; 1393 women; median age, 46 years; median BMI, 36.7 kg/m2) seeking treatment in 23 medical Italian centers were evaluated. Baseline diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating, and body image dissatisfaction were tested at baseline by self-administered questionnaires (Symptom Check List-90, Binge Eating Scale, and Body Uneasiness Test). Attrition and BMI change at 12 months were prospectively recorded. Results: At 12 months, 923 of 1785 patients (51.7%) had discontinued treatment. Compared with continuers, dropouts had a significantly lower age, a lower age at first dieting, lower dream BMI, a higher expected 1-year BMI loss, and a higher weight phobia. At logistic regression analysis, the strongest predictors of attrition at 12 months were lower age and higher expected 1-year BMI loss. The risk of drop-out increased systematically for unit increase in expected BMI loss at 12 months (hazard ratio, 1.12; 95% confidence interval, 1.04 to 1.20; p 0.0018). The risk was particularly elevated in the first 6 months. Discussion: Baseline weight loss expectations are independent cognitive predictors of attrition in obese patients entering a weight-losing program; the higher the expectations, the higher attrition at 12 months. Unrealistic weight goals should be tackled at the very beginning of treatment

Electromyographic signature of isometric squat in the highest refuge in Europe

Reports of electromyography during hypoxic exercise are contrasting, due to protocol and muscle diversity. This work aimed to investigate alterations in muscle activation and myoelectrical fatigue during exercise at high-altitude in those muscles primarily involved in trekking. Twelve young adults balanced by gender and age were tested at low (1,667 m) and high (4,554 m, "Capanna Margherita", Italy) altitude, during an isometric squat lasting 60 seconds. High-density surface electromyography was performed from the quadriceps of right limb. The root mean square (RMS), median frequency with its slope, and muscle fiber conduction velocity (MFCV) were computed. Neither males nor females showed changes in median frequency (Med: 36.13 vs 35.63 Hz) and its slope (Med: -9 vs -12 degree) in response to high-altitude trekking, despite a great inter-individual heterogeneity, nor differences were found for MFCV. RMS was not significantly equivalent, with greater values at low altitude (0.385 ± 0.104 mV) than high altitude (0.346 ± 0.090 mV). Unexpected results can be due either to a postural compensation of the whole body compensating for a relatively greater effort or to the inability to support muscle activation after repeated physical efforts.  Interesting results may emerge by measuring simultaneously electromyography, muscle oxygenation and kinematics comparing trekking at normoxia vs hypoxia

Aumento dell'oee di assemblaggio - il caso del frutto dk in Elettrotecnica Rold spa

Il lavoro effettuato ha lo scopo di ridefinire il complesso delle attività organizzative, gestionali ed operative effettuate dall’unità produttiva della Rold per quel che riguarda il frutto DK, un blocca porta magnetico. L’INTRODUZIONE si sviluppa con la volontà di presentare il contesto di riferimento nel quale è stato svolto il lavoro, andando quindi a descrivere Rold, l’azienda all’interno della quale viene prodotto il frutto DK e Inema, la società di consulenza incaricata di ridefinire le attività collegate ad alcune fasi del processo produttivo del frutto DK, al fine di efficientare la realizzazione dei prodotti. Il CAPITOLO 1 richiama la letteratura di riferimento, sulla base della quale è stato sviluppato il progetto che viene esposto all’interno dell’elaborato. Il CAPITOLO 2 espone i risultati dell’analisi condotta per ricercare i problemi che affliggono la linea di produzione del frutto DK, determinandone una scarsa produttività. Il CAPITOLO 3 costituisce il cuore della tesi: presenta le possibili proposte di soluzione dei problemi individuati, scegliendo quelle che vengono ritenute più efficaci al raggiungimento dell’obiettivo di miglioramento di Rold. La CONCLUSIONE espone i risultati ottenuti attraverso le analisi svolte e le soluzioni proposte

Funzionalizzazione e studio dell'attività citotossica di nuovi complessi imminopiridinici di platino (II)

