Biochemical and Neuropathological Findings in a Creutzfeldt-Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene.

Genetic Creutzfeldt-Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

Single-stage Orbital Decompression, Strabismus and Eyelid Surgery in Moderate to Severe Thyroid Associated Orbitopathy.

PURPOSE: To evaluate the outcome of orbital decompression, strabismus and/or eyelid surgery in patients with moderate to severe thyroid-associated orbitopathy, when combined approach is preferred. METHODS: Retrospective, comparative, non-randomized review of 45 patients operated on from 2015 to 2018. Simultaneous decompression, eyelid and/or strabismus surgery was performed in 34 eyes of 20 subjects (group 1). Patients with multi-step procedures were used as control groups: group 2 included patients with staged decompression and eyelid retraction surgery (15 cases, 19 eyes); group 3 included patients with staged decompression and vertical strabismus surgery (10 cases, 13 eyes). Mean follow-up was 2.9 ± 1.8 years. Mann Whitney two-tailed test was used for paired data, and Fisher's exact test for categorical data; p <.05 were considered statistically significant. RESULTS: Changes in margin reflex distance were not significantly different among patients of subgroup 1A (11 patients, one-step decompression/eyelid surgery) and group 2 (p >.05). Improvement in postoperative diplopia were not significantly different among patients of subgroup 1B (9 cases, one-step decompression/strabismus/eyelid surgery) and group 3 (p >.05). One patient of group 1 had recurrent dysthyroid optic neuropathy that recovered with steroid treatment. No other complications occurred in the one-step surgery group. CONCLUSIONS: Simultaneous orbital decompression, strabismus and/or eyelid surgery resolved dysthyroid optic neuropathy, decreased proptosis, improved diplopia and eyelid position with a range comparable to that of a multi-step technique. If confirmed in prospective controlled studies, a one-stage approach might be advised to reduce the costs and time needed for rehabilitation in selected patients.

Nasal histamine responses in nonallergic rhinitis with eosinophilic syndrome.

BACKGROUND: Nonallergic rhinitis with eosinophilic syndrome (NARES) is persistent, without atopy, but with ≥25% nasal eosinophilia. Hypereosinophilia seems to contribute to nasal mucosa dysfunction. OBJECTIVES: This analytical case-control study aimed at assessing the presence and severity of nonspecific nasal hyperactivity and at finding out whether eosinophilia may be correlated with the respiratory and mucociliary clearance functions. MATERIALS: The symptom score was assessed in 38 patients and 15 controls whose nasal smear was also tested for eosinophils and mucociliary transport (MCT). Nonspecific nasal provocation tests (NSNPT) with histamine were also carried out, and total nasal resistance (TNR) was determined. RESULTS: The symptom score of NARES after NSNPT were not significantly different from the control group, and there was poor or no correlation among the single symptoms and the differences studied for every nasal reactivity class. This correlation improved when using the composite symptom score. The most severe eosinophilia was observed in high reactivity groups, and it was correlated with an increase in TNR. MCT worsened as eosinophilia and nasal reactivity increased. Unlike controls, a significant correlation was observed between the increase in MCT and TNR. CONCLUSIONS: In NARES, nonspecific nasal hyperreactivity is the result of epithelial damage produced by eosinophilic inflammation, which causes MCT slow down, an increase in TNR, and nasal reactivity classes, with possible impact on classification, prognosis, and treatment control.

Mechanistic insight into protonolysis and cis-trans isomerization of benzylplatinum(II) complexes assisted by weak ligand-to-metal interactions. A combined kinetic and DFT study.

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···Î·(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 ß-agostic Pt···Î·(2)-CH interactions with alkyl groups containing ß-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 "ß-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.

Synchronized fluxional motion and cyclometalation of ligands in platinum(II) complexes.

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.

beta-Hydrogen Kinetic Effect.

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.

Platinum(II) complexes bearing 1,1'-bis(diphenylphosphino)ferrocene as building blocks for functionalized redox active porphyrins.

