Marco Pasquali

Chemistry and Biology of Two Novel Gold(I) Carbene Complexes as Prospective Anticancer Agents

Two novel gold carbene compounds, namely, chlorido (1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (1) and bis(1-butyl-3-methyl-imidazole-2-ylidene) gold(I) (2), were prepared and characterized as prospective anticancer drug candidates. These compounds consist of a gold(I) center linearly coordinated either to one N-heterocyclic carbene (NHC) and one chloride ligand (1) or to two identical NHC ligands (2). Crystal structures were solved for both compounds, the resulting structural data being in good agreement with expectations. We wondered whether the presence of two tight carbene ligands in 2 might lead to biological properties distinct from those of the monocarbene complex 1. Notably, in spite of their appreciable structural differences, these two compounds manifested similarly potent cytotoxic actions in vitro when challenged against A2780 human ovarian carcinoma cells. In addition, both were able to overcome resistance to cisplatin in the A2780R line. Solution studies revealed that these gold carbene complexes are highly stable in aqueous buffers at physiological pH. Their reactivity with proteins was explored: no adduct formation was detected even upon a long incubation with the model proteins cytochrome c and lysozyme; in contrast, both compounds were able to metalate, to a large extent, the copper chaperone Atox-1, bearing a characteristic CXXC motif. The precise nature of the resulting gold-Atox-1 adducts was elucidated through ESI-MS analysis. On the basis of these findings, it is proposed that the investigated gold(I) carbene compounds are promising antiproliferative agents warranting a wider pharmacological evaluation. Most likely these gold compounds produce their potent biological effects through selective metalation and impairment of a few crucial cellular proteins.

Comparison of Multi-Criteria Scheduling Techniques

We propose a novel schedule-based approach for scheduling a continuous stream of batch jobs on the machines of a computational Grid. Our new solutions represented by dispatching rule Earliest Gap-Earliest Deadline First (EG-EDF) and Tabu search are based on the idea of filling gaps in the existing schedule. EG-EDF rule is able to build the schedule for all jobs incrementally by applying technique which fills earliest existing gaps in the schedule with newly arriving jobs. If no gap for a coming job is available EG-EDF rule uses Earliest Deadline First (EDF) strategy for including new job into the existing schedule. Such schedule is then optimized using the Tabu search algorithm moving jobs into earliest gaps again. Scheduling choices are taken to meet the Quality of Service (QoS) requested by the submitted jobs, and to optimize the usage of hardware resources. Proposed solution is compared with FCFS, EASY backfilling, and Flexible backfilling. Experiments shows that EG-EDF rule is able to compute good assignments, often with shorter algorithm runtime w.r.t. the other queue-based algorithms. Further Tabu search optimization results in higher QoS and machine usage.

A simple synthesis and crystal structure of the dinuclear diphosphido-bridged palladium(I) complex [Pd(PtBu2H)(μ-PtBu2)]2

Abstract UV irradiation of Pd(P t Bu 3 ) 2 in n-hexane or THF gives the diamagnetic dinuclear complex [Pd(P t Bu 2 H)(μ-P t Bu 2 )] 2 , 2-methylpropene, and hydrogen. The complex was also obtained from the reaction of Pd(η 5 -C 5 H 5 ) (η 3 -C 3 H 5 with P t Bu 2 H in toluene. Its crystal and molecular structure were determined by an X-ray diffraction study. Each Pd bears a terminal P t Bu 2 H ligand and the two metal centers are bridged by two phosphido ligands.

Oxidative addition of OH bond to a metal centre: synthesis and crystal structure of trans-(PhO)(H)Pd(PCy3)2·PhOH

Abstract (Cy3P)2Pd (Cy = C6H11) reacts with PhOH in toluene to give the phenoxopalladium(II) hydride derivative trans-(PhO)(H)Pd(PCy3)2·PhOH; the crystal structural study has established that the oxygen of the phenoxy group forms a hydrogen bridge with an uncoordinated phenol molecule, and has allowed direct location of the hydride atom (Pd&.sbnd;H, 1.57(2) A).

Backfilling Strategies for Scheduling Streams of Jobs On Computational Farms

This paper presents a set of strategies for scheduling a stream of batch jobs on the machines of a heterogeneous computational farm. Our proposal is based on a flexible backfilling, which schedules jobs according to a priority assigned to each job submitted for execution. Priority values are computed as a result of a set of heuristics whose main goal is to improve resources utilization and to meet the job QoS requirements. The heuristics consider job deadlines, estimated execution time and aging of the jobs in the scheduling queue. Furthermore, the set of software licenses required by a job is also considered. The different proposals have been compared through simulations. Performance figures show the applicability of our approach.