In questo lavoro di Tesi sono stati sintetizzati e caratterizzati nuovi complessi imminopiridinici di platino (II). La sintesi ha richiesto l’iniziale O-alchilazione del 2-(2-amminoetossi)-etanolo, facendo uso di appropriati bromuri arilmetilenici, seguita dalla condensazione con la piridin-2-carbaldeide per la formazione delle imminopiridine opportunamente funzionalizzate. Queste ultime sono state poi utilizzate come leganti chelanti del platino a partire da cis-[PtCl2(DMSO)2]. I nuovi complessi di Pt(II), di formula generale cis-[PtCl2(N⁀N’)], Figura 1, sono caratterizzati dalla presenza, sul legante, di residui aromatici di dimensione crescente (Ar: fenile; 2-naftile; 9-antracenile e 1-pirenile; Figura 1) e sono stati sintetizzati nell'ottica di creare sistemi in cui vi sia una possibile cooperazione, determinata dal centro metallico e dall'opportuno frammento aromatico, nell'interazione col DNA. L’imminopiridina contenente il residuo fenilico è stata utilizzata anche come legante per la sintesi del corrispondente cis-[PtBr2(N⁀N’)] nel quale due bromuri sostituiscono i cloruri nella sfera di coordinazione del metallo. La struttura di questo complesso, così come quella dell'analogo sistema clorurato, è stata confermata mediante studi di diffrazione a raggi X su cristallo singolo. I complessi cis-[PtCl2(N⁀N’)], Figura 1, sono stati testati in vitro su una serie di linee cellulari tumorali umane, sia sensibili che resistenti al cisplatino, per valutarne l’attività antiproliferativa. Le misure, svolte dal gruppo di ricerca della Prof.ssa Lisa Dalla Via, presso il Dipartimento di Scienze del Farmaco dell'Università degli Studi di Padova, mostrano risultati interessanti per quanto riguarda l’attività biologica nei confronti della linea cellulare resistente A-2780 cis. In particolare, il derivato contenente il frammento antracenilico si è dimostrato particolarmente attivo su questa linea cellulare con una citotossicità decisamente più alta rispetto a quella del cisplatino. Il risultato suggerisce che questo nuovo complesso di platino riesce, in qualche modo, ad aggirare uno o più dei meccanismi cellulari alla base della resistenza nei confronti del cisplatino. La presenza di gruppi aromatici sulla catena laterale del complesso chelato ha permesso, inoltre, di esaminare la possibile interazione col DNA utilizzando metodi spettrofotometrici e spettrofluorimetrici. Lo studio, condotto sul derivato contenente il residuo pirenilico e realizzato in collaborazione col gruppo di ricerca della Dott.ssa Tarita Biver presso il Dipartimento di Chimica e Chimica Industriale dell’Università di Pisa, ha indicato che nelle condizioni adottate si instaura un sistema complesso di interazioni col DNA caratterizzato da più possibili modalità di binding col polinucleotide

Biodegradable intraoperative system for bone infection treatment. II. In vivo evaluation

A biodegradable implant containing gentamicin sulphate for the prevention orr the treatment of bone infections was designed by using, as the polymer material, sodium alginate containing a high proportion of mannuronic sequences capable of forming a complex with the drug. By a crosslinking procedure with calcium ions, insoluble but biodegradable calcium alginate spheres were obtained and formed into a chain by means a surgical wire. To evaluate the implant effectiveness, the implant was inserted at the femur level of Wistar rats and gentamicin levels in plasma, bone and soft tissues were detected by microbiological assay. The gentamicin concentrations were found to be sufficiently high to control pathogens for at least 30 and 7 days in the bone and soft tissue, respectively, whereas plasma levels were low and detectable for only 1 day. The complete implant bioabsorption occurred within 8-10 days after implantation and no signs of rejection or inflammatory reactions were observed at the level of the surrounding tissues

Weight loss expectations in obese patients and treatment attrition: an observational multicenter study

Objective: To investigate the influence of weight loss expectations (expected 1-year BMI loss, dream and maximum acceptable BMI) on attrition in obese patients seeking treatment. Research Methods and Procedures: Obese subjects (1785; 1393 women; median age, 46 years; median BMI, 36.7 kg/m2) seeking treatment in 23 medical Italian centers were evaluated. Baseline diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating, and body image dissatisfaction were tested at baseline by self-administered questionnaires (Symptom Check List-90, Binge Eating Scale, and Body Uneasiness Test). Attrition and BMI change at 12 months were prospectively recorded. Results: At 12 months, 923 of 1785 patients (51.7%) had discontinued treatment. Compared with continuers, drop-outs had a significantly lower age, a lower age at first dieting, lower dream BMI, a higher expected 1-year BMI loss, and a higher weight phobia. At logistic regression analysis, the strongest predictors of attrition at 12 months were lower age and higher expected 1-year BMI loss. The risk of drop-out increased systematically for unit increase in expected BMI loss at 12 months (hazard ratio, 1.12; 95% confidence interval, 1.04 to 1.20; p = 0.0018). The risk was particularly elevated in the first 6 months. Discussion: Baseline weight loss expectations are independent cognitive predictors of attrition in obese patients entering a weight-losing program; the higher the expectations, the higher attrition at 12 months. Unrealistic weight goals should be tackled at the very beginning of treatment