Search

Objective: The correct identification of bipolar mixed states (MS) has important implications for clinical practice. The aim of the study was to define the multidimensional psychopathological structure of severe MS. To our knowledge, no factor analytical studies including only patients with MS, have been conducted before., Methods: In the first week of hospitalization, we evaluated by HAM-D-17, YMRS, BPRS and CGI, 202 Bipolar I inpatients with MS according to DSM-IV criteria referred for an ECT trial. A Principal-component analysis followed by Varimax rotation was performed on the 24-item BPRS. The relationships among different symptomatological subtypes and other clinical characteristics were explored., Results: Six interpretable factors were extracted: Psychotic-positive symptoms, Mania, Disorientation-Unusual Motor Behaviour, Depression, Negative Symptoms and Anxiety. On the basis of the highest z-scores, we found 6 "dominant" BPRS factor groups, that were statistically distinct and without significant overlap in the main symptomatological presentation. Only 29 (14.4%) of our patients could be described as "Dominant Manic" and 48 (23.8%) as "Dominant Depressive"; most importantly 125 (61.9%) were neither predominately-manic nor predominately-depressive. Variables including age, number of previous episodes, suicidal behavior and HAM-D and YMRS scores significantly differentiated the subtypes., Conclusion: At least in the most severe forms, MS appears to represent more than the superposition of affective symptoms of opposite polarity. Anxiety, perplexity, psychotic experiences, motor disturbances and grossly disorganized behavior seem to arise from protracted intra-episodic instability and presence of a drive state influencing the mood state and the emotional resonance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to identify different clinical subtypes in severe, treatment resistant bipolar mixed state (MS)., Method: The sample comprised 202 Bipolar I patients currently in MS referred for an Electro-convulsive Therapy (ECT) trial and evaluated in the first week of hospitalization and one week after the ECT course. Principal component factor analysis (PCA) followed by Varimax rotation was performed on 21 non-overlapping items selected from Hamilton rating-scale for depression (HAMD) and from Young mania rating-scale (YMRS) at baseline evaluation. Cluster subtypes derived from the factor scores were compared in clinical variables and final HAMD, YMRS, Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores., Results: The principal-component analysis extracted 6 interpretable factors explaining 55.9% of the total variance. Cluster analysis identified four groups, including respectively 63 (31.2%) subjects with Agitated-Irritable Mixed-Depression, 59 (29.2%) with Psychotic Mixed-Mania, 17 (8.5%) with Anxious-Irritable-Psychotic Mixed-Mania, and 63 (31.2%) with Retarded-Psychotic Mixed-Depression. The four clusters were statistically distinct and did not show significant overlap in the main symptomatological presentation. Cluster subtypes reported differences in number of past mood episodes, duration of the current episode, suicide attempts, lifetime comorbidity with panic and eating disorders, baseline and final rating-scale scores and rate of remission after ECT trial., Conclusions: Our study indicates that, at least in severe treatment resistant MS, multiple depressive and manic subtypes can be observed with substantial differences in terms of clinical presentation, course, associated comorbidities and treatment response., (© 2013 Elsevier B.V. All rights reserved.)

Deuterium labeling is a powerful way to gain mechanistic information in biology and chemistry. However, selectivity is hard to control experimentally, and labeled sites can be difficult to assign both in solution and in the solid state. Here we show that very selective high-deuterium contents can be achieved for the polyhydride ruthenium phosphine complex [RuH2(H2)2(PCyp3)2] (1) (PCyp3 = P(C5H9)3). The selectivity of the H/D exchange process is demonstrated by multinuclear NMR and neutron diffraction analyses. It has also been investigated through density functional theory (DFT) calculations. The reactions are performed under mild conditions at room temperature, and the extent of deuterium incorporation, involving selective C-H bond activation within the cyclopentyl rings of the phosphine ligands, can easily be tuned (solvent effects, D2 pressure). It is shown that D2 gas can inhibit the C-H/C-D exchange process.