Reactions of the cationic complex ions [PtMe(Me2SO)(PP)]+ (PP = dppf (1,1'-bis(diphenylphosphino)ferrocene) and dppe (1,2-bis(diphenylphosphino)ethane)) with 5,10,15,20-tetrakis(4-pyridyl)-21H,23H-porphyrin (TpyP) led to the formation of the symmetrical tetraplatinated porphyrin complexes, [PtMe(PP)]4TpyP.X4 (PP = dppf, X = CF3SO3-, 3, and PP = dppe, X = BF4-, 5) containing the organometallic fragment [PtMe(PP)]. The precursor sulfoxide platinum complexes [PtMe(Me2SO)(dppf)]CF3SO3, 2 and [PtMe(Me2SO)(dppe)]BF4, 4, were prepared by halide abstraction from [PtMeCl(dppf)], 1, and by controlled protonolysis of [PtMe2(dppe)] respectively, in the presence of a small amount of dimethyl sulfoxide. All these starting platinum(II) compounds, as well as the porphyrin derivatives 3 and 5, were fully characterized through elemental analysis, 1H NMR mono- and bidimensional, 31P[1H], 31P-1H HMBC, UV/Vis absorption and photophysical measurements. The X-ray crystal structure of complex 1 has been determined. In order to ascertain the electronic influence of ferrocene, the spectroscopic and redox properties of 3 were compared with those of TPyP and of the analogous 5. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), 1H and 31P NMR data, and UV/Vis data, all suggest a certain degree of communication between the central porphyrin and the peripheral hetero-bimetallic fragments. In contrast, no detectable interaction among these peripheral groups seem to come into play. Unlikely from the porphyrin derivative 5, formation of well defined fluorescent mesoscopic ring structures was easily achieved by simple evaporation from diluted dichloromethane solutions of 3.

Epidemiological aspects of olfactory dysfunction.

PURPOSE: This study aimed at assessing the most common aetiological factors causing total or partial olfactory deficit and the statistical analysis of some clinical aspects. MATERIALS AND METHODS: 243 patients reporting alfactory dysfunction were enrolled in this STUDY: A case history was drawn up for each patient, and all of them underwent otolaryngology objective examination, including nasal endoscopy, paranasal sinuses CT-scan, and Utrecht method (GITU) based smell indentification test. RESULTS: Upper respiratory viral infections (40.2%), ceanial-facial traumas (39.3%), and rhinosinusal pathologies (6.3%) were the main aetiopathological factors indentified. A relevant number of case were recorded with unknown aetiology (14.2%). In 2 cases, olfactory dysfunction was due to neurological diseases, in 1 case it was due to intoxication and, in another case, it was congenital. The correlation between aetiology, gender, age, symptoms duration and deficit severity was studied. CONCLUSIONS: many different aetiological factors caused the loss or weakening of the sense of smell. They mainly affected olfactory neurosensorial structures and odorant conduction. However, there were many cases of unknown aetiology. Women, over 40 in particular, were the most affected. Anosmia and severe hyposmia were mainly correlated with traumas and viral pathologies.

Structural properties and dissociative fluxional motion of 2,9-dimethyl-1,10-phenanthroline in platinum(II) complexes.

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.

Atropisomerization, C-H activation, and dissociative substitution at some biphenyl platinum(II) complexes.