A job scheduling framework for large computing farms

In this paper, we propose a new method, called Convergent Scheduling, for scheduling a continuous stream of batch jobs on the machines of large-scale computing farms. This method exploits a set of heuristics that guide the scheduler in making decisions. Each heuristics manages a specific problem constraint, and contributes to carry out a value that measures the degree of matching between a job and a machine. Scheduling choices are taken to meet the QoS requested by the submitted jobs, and optimizing the usage of hardware and software resources. We compared it with some of the most common job scheduling algorithms, i.e. Backfilling, and Earliest Deadline First. Convergent Scheduling is able to compute good assignments, while being a simple and modular algorithm.

The reactivity of Pd(PtBu3)2 towards the oxonium ion. Crystal structure of trans-[(tBu3P)2 Pd(H)(CH3CN)]BPh4

The reaction of Pd(PtBu3)2 with the strong acids H3O+X−, (X = BF3OH, BF4), gives the thermally unstable hydrides trans-[(tBu3P)2Pd(H)(H2O)]X. The thermally stable hydrides trans-[(tBu3P)2Pd(H) (CH3CN)]X were obtained by substitution of the water molecule by CH3CN. The reaction of the aquo-hydrides with CO, yielding [Pd(CO)(PtBu3)]2 and the crystal structure of trans[[(tBu3P)2Pd(H) (CH3CN)]BPh4 are also reported.

Oxidation of palladium(I) dimers: Formation and X-ray crystal structure of [(Me3P)2Pd(μ-OH)2Pd(PMe3)2](CF3SO3)2

Abstract Air oxidation of the phosphido-bridged Pd(I) dimer Pd2(μ-PtBu2)(PMe3)4]CF3SO3) gives the hydroxo-bridged Pd(II) dinuclear derivative [(ME3P)2Pd(μ-OH)2Pd(PMe2)2](CF3SO2 (1) with a low yield. The same cation was obtained with a high yield by the reaction of [PdCl2(PMe3)2] with silver nitrate in wet acetone. The crystal structure of 1 was determined.

Reactivity of cationic molybdenum(II) complexes. Part 1. Hydride reduction of the 18 electron complexes [Mo(CO)3(η-C5Me5)L]+[L = PPh3 or P(OMe)3] and isolation of the thermally stable formyl complex cis-[Mo(CO)2(η-C5Me5){P(OMe)3}(CHO)]. Crystal structure of [Mo(CO)3(η-C5Me5)(PPh3)]BF4·0.5MeOH

The compound [Mo(CO)3(η-C5Me5)]BF4 reacts with π acids, L [L = PPh3, P(OMe)3, CO, or p-MeC6H4NC], giving the 18 electron cations [Mo(CO)3(η-C5Me5)L]+. The complex [Mo(CO)3(η-C5Me5)(PPh3)]BF4(1) has been characterized by a single-crystal X-ray diffraction study. The reaction of (1) with one equivalent of Na[BH4] gives the neutral metal formyl complex [Mo(CO)2(η-C5Me5)(PPh3)(CHO)], (2), which, in solution, converts to [MoH(CO)3(η-C5Me5)] above –40 °C. If [Mo(CO)3(η-C5Me5){P(OMe)3}]BF4, (3), is used instead of (1), the reduction in methanol solution with Na[BH4] allows isolation of the thermally stable cis-[Mo(CO)2(η-C5Me5){P(OMe)3}(CHO)], (4). Thermal decomposition of (4) in methanol solution at room temperature is slow and gives cis-[MoH(CO)2(η-C5Me5){P(OMe)3}]. This result emphasizes that the great difference observed in the thermal stability of complexes (2) and (4) is attributable to different decomposition pathways.

Synthesis, molecular and electronic structure of the first homoleptic complex of platinum with a secondary phosphine

Abstract The reaction of CpPt(η 3 -C 3 H 5 ) with PBu 1 2 H in acetone gives the Pt(0) mononuclear derivative Pt(PBu 1 2 H) 3 ( 1 ). As demonstrated by variable temperature 31 P 1 H NMR spectra, complex 1 dissociates one of the phosphines in toluene solution affording the 14e − Pt(PBuP 1 2 H) 2 . The crystal and molecular structure of 1 was solved by X-ray diffraction which reveals a trigonal planar disposition of the phosphine molecules (C 24 H 57 P 3 Pt: hexagonal, space group P6 3 /m, a = b = 10.4150(11), c = 16.263(3) A , Z = 2 ). The PH hydrogen atoms were located in the Fourier map and were found to lie in the coordination plane, with the t-butyl substituents in an eclipsed configuration. Ab initio and molecular dynamics calculations essentially confirm the structure obtained by X-ray diffraction. An agostic PtHP interaction was excluded and the geometry was explained in terms of steric interactions.