This paper presents the synthesis and structural characterization of the unprecedented tris-phosphido-bridged compounds Pt3(μ-PBu(t)2)3X3 (X = Cl, Br, I), having only 42 valence electrons, while up to now analogous clusters typically have 44e(-). The new species were obtained by an apparent bielectronic oxidation of the 44e(-) monohalides Pt3(μ-PBu(t)2)3(CO)2X with the corresponding dihalogen X2. Their X-ray structures are close to the D3h symmetry, similarly to the 44e(-) analogues with three terminal carbonyl ligands. The products were also obtained by electrochemical oxidation of the same monohalides in the presence of the corresponding halide. In a detailed study on the formation of Pt3(μ-PBu(t)2)3I3, the redox potentials indicated that I2 can only perform the first monoelectronic oxidation but is unsuited for the second one. Accordingly, the 43e(-) intermediate [Pt3(μ-PBu(t)2)3(CO)2I](+) was ascertained to play a key role. Another piece of information is that, together with the fully oxidized product Pt3(μ-PBu(t)2)3I3, the transient 44e(-) species [Pt3(μ-PBu(t)2)3(CO)3](+) is formed in the early steps of the reaction. In order to extract detailed information on the formation pathway, involving both terminal ligand substitutions and electron transfer processes, a DFT investigation has been performed and all the possible intermediates have been defined together with their associated energy costs. The profile highlights many important aspects, such as the formation of an appropriate couple of 43e(-) intermediates having different sets of terminal coligands, and suitable redox potentials for the transfer of one electron. Optimizations of 45e(-) associative intermediates in the ligand substitution reactions indicate their possible involvement in the redox process with reduction of the overall energy cost. Finally, according to MO arguments, the unique stability of the 42e(-) phosphido-bridged Pt3 clusters can be attributed to the simultaneous presence of three terminal halides.

Two unprecedented oxygenated aaptaminoids have been synthesized starting from cheap and easily available 2,3-dihydroxybenzoic acid with the satisfactory overall yields of 31% and 34%. The key step of the procedure is the divergent thermic 5-exodig vs base-promoted 6-endodig cyclization of a 5-alkynylquinolinone derivative.

The relationship between anxiety and impulsivity is controversial and not well explored. The present investigation aims to compare impulsivity, measured by different rating tools, in patients with anxiety disorders vs. healthy controls. Forty-seven subjects with different anxiety disorders and 45 matched controls underwent diagnostic and symptomatological evaluations by the Mini Neuropsychiatric Interview (M.I.N.I) Plus 5.0, Bech-Raphaelsen Depression and Mania Scale (BRDMS), State-Trait Anxiety Inventory (STAI), Hypomania Check List (HCL-32) and the Clinical Global Impression (CGI); temperamental evaluations by the Questionnaire for the Affective and Anxious Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Modified (TEMPS-M), the Separation Anxiety Sensitivity Index (SASI), the Interpersonal Sensitivity Symptoms Inventory (ISSI); and psychometric and a neurocognitive evaluations of impulsivity using the Barratt Impulsiveness Scale (BIS-11) and the Immediate and Delayed Memory Task (IMT-DMT). Subjects with anxiety disorders were more impulsive than the controls in all the explored measures, with higher scores in symptomatological and, temperamental scales. Patients with anxiety disorders but without a lifetime history of comorbid major mood episodes had greater trait and state impulsivity than controls. Further investigations are needed to assess the extent to which impulsivity might or might not be directly related to the anxiety disorder., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Self-injurious behavior (SIB) associated with Tourette's syndrome (TS) is a severe neuropsychiatric condition that causes significant distress and can impair social functioning. The current treatment options for the condition include pharmacological, physical and psychosocial interventions. However, given the need for more effective interventions, especially for those patients who are unresponsive and/or intolerant to standard medications, further exploration of novel treatments is imperative. In this report, we present a case of SIB-TS that was successfully treated with pregabalin. The patient received 1-year of follow-up and was noted to have considerable improvement in symptoms. Although rigorous controlled studies are required, based on our case study, pregabalin may be a potential treatment option in some cases of SIB with TS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours., Patients and Methods: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail., Results: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians., Conclusions: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Squaraines have been known for many decades as very stable and versatile vis-NIR absorbing dyes. They have found applications for example as sensitizers in organic photovoltaics and photodetectors. The most common squaraine structure is the 1,3-regioisomer. Their 1,2-regioisomers are seldom mentioned and unanimously regarded as side products. A facile direct synthesis of 1,2-squaraines, highlighting the role played by reaction conditions and electronic factors, is described. The first electrochemical characterization of these dyes is also shown., (© 2011 American Chemical Society)