The reaction of 2,2'-dilithiumbiphenyl with cis-[PtCl(2)(SEt(2))(2)] at -10 degrees C in diethyl ether not only leads to the main product [Pt(2)(micro-SEt(2))(2)(bph)(2)], containing the planar 2,2'-biphenyl dianion (bph(2)(-)), but also forms a new dinuclear platinum(II) compound of formula [Pt(2)(micro-SEt(2))(2)(Hbph)(4)], 1a (Hbph(-) = eta(1)-biphenyl monoanion), in which each metal is in a square-planar environment. NMR spectroscopy and molecular mechanics (MMFF) calculations were used to characterize 1a. The results suggest that the favored conformation for the four Hbph biphenyl groups is alphabetabetaalpha. In chloroform solution, 1a undergoes atropisomerization to 1b (alphabetaalphabeta) (k(is) = 1.03 x 10(-)(4) s(-)(1), at 298 K) that subsequently cyclometalates (k(obs) = 4.48 x 10(-)(6) s(-)(1), at 298 K) to yield [Pt(2)(micro-SEt(2))(2)(bph)(2)] and biphenyl. Both processes, atropisomerization and C-H activation, presumably involve preliminary thioether bridge splitting. The dinuclear complex 1a has been shown to be a versatile and useful precursor to a variety of mononuclear eta(1)-biphenyl platinum(II) complexes. By reaction with diethyl sulfide, dimethyl sulfoxide, or with rigid dinitrogen containing ligands, such as 2,2'-bipyridine or 1,10-phenanthroline, complexes cis-[Pt(Hbph)(2)(dmso)(2)] 3, cis-[Pt(Hbph)(2)(SEt(2))(2)] 4, [Pt(Hbph)(2)(bpy)] 5, and [Pt(Hbph)(2)(phen)] 6 were obtained, respectively. The crystal structures of compounds 5 and 6 were determined. Only the head-to-tail isomer of these compounds was recognized in the solid state and in solution, where restricted rotation around the Pt-C bond prevents interconversion to the head-to-head form. A detailed kinetic study of ligand (dmso) exchange and substitution (by 2,2'-bipyridine and 1,10-phenanthroline) has been performed on complex 3 in CDCl(3) and toluene-d(8) by (1)H NMR magnetization transfer experiments, and in toluene by UV/vis spectroscopy, respectively. The rates of both processes show no dependence on ligand concentration, the rate of ligand substitution being in reasonable agreement with that of ligand exchange at the same temperature. The kinetics are characterized by largely positive entropies of activation. The results are consistent with a dissociative mode of activation analogous to the pattern already found for compounds with a similar [Pt(C,C)(S,S)] set of coordinating ligands. The role of ML(3) d(8) T-shaped 14-electron species, as elusive reaction intermediates or structurally characterized compounds, is discussed.

Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium.

Modifications of natural DNA by the dinuclear platinum(II) organometallic complex [[Pt(Me)Cl(Me(2)SO)](2)(mu-N-N)] [where N-N=H(2)N(CH(2))(6)NH(2)] (ORGANObisPt) were studied by methods of molecular biophysics. These methods include DNA binding studies using atomic absorption spectrophotometry, HPLC analysis of enzymatically digested DNA, interstrand cross-linking employing gel electrophoresis under denaturing conditions, DNA unwinding studied by gel electrophoresis, mapping of DNA adducts by transcription assay, DNA melting curves measured by absorption spectrophotometry and conformational analysis of platinated DNA by differential pulse polarography. The results indicate that the complex ORGANObisPt binds irreversibly to DNA. Its DNA binding mode is, however, different from that of the formally equivalent [[cis-PtCl(NH(3))(2)](2)(mu-N-N)] (1,1/c,c), which exhibits antitumor activity including that in the tumor cells resistant to cisplatin. Interestingly, ORGANObisPt binds to DNA considerably faster than 1,1/c,c and cisplatin. In addition, when ORGANObisPt binds to DNA it exhibits a strong base sequence specificity to guanine residues. ORGANObisPt forms mainly monofunctional adducts on double-helical DNA. It forms also a small amount of DNA interstrand cross-links (approximately 2%), i.e. a radically smaller amount in comparison with the complex 1,1/c,c. Importantly, these interstrand cross-links of ORGANObisPt are capable of terminating RNA synthesis in vitro, while its major monofunctional adducts are not. In addition, the adducts of ORGANObisPt affect the conformation of DNA, but in a different way than its dinuclear analogue 1,1/c,c or cisplatin. Some structural features of ORGANObisPt, such as the charge or nature of the trans and cis activating groups relative to the labile chloride, might be responsible for the altered DNA binding mode and biological activity in comparison with the 1,1/c,c compound.

Synthetic procedures to monomethyl-platinum(II) complexes containing nitrogen ligands of biological relevance.

The complex trans-bis(dimethylsulfoxide)chloromethylplatinum(II) (1) is fairly soluble in water, where it undergoes multiple equilibria involving the formation of geometrically distinct [Pt(H(2)O)(DMSO)Cl(CH(3))] aqua-species. On reacting an aqueous solution of 1 with monodentate nitrogen donor ligands L, such as pyridines or amines, two well distinct patterns of behavior can be recognized: (i) a single stage fast substitution of one DMSO by the entering ligand, yielding a complex of the type trans(C,N)-[Pt(DMSO)(L)Cl(CH(3))] which contains four different groups coordinated to the metal and which undergoes a slow conversion into its cis-isomer, (ii) a double substitution affording cationic complex ions of the type cis-[Pt(L)(2)(DMSO)(CH(3))](+). When this latter reaction is carried out using sterically hindered ligands, slow rotation of the bulk ligand around the Pt[bond]N bond allows for the identification of head-to-head and head-to-tail rotamers in solution, through (1)H NMR spectrometry. The addition of chloride anion to 1 leads to the anionic species cis-[Pt(DMSO)Cl(2)(CH(3))](-), where a molecule of DMSO still remains coordinated to the metal center, despite its quite fast rate of ligand exchange (k(exch) with free DMSO=12+/-1 s(-1)). The reaction of complex 1 with bidentate ligands, such as ethylenediamine (en) or simple amino acids, leads to the cationic species [Pt(en)(DMSO)(CH(3))](+) or to the neutral [Pt(DMSO)(N[bond]O)(CH(3))], (where N[bond]-O[double bond]GlyO(-), AlaO(-)).