Low-temperature NMR measurements showed that protonolysis and deuterolysis by H(D)X acids on meta- and para-substituted dibenzylplatinum(II) complexes cis-[Pt(CH(2)Ar)(2)(PEt(3))(2)] (Ar = C(6)H(4)Y(-); Y = 4-Me, 1a; 3-Me, 1b; H, 1c; 4-F, 1d; 3-F, 1e; 4-Cl, 1f; 3-Cl, 1g; 3-CF(3), 1h) in CD(3)OD leads directly to the formation of trans-[Pt(CH(2)Ar)(PEt(3))(2)(CD(3)OD)]X (4a-4h) and toluene derivatives. The reaction obeys the rate law k(obsd) = k(H)[H(+)]. For CH(2)Ar = CH(2)C(6)H(5)(-), k(H) = 176 ± 3 M(-1) s(-1) and k(D) = 185 ± 5 M(-1) s(-1) at 298.2 K, ΔH(double dagger) = 46 ± 1 kJ mol(-1) and ΔS(double dagger) = -47 ± 1 J K(-1) mol(-1). In contrast, in acetonitrile-d(3), three subsequent stages can be distinguished, at different temperature ranges: (i) instantaneous formation of new benzylhydridoplatinum(IV) complexes cis-[Pt(CH(2)Ar)(2)(H)(CD(3)CN)(PEt(3))(2)]X (2a-2h, at 230 K), (ii) reductive elimination of 2a-2h to yield cis-[Pt(CH(2)Ar)(CD(3)CN)(PEt(3))(2)]X (3a-3h) and toluene derivatives (in the range 230-255 K), and finally (iii) spontaneous isomerization of the cis cationic solvento species to the corresponding trans isomers (4a-4h, in the range 260-280 K). All compounds were detected and fully characterized through their (1)H and (31)P{(1)H} NMR spectra. Kinetics monitored by (1)H and (31)P{(1)H} NMR and isotopic scrambling experiments on cis-[Pt(CH(2)Ar)(2)(H)(CD(3)CN)(PEt(3))(2)]X gave some insight onto the mechanism of reductive elimination of 2a-2h. Systematic kinetics of isomerization of 3a-3h were followed in the temperature range 285-320 K by stopped-flow techniques. The process goes, as expected, through the relatively slow dissociative loss of the weakly bonded solvent molecule and interconversion of two geometrically distinct T-shaped three-coordinate intermediates. The dissociation energy depends upon the solvent-coordinating ability. DFT optimization reveals that along the energy profile the "cis-like" [Pt(CH(2)Ar)(PMe(3))(2)](+) intermediate is strongly stabilized by a Pt···η(2)-C1-C(ipso) bond between the unsaturated metal and benzyl carbons. The value of the ensuing stabilization energy was estimated by computational data to be greater than that found for similar β-agostic Pt···η(2)-CH interactions with alkyl groups containing β-hydrogens. An observed consequence of the strong stabilization of "cis"-[Pt(η(2)-CH(2)Ar)(PMe(3))(2)](+) is the remarkable acceleration of the rate of isomerization, greater than that produced by the so-called "β-hydrogen kinetic effect". Kinetic and DFT data concur to indicate that electron donation by substituents on the benzyl ring leads to further stabilization of the "cis"-[Pt(η(2)-CH(2)Ar)(PMe(3))(2)](+) cationic species.

The first six-membered gold(III) N^C^N pincer complex was obtained in good yield, under very mild conditions, by transmetalation of [Hg(κC-N^C^N)Cl] (N^CH^N = 1,3-bis(pyridin-2-ylmethyl)benzene, HL(1)) with Na[AuCl(4)]. The X-ray crystal structure of [Au(N^C^N)Cl][PF(6)] showed that the fused six-membered metallacycles each exist in a strongly puckered boat conformation. As shown by the (1)H NMR spectra in various solvents, the same structure is also retained in solution: no inversion of the six-membered metallacycles is observed in DMSO up to 95 °C. This correlates well with a reaction barrier of 17.5 kcal/mole, as determined by quantum chemical calculations. The reactivity of the present pincer complex is compared to that of the analogous 1,3-bis(2-pyridyl)benzene, HL(2), derivative, which has five-membered fused metallacycles. Sharp differences are found in the reactions with phosphines, such as PPh(3) and dppe (1,2-bis-diphenylphosphino-ethane), and with silver salts. Theoretical calculations were carried out on the two pincer complexes in order to try to understand these differences, and we found that the gold-chlorine bond is significantly stronger in the case of the complex containing five-membered metallacyclic rings.

The hexanuclear cluster {Pt(6)}H(2) (2) contains a sterically hindered and chemically stable {Pt(6)} = Pt(6)(mu-PtBu(2))(4)(CO)(4) core, with the six metals forming an edge-bridged tetrahedron. The two hydrides are the reactive sites of the cluster and lie on opposite sides of the cluster, terminally bonded to the two "apical" edge-bridging platinum centres. Indeed, cluster 2 reacts with acids of different acidity (HA = CF(3)SO(3)H, HBF(4), p-CH(3)-C(6)H(4)-SO(3)H, CF(3)COOH, PhCOOH and CH(3)COOH), affording, after evolution of two equivalents of dihydrogen, the corresponding anion-substituted clusters {Pt(6)}A(2) (4). We suggest that the reaction proceeds through a mechanism similar to the one generally accepted for the analogous protonation of mononuclear hydrides, with some of the intermediates partially characterised at low temperature. Interestingly, the reverse reaction, the heterolytic splitting of H(2) by clusters 4, occurs readily under mild conditions. The anions in clusters 4a and 4b (4a: A = CF(3)SO(3), 4b: A = BF(4)) are bonded in the solid state but very easily dissociate in solution and may be substituted under mild conditions by weak ligands, such as CH(2)Cl(2) or CH(3)CN. With dialkyl ethers, the reaction proceeds further with the heterolytic splitting of a C-H bond of the ethereal ligand. This process allowed us to isolate the polymer [{Pt(6)}(CH(2)OCH(2)CH(2)OCH(2))](x) (8), in which the {Pt(6)} cluster units are connected by insulating spacers arising from dimethoxyethane. The results of single-crystal X-ray diffraction studies on 4a and 8 are also reported.

The CuI catalyzed dehydro-halogenation of 1',1'''-diethynylbiferrocene and {Pt(3)}Cl [{Pt(3)} = Pt(3)(mu-PBu(t)(2))(3)(CO)(2)] (1:2 molar ratio) in diethylamine gives in high yields the bicluster derivative [{Pt(3)}CC-(eta(5)-C(5)H(4))Fe(eta(5)-C(5)H(4))](2), 3, in which two platinum triangles are connected by a diethynylbiferrocene spacer. In the structure of 3, confirmed by a diffractometric study, the two {Pt(3)} fragments lie, perfectly eclipsed, on the same side of the biferrocenyl moiety; this folded structure is also preferred in solution, as suggested by NMR Diffusion Ordered Spectroscopy (DOSY) and 1D Rotating-frame Overhauser Enhancement (ROE) measurements. Compound 3 exhibits a rich redox behavior, with a crowded sequence of six one-electron oxidation processes, the electrode potentials of which have been evaluated by digital simulations. On the basis of a spectroelectrochemical study, the first two oxidations are assigned to the iron centers of the diferrocenyl unit and the subsequent four electrons are removed from the {Pt(3)} units.

Cationic ethylene platinum(II) complexes of the type [Pt(CNN)(C(2)H(4))](+), containing a methyl fragment and different diimines (NN), or terdentate (kappaC-kappa(2)NN') anionic ligands, were synthesized and fully characterized both as solids and in solution [NN = 2,2'-dipyridylamine, 1; 2,2'-dipyridylsulfide, 2; 1,10-phenanthroline, 3; 4,7-diphenyl-1,10-phenanthroline, 4; 3,4,7,8-tetramethyl-1,10-phenanthroline, 5; 2,2'-bipyridine, 6; HC-NN = 6-tert-butyl-2,2'-bipyridine, 7; 6-neo-pentyl-2,2'-bipyridine, 8; 6-phenyl-2,2'-bipyridine, 9; 6-(alpha-methyl)benzyl-2,2'-bipyridine, 10; 6-(alpha-ethyl)benzyl-2,2'-bipyridine, 11; 6-(alpha,alpha-dimethyl)benzyl-2,2'-bipyridine, 12]. Crystals suitable for X-ray analysis of complexes 5 and 7 were obtained. Ethene exchange at the cyclometalated platinum(II) complexes 7, 8, and 10-12 was studied by (1)H NMR line-broadening experiments in chloroform-d, as a function of both temperature and olefin concentrations. For the other prepared complexes the process was too fast to be monitored on the NMR time scale even at the lowest temperature. The ethylene exchange rates show a linear dependence on the concentration of the free ligand, with a negligible k(1) term indicating that either a solvolytic or a dissociative pathway to the products is absent or negligible. The values of the second-order rate constants k(exc), as obtained by linear regression analysis of the experimental data at 298 K, are in a range of ca. 10(4)-10(5) s(-1) m(-1). The activation entropies are negative, ranging between -129 and -112 J K(-1) mol(-1), as expected for associative processes. The activation process is largely entropy controlled: the TDeltaS()() contribution to the free energy of activation is extremely large, amounting to more than 80% for all complexes, with a smaller enthalpy contribution. All the experimental findings evidence that the mechanism takes place via an associative attack by the entering olefin, through a well-ordered, stable pentacoordinated transition state with the two ethene molecules on the trigonal plane. The reactivity of [Pt(CNN)(C(2)H(4))](+) complexes is strongly dependent on the choice of coordinated 6-substituted-2,2'-bipyridines, especially when the terdentate anionic fragment is capable of generating steric crowding and congestion on the coordination plane.