Catalytic effect of sulfoxides on the fluxional motion of 2,9-dimethyl-1,10-phenanthroline in a platinum(II) complex: evaluation of steric and electronic contributions.

Addition of external weak nucleophiles to a chloroform solution of the cationic complex ion [Pt(Me)(dmphen)(PPh(3))](+) (1) accelerates the fluxional motion of the symmetric chelating ligand 2,9-dimethyl-1,10-phenanthroline (dmphen) between nonequivalent exchanging sites. The rates of the dynamic process can be measured by line-shape analysis of the (1)H NMR spectra. Concentration-dependent measurements were carried out with the ligands SOMe(2), SO(CH(2))(4), SO(n-Bu)(2), SO(sec-Bu)(2), SO(i-Pr)(2), SOEt(Ph), SOPr(Ph), SO(Bz)(2), SO(p-MeC(6)H(4))(2), SOPh(2), SO(p-ClC(6)H(4))(2), SOMe(p-MeOC(6)H(4)), SOMe(p-MeC(6)H(4)), SOMe(Ph), SOMe(p-BrC(6)H(4)), and SOMe(p-ClC(6)H(4)). The rate constants k(obsd), when plotted against the concentration of the added ligands SOR(R'), give a family of straight lines with a common intercept, indicating that the two-term rate law k(obsd) = k(1) + k(2)[SOR(R')] is obeyed. The same rate law applies to the displacement of SOMe(2) from [Pt(Me)(phen)(SOMe(2))](+) (2) (phen = 1,10-phenanthroline) by sulfoxides (SOMe(2), SO(i-Pr)(2), SOMe(p-MeOC(6)H(4)), SO(p-MeC(6)H(4))(2), SOPh(2), SO(p-ClC(6)H(4))(2), and SO(sec-Bu)(2)). The fluxional rates in 1 are 6-7 orders of magnitude higher than the substitution rates in 2. The values of the rate constants for the two processes were resolved quantitatively into steric and electronic contributions by use of quantitative analysis of ligand effects (QALE). Inhibitory steric effects are linearly operative for the entire set of ligands, the rates of the reactions are enhanced with increasing electron donor capacity of the sulfoxides, and there is a small but significant E(ar) effect that enhances the reactivity of the aryl sulfoxides. The strict similarity of the patterns of the two processes and of their dependence upon the stereoelectronic properties of the ligands, combined with the intrinsic lability of the platinum-nitrogen bonds, would suggest the operation of stereospecific consecutive ring-opening and ring-closure steps for the fluxional motion of dmphen in 1. However, the available evidence does not allow alternative mechanisms involving intramolecular rearrangements of the five-coordinate intermediate to be ruled out.

Synthesis, Characterization, Absorption Spectra, and Luminescence Properties of Organometallic Platinum(II) Terpyridine Complexes.