The reaction between Pt(3)(mu-PBu(t)(2))(3)(CO)(2)Cl (2) and ethynylferrocene, in the presence of catalytic amounts of CuI, gives Pt(3)(mu-PBu(t)(2))(3)(CO)(2)C[triple bond]CFc (1), characterized by X-ray crystallography and representing a rare example of the sigma-coordination of an alkynyl moiety to a cluster unit. In a dichloromethane (CH(2)Cl(2)) solution, compound 1 undergoes three consecutive one-electron oxidations, the first of which is assigned to the ferrocene-centered Fe(II)/Fe(III) redox couple. Spectroelectrochemistry, carried out on a solution of 1, shows the presence of a broad band in the near-IR region, growing after the electrochemical oxidation, preliminarily associated with a metal-to-metal charge transfer toward the Fe(III) ion of the ferrocenium unit. Density functional theory (DFT) has been employed to analyze the ground- and excited-state properties of 1 and 1(+), both in the gas phase and in a CH(2)Cl(2) solution. Vertical excitation energies have been computed by the B3LYP hybrid functional in the framework of the time-dependent DFT approach, and the polarizable continuum model has been used to assess the solvent effect. Our results show that taking into account the medium effects together with the choice of an appropriate molecular model is crucial to correctly reproducing the excitation spectra of such compounds. Indeed, the nature of the substituents on P atoms has been revealed to have a key role in the quality of the calculated spectra.

Pulsed gradient spin-echo (PGSE) diffusion characteristics for a) the new [brucinium][X] salts 6 a-f [a: X = BF(4)(-); b: X = PF(6)(-); c: X = MeSO(3)(-), d: X = CF(3)SO(3)(-); e: X = BArF(-); f: X = PtCl(3)(C(2)H(4))(-)], b) 4-tert-butyl-N-benzyl analogue, 7 and c) the aryl carbocations (p-R-C(6)H(4))(2)CH 9 a (R = CH(3)O) and 9 b (R = (CH(3))(2)N), (p-CH(3)O-C(6)H(4))(x)CPh(3-x)(+) 10 a-c (x = 1-3, respectively) and (p-R-C(6)H(4))(3)C(+) 11 (R = (CH(3))(2)N) and 12 (R = H) all in several different solvents, are reported. The solvent dependence suggests strong ion pairing in CDCl(3), intermediate ion pairing in CD(2)Cl(2) and little ion pairing in [D(6)]acetone. (1)H, (19)F HOESY NMR spectra (HOESY: heteronuclear Overhauser effect spectroscopy) for 6 and 7 reveal a specific approach of the anion with respect to the brucinium cation plus subtle changes, which are related to the anion itself. Further, for carbocations 9-12, (all as BF(4)(-) salts) based on the NOE results, one finds marked changes in the relative positions of the BF(4)(-) anion. In these aryl cationic species the anion can be located either a) very close to the carbonium ion carbon b) in an intermediate position or c) proximate to the N or O atom of the p-substituent and remote from the formally positive C atom. This represents the first example of such a positional dependence of an anion on the structure of the carbocation. DFT calculations support the experimental HOESY results. The solid-state structures for 6 c and the novel Zeise's salt derivative, [brucinium][PtCl(3)(C(2)H(4))], 6 f, are reported. Analysis of (195)Pt NMR and other NMR measurements suggest that the eta(2)-C(2)H(4) bonding to the platinum centre in 6 f is very similar to that found in K[PtCl(3)(C(2)H(4))]. Field dependent T(1) measurements on [brucinium][PtCl(3)(C(2)H(4))] and K[PtCl(3)(C(2)H(4))], are reported and suggested to be useful in recognizing aggregation effects.

Our aim was to present a comprehensive, updated survey on obsessive-compulsive disorder (OCD) and obsessive-compulsive related disorders (OCRDs) and their clinical management via literature review, critical analysis and synthesis. Information on OCD and OCRD current nosography, clinical phenomenology and etiology, may lead to a better comprehension of their management. Clinicians should become familiar with the broad spectrum of OCD disorders, since it is a pivotal issue in current clinical psychiatry.

A simple and efficient method for the synthesis of potentially antitumor-active dinuclear platinum complexes of the general formula [{trans-PtCl(NH3)2}2(mu-L)]((n+2)+) (L = aliphatic or heterocyclic diamine; n = charge of L) is presented. The procedure is based on the mutual in situ activation of trans-[PtCl(OH)(NH3)2] and the linker L in the form of a diammonium salt. This synthetic pathway yielded the Farrell compound [{trans-PtCl(NH3)2}2{mu-NH2(CH2)6NH2}]Cl2 (BBR3005) in quantitative yield. Using the same procedure, we prepared the new pyrazolate-bridged compound [{trans-PtCl(NH3)2}2(mu-pz)]Cl, determined its X-ray structure, and tested its cytotoxicity against three wild-type and one cisplatin-resistant cell lines.

PGSE diffusion, 19F, 1H HOESY and 13C NMR studies for a series of [Ru(Cp*)(eta6-arene)][PF6] (1) salts are presented. The solid-state structure of [Ru(Cp*)(eta6-fluorobenzene)][PF6] (1 c) is reported. The extent of the ion pairing and the relative positions of the ions are shown to depend on the arene. For the solvent dichloromethane, new and literature PGSE data for PF6(-) salts of transition-metal, inorganic, and organic salts are compared. Taken together, these new results show that the charge distribution and the ability of the anion to approach the positively charged positions (steric effects due to molecular shape) are the determining factors in deciding the amount of ion pairing. DFT calculations of the charges in four salts of type 1, as well as in a variety of other salts, using a natural population analysis (NPA), support this view. This represents the first attempt, using experimental data, to understand, correlate, and partially explain the various degrees of ion pairing in a widely different collection of salts.

Oscillation of the 2,9-dimethyl-1,10-phenanthroline (dmphen) ligand between nonequivalent exchanging sites in [Pt(Me)(dmphen)(P(o-tolyl)3)]+ and phosphane rotation around the Pt-P bond take place at the same rate. Thus, this cationic complex behaves as a molecular gear, exhibiting a fascinating synchronism between two otherwise independent fluxional motions. The process (DeltaG(3330)(#) = 68.5 +/- 0.2 kJ mol(-1)) was found to be unaffected by (i) the nature of various counteranions (X = PF6- 1, SbF6- 2, CF3SO3- 3, BF4- 4, BArf- 5), (ii) the polarity or the electron-donor properties of the solvent and, (iii) the addition of weak nucleophiles. Restricted phosphane rotation around the Pt-P bond impedes free dmphen oscillation in a 14-electron three-coordinate T-shaped intermediate, containing eta1-coordinated dmphen, generated by easy Pt-N bond dissociation from [Pt(Me)(dmphen)(P(o-tolyl)3)]+. 1-5 undergo easy orthoplatination, leading to new [Pt(dmphen){CH2C6H4P(o-tolyl)2-kappaC,P}]X cyclometalated Pt(II) compounds (X = PF6- 1, SbF6- 2, CF3SO3- 3, BF4- 4, BArf- 5). The kinetics of the cyclometalation of 3 and 4 were followed in tetrachloroethane by both 1H NMR and spectrophotometric techniques (kobs = 1.7 x 10-4 s(-1) at 333 K, DeltaH = 59.3 +/- 3 kJ mol(-1), and DeltaS = -141 +/- 8 J K(-1) mol(-1)). Ring opening of dmphen is again a prerequisite for C-H bond activation, which takes place through a multistep oxidative-addition reductive-elimination pathway. The molecular structure of cyclometalated 10 shows a butterfly shape with two o-tolyl rings projected above and below the coordination plane. Variable-temperature 1H NMR spectra revealed hindered rotation around the P-Cipso(o-tolyl) bonds at rather mild temperatures (DeltaG(3330)(#) = 55.2 +/- 0.4 kJ mol(-1)). Dmphen oscillation results very slowly and is dependent on the nature of the counteranions, of the solvents, and is strongly accelerated by the presence of weak nucleophiles that act as catalysts, according to an associative mode of activation.

A combined kinetic and DFT study of the uncatalyzed isomerization of cationic solvent complexes of the type cis-[Pt(R')(S)(PR3)2]+ (R' = linear and branched alkyls or aryls and S = solvents) to their trans isomers has shown that the reaction goes through the rate-determining dissociative loss of the weakly bonded molecule of the solvent and the interconversion of two geometrically distinct T-shaped 14-electron three-coordinate intermediates. The Pt-S dissociation energy is strongly dependent on the coordinating properties of S and independent of the nature of R'. The energy barrier for the fluxional motion of [Pt(R')(PR3)2]+ is comparatively much lower ( approximately 8-21 kJ mol-1). The presence of beta-hydrogens on the alkyl chain (R' = Et, Prn, and Bun) produces a great acceleration of the reaction rate. This accelerating effect has been defined as the beta-hydrogen kinetic effect, and it is a consequence of the stabilization of the transition state and of the cis-like three-coordinate [Pt(R')(PR3)2]+ intermediate through an incipient agostic interaction. The DFT optimization of [Pt(R')(PMe3)2]+ (R' = Et, Prn, and Bun) reproduces a classical dihapto Pt....eta2-HC agostic mode between the unsaturated metal and a dangling C-H bond. The value of the agostic stabilization energy (in the range of approximately 21-33 kJ mol-1) was estimated by both kinetic and computational data and resulted in being independent of the length of the hydrocarbon chain of the organic moiety. A better understanding of such interactions in elusive reaction intermediates is of primary importance in the control of reaction pathways, especially for alkane activation by metal complexes.