A series of new organometallic platinum(II) complexes containing terdentate polypyridine ligands has been prepared and characterized. Their absorption spectra in 4:1 (v/v) MeOH/EtOH fluid solution at room temperature and luminescence in the same matrix at 77 K have been investigated. The new species are [Pt(terpy)Ph]Cl (3, terpy = 2,2':6',2"-terpyridine, Ph = phenyl), [Pt(Ph-terpy)Cl]Cl (4, Ph-terpy = 4'-phenyl-2,2':6',2"-terpyridine), [Pt(Ph-terpy)Me]Cl (5), and [Pt(Ph-terpy)Ph]Cl (6). The results have been compared with those for [Pt(terpy)Cl]Cl (1) and [Pt(terpy)Me]Cl (2). NMR data evidence that all the complexes but 3 and 6 oligomerize in solution leading to stacked species. The absorption spectra are dominated by moderately intense metal-to-ligand charge-transfer (MLCT) bands in the visible region and by intense ligand-centered (LC) bands in the UV region. All the compounds are luminescent in a 4:1 (v/v) MeOH/EtOH rigid matrix at 77 K, exhibiting a structured emission within the range 460-600 nm. This feature is assigned to formally (3)LC excited states which receive substantial contribution from closely lying (3)MLCT levels. Complexes 1, 2, 4, and 5 also exhibit a relatively narrow and unstructured luminescence band within the range 680-800 nm, which dominates the luminescence spectrum on increasing concentration and exciting at longer wavelengths. The band is assigned to a dsigma(metal) --> pi(polypyridine) ((3)MMLCT) state, originating from metal-metal interactions occurring in head-to-tail dimers (or polymers). A third broad band is shown by 1 and 4 under all concentration conditions and by 2 and 5 only in concentrated solutions and is attributed to excimeric species originating from pi-pi interactions due to stacking between polypyridine ligands.

Molecular Structure, Acidic Properties, and Kinetic Behavior of the Cationic Complex (Methyl)(dimethyl sulfoxide)(bis-2-pyridylamine)platinum(II) Ion.

The complex [PtMe(dpa)(Me(2)SO)](+)(CF(3)SO(3))(-) (dpa = bis(2-pyridyl)amine) crystallizes in the monoclinic space group P2(1)/c with a = 11.010(2) Å, b = 18.366(2) Å, c = 10.333(5) Å, beta = 111.62(2) degrees, and Z = 4. Least-squares refinement of the structure led to an R factor of 2.41%. To avoid steric repulsions, the chelate six-membered ring assumes a boat configuration in which the two pyridyl rings are folded with a dihedral angle of 46.4(1) degrees. There is a strong hydrogen-bonding interaction involving the amine hydrogen (N3) and a triflate anion oxygen O3, 2.898(5) Å. The tendency by the NH group of the ligand moiety to attract anions is maintained in a solution of nonpolar solvents. Tight ion-pairs of structure similar to that in the solid state are formed with PF(6)(-), BF(4)(-), CF(3)SO(3)(-), and Cl(-) in chloroform, as shown by the strong dependence of the chemical shifts of the NH, H(3), and H(3') protons of the dpa ligand on the nature of the counterion. (19)F{(1)H} HOESY experiments on [PtMe(dpa)(Me(2)SO)](+)(PF(6))(-) in CD(2)Cl(2) confirmed that the preferential position of the counterion is close to the NH proton. The absorption spectra are also strongly affected by the nature of the counterion. This allowed for a stopped-flow measure of the PF(6)(-) for Cl(-) exchange rate at the NH site, which is a bimolecular process with k(2) = 96.4 +/- 4 M(-)(1) s(-)(1). The cation [PtMe(dpa)(Me(2)SO)](+) shows acidic properties in water (pK(a) = 12.1 +/- 0.2, at 25 degrees C, &mgr; = 0.1 M, NaNO(3)), and the corresponding amido species [PtMe(dpa-H)(Me(2)SO)] can be isolated on basification. Ion-pairing and full deprotonation of the amine ligand have remarkably little effect on the reactivity, as shown by the comparison of the rates of isotopic exchange of dimethyl sulfoxide of these species followed by (1)H NMR in chloroform. The rates of substitution of dimethyl sulfoxide from [PtMe(dpa)(Me(2)SO)](+) by various charged nucleophiles were measured in methanol, where ion-pairing effects are absent, and compared with those of the parent [PtMe(phen)(Me(2)SO)](+) (phen = 1,10-phenanthroline) complex. Because of the reduced capacity of electron withdrawal from the metal of the ancillary ligand, the dpa complex is less reactive and possesses a minor nucleophilic discrimination ability compared with the phen complex.

Structure-Reactivity Correlations for the Dissociative Uncatalyzed Isomerization of Monoalkylbis(phosphine)platinum(II) Solvento Complexes.