The tridentate dianionic ligand 2-[2'-(hydroxyisopropoxyphosphoryl)phenylsulfanyl]benzoate (L(2-)) reacts with cis-[Pt(NH(3))(2)(H(2)O)(2)](2+) to form an S,O-chelate in which the O-coordinated group is either carboxylate or phosphonate, depending on the degree of protonation of the complex. Carboxylate appears to be the stronger ligand, and the stoichiometric reaction between cis-[Pt(NH(3))(2)(H(2)O)(2)](2+) and L(2-) yields the neutral species [Pt(L)(NH(3))(2)], with L bound by sulfanyl and carboxylate groups, both in solution and in the solid state. Upon protonation of [Pt(L)(NH(3))(2)], the stronger basicity of the carboxylate causes the Pt coordination to switch from carboxylate to phosphonate, and the uncoordinated carboxylate group becomes protonated. In methanolic solution, the first-order kinetics of this rearrangement could be observed by (31)P NMR spectroscopy. Both complexes-the carboxylate-bound neutral complex [Pt(L)(NH(3))(2)].H(2)O (triclinic, P1 (no. 2), a=9.529(6), b=9.766(6), c=12.299(7) angstroms, alpha=106.91(2), beta=101.71(2), gamma=102.05(2) degrees, Z=2) and the perchlorate salt of the phosphonate-bound complex [Pt(LH)(NH(3))(2)]ClO(4).H(2)O (monoclinic, P2(1)/c (no. 14), a=12.095(2), b=14.046(2), c=14.448(2) angstroms, beta=95.55(2) degrees, Z=4)-were characterized by X-ray crystallography.

This study was designed to evaluate the activity and tolerability of irinotecan and docetaxel in patients with previously treated non-small cell lung cancer (NSCLC). Eligibility included recurrent or progressive NSCLC, previous chemotherapy, age > or = 18 years, ECOG PS < or = 2. Treatment consisted of irinotecan (160 mg/m2 i.v.), followed by docetaxel (65 mg/m2 i.v.) on day 1 of a 21-day cycle, for a maximum of 6 cycles. Forty patients were enrolled. Median age was 60 years and median ECOG PS was 1. All patients were evaluable for toxicity and 31 (78%) were evaluable for response. A total of 125 cycles was administered (median, 3; range, 1-6). Most common grade 3-4 toxicities were neutropenia (62%), neutropenic fever (22%), and diarrhea (32%). Response rate was 10%; a further 40% of patients achieved stable disease. All responses were observed in patients with ECOG PS < or = 1, age <70 years, and who had received only one prior chemotherapy regimen. Median time to progression was 2.8 months and median survival was 7.4 months. Because of significant toxicity and limited activity, further investigation of irinotecan plus docetaxel in second line NSCLC is not recommended.

Treatment of Ru(eta4-C8H12)(eta6-C8H10) with 3 bar H2 in the presence of 2 equiv of tricyclopentylphosphine (PCyp3) in pentane resulted in the isolation of the new bis(dihydrogen) complex RuH2(eta2-H2)2(PCyp3)2 (2), characterized by NMR and single-crystal X-ray and neutron diffraction. The single-crystal neutron diffraction study is the first carried out for a bis(dihydrogen) complex. The coordination geometry around the metal center is a distorted octahedron defined by the two phosphines in a trans configuration (making an angle of 168.9(1) degrees ), two cis dihydrogen ligands, and two hydrides trans to them, defining the equatorial plane. The H-H bond distances (0.825(8) and 0.835(8) A) are characteristic of two "unstretched" dihydrogen ligands. H/D exchange between the Ru-H and the C-D bonds of deuterated benzene is observed within 1 h, leading to the formation of various isotopomers RuHxD6-x(PCyp3)2 (with x = 0-6). 2 is a catalyst precursor for ethylene coupling (20 bar, 293 K) to a functionalized arene (Murai reaction). We found a 90% conversion of acetophenone to 2-ethylacetophenone within 35 min, whereas 10 h was needed in the same conditions using the analogous tricyclohexylphosphine complex, RuH2(eta2-H2)2(PCy3)2, the best catalyst precursor, at room temperature, prior to this work.

A dynamic 1H NMR study has been carried out on the fluxional motion of the symmetric chelating ligand 2,9-dimethyl-1,10-phenanthroline (Me2-phen) between nonequivalent exchanging sites in a variety of square-planar complexes of the type [Pt(Me)(Me2-phen)(PR3)]BArf, 1-14, (BArf = B[3,5-(CF3)2C6H3]4). In these compounds, the P-donor ligands PR3 encompass a wide range of steric and electronic characteristics [PR3 = P(4-XC6H4)3, X = H 1, F, 2, Cl 3, CF3 4, MeO 5, Me 6; PR3 = PMe(C6H5)2 7, PMe2(C6H5) 8, PMe3 9, PEt3 10, P(i-Pr)3 11, PCy(C6H5)2 12, PCy2(C6H5) 13, PCy3 14]. All complexes have been synthesized and fully characterized through elemental analysis, 1H and 31P{1H} NMR. X-ray crystal structures are reported for the compounds 8, 11, 14, and for [Pt(Me)(phen)(P(C6H5)3)]PF6 (15), all but the last showing loss of planarity and a significant rotation of the Me2-phen moiety around the N1-N2 vector. Steric congestion brought about by the P-donor ligands is responsible for tetrahedral distortion of the coordination plane and significant lengthening of the Pt-N2 (cis to phosphane) bond distances. Application of standard quantitative analysis of ligand effects (QALE) methodology enabled a quantitative separation of steric and electronic contributions of P-donor ligands to the values of the platinum-phosphorus 1J(PtP) coupling constants and of the free activation energies DeltaG++ of the fluxional motion of Me2-phen in 1-14. The steric profiles for both 1J(PtP) and DeltaG++ show the onset of steric thresholds (at cone angle values of 150 degrees and 148 degrees , respectively), that are associated with an overload of steric congestion already evidenced by the crystal structures of 11 and 14. The sharp increase of the fluxional rate of Me2-phen can be assumed as a perceptive kinetic tool for revealing ground-state destabilization produced by the P-donor ligands. The mechanism involves initial breaking of a metal-nitrogen bond, fast interconversion between two 14-electron three-coordinate T-shaped intermediates containing eta1-coordinated Me2-phen, and final ring closure. By use of the results from QALE regression analysis, a free-energy surface has been constructed that represents the way in which any single P-donor ligand can affect the energy of the transition state in the absence of aryl or pi-acidity effects.

The crystal structures of six nitrotoluene derivatives, synthesized by Wilhelm Koerner about a century ago and retrieved from a depository at the University of Milano, were determined. The correct assignment of molecular structures is verified. The geometry of the nitro groups and factors affecting the orientation of nitro groups with respect to the benzene ring are discussed, also using an auxiliary set of crystal structures retrieved from the Cambridge Structural Database. The crystal packings have been analyzed, and lattice energies have been calculated by atom-atom potential methods and by the newly proposed Pixel method. This method allows a more complete description of intermolecular potentials in terms of the interaction between molecular electron densities and separate Coulombic, polarization, dispersion and overlap repulsion energies. Lattice vibrations and external entropies were calculated by lattice-dynamical procedures. The results of the Pixel energy calculations allow a reliable, quantitative assessment of the relative importance of stacking interactions and hydrogen bonding in the rationalization of the recognition modes of nitrobenzene derivatives, which is impossible to attain using only qualitative atom- atom geometry concepts.

Aim of this study was to determine the activity and toxicity of a sequential chemotherapy regimen in advanced non-small cell lung cancer (NSCLC). Fifty-one previously untreated stage IIIB/IV NSCLC patients were enrolled to receive two cycles of cisplatin plus paclitaxel (80/175 mg/m(2) every 21 days), followed by two cycles of vinorelbine (30 mg/m(2) on days 1 and 8 every 21 days), followed by two cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days). Forty-one patients (82%) completed the planned six cycles. Grade 3-4 neutropenia was the major toxicity (41% of patients) and it was mainly associated with vinorelbine administration. Response rate after cisplatin plus paclitaxel was 18%; this percentage increased to 41% after vinorelbine, and it reached 43% upon completion of the entire six cycle treatment program. Median survival time was 14.4 months, 1-year survival rate was 53%, and 2-year survival rate was 18%. Median time to disease progression was 6.8 months. This sequential chemotherapy regimen is feasible and active in patients with advanced NSCLC. This pilot experience provides the basis for an ongoing randomized phase III trial comparing our sequential regimen versus cisplatin plus gemcitabine.

The self-assembly of 1,12-dodecanedinitrile (ddn) with various silver salts (NO(3)(-), PF(6)(-), AsF(6)(-), ClO(4)(-)) afforded new polymeric coordination networks with the general formula [Ag(ddn)(2)]X. All these species contain interpenetrating diamondoid nets showing interesting features: with X=NO(3)(-) the cationic [Ag(ddn)(2)](+) network exhibits the highest interpenetration (tenfold) ever found within diamondoid nets exclusively based on coordinative bonds. When X=PF(6)(-) or AsF(6)(-) an eightfold diamondoid network is obtained that shows an unusual [4+4] mode of interpenetration, instead of the "normal" set of eight nets equally translated along a principal axis of the adamantanoid cages. The polymeric species that forms with X=ClO(4)(-) is a fourfold interpenetrating diamondoid network; the lower degree of interpenetration in this case is related to the conformation assumed by the flexible ddn ligands.