Complexes of the type cis-[PtL(2)Me(2)] (1-14) (L = an extended series of phosphines of widely different steric and electronic properties) were synthesized, characterized, and used as precursors for the formation of cis-monoalkylplatinum(II) solvento species in methanol. The cleavage of the first platinum-alkyl bond by protonolysis is a fast process, but the subsequent cis to trans isomerization of the cationic solvento species [PtL(2)(Me)(MeOH)](+) is relatively slow and it can be( )()monitored using (31)P NMR or conventional spectrophotometry. A large collection of (1)H and (31)P NMR data for cis-[PtL(2)Me(2)], cis-[PtL(2)Me(MeOH)](+), and trans-[PtL(2)Me(MeOH)](+) complexes showed interesting dependencies upon the size, the sigma-donor capacity, and the mutual position of the phosphines in the coordination sphere of the metal. The rate constants for isomerization of cis-[PtL(2)Me(MeOH)](+) were resolved quantitatively into steric and electronic contributions of the phosphine ligands, by means of correlations with parameters which reflect their sigma-donor ability (chi values) and steric requirements (Tolman's cone angles, theta). The electronic and steric profiles obtained for these reactions are discussed within the framework of a mechanism which involves dissociative loss of the solvent molecule and interconversion of two geometrically distinct 3-coordinate T-shaped 14-electron intermediates. The factors controlling the stability of these coordinatively unsaturated species are discussed. The electronic and steric influences of phosphines as "spectator" ligands in a dissociative process are compared with those shown by these ligands when used as nucleophiles in associative substitution processes. The activation parameters DeltaH() and DeltaS() were measured using both conventional isothermal and non-isothermal spectrophotometric kinetics.

Protonolysis of Dialkyl- and Alkylarylplatinum(II) Complexes and Geometrical Isomerization of the Derived Monoorgano-Solvento Complexes: Clear-Cut Examples of Associative and Dissociative Pathways in Platinum(II) Chemistry.

Protonolysis of the complexes cis-[PtR(2)(PEt(3))(2)] (R = Me, Et, Pr(n)(), Bu(n)(), CH(2)C(Me)(3), CH(2)Si(Me)(3)) and cis-[Pt(R)(R')(PEt(3))(2)] (R = Ph, 2-MeC(6)H(4), 2,4,6-Me(3)C(6)H(2); R' = Me) in methanol selectively cleaves one alkyl group, yielding cis-[Pt(R)(PEt(3))(2)(MeOH)](+) and alkanes. The reactions occur as single-stage conversions from the substrate to the product. There is no evidence by UV and by low-temperature (1)H and (31)P NMR spectroscopy for the presence of significant amounts of Pt(II) or Pt(IV) intermediate species. Reactions are first order with respect to complex and proton concentrations and are strongly retarded by steric congestion at the Pt-C bond, varying from k(2) = (2.65 +/- 0.08) x 10(5) M(-)(1) s(-)(1) for R = R' = Et to k(2) = 9.80 +/- 0.44 M(-)(1)s(-)(1) for R = R'= CH(2)Si(Me)(3). Low enthalpies of activation and largely negative volumes of activation are associated with the process. The mechanism involves a rate-determining proton transfer either to the metal-carbon sigma bond (S(E)2 mechanism) or to the metal center (S(E)(oxidative) mechanism), followed by fast extrusion of the alkane and simultaneous blocking of the vacant coordination site by the solvent to generate cis-[Pt(R)(PEt(3))(2)(MeOH)](+) species. The subsequent slower process, cis to trans isomerization of cis-[Pt(R)(PEt(3))(2)(MeOH)](+), is characterized by high values of enthalpies of activation, positive entropies of activation, and largely positive volumes of activation. The reaction is shown to proceed through the dissociative loss of the weakly bonded molecule of solvent and the interconversion of two geometrically distinct T-shaped 14-electron 3-coordinate intermediates. The presence of beta-hydrogens on the residual alkyl chain produces a great acceleration of the rate (R = Me, k(i) = 0.0026 s(-)(1); R = Et, k(i) = 44.9 s(-)(1)) as a consequence of the stabilization of the 3-coordinate [Pt(R)(PEt(3))(2)](+) transition state through an incipient agostic interaction. The results of this work, together with those of a previous paper, give a rationale of the "elusive" nature of these compounds. The following factors concur: (i) electron release by the phosphine ligands, (ii) steric repulsion and distortion of the square-planar configuration, and (iii) interaction of the metal with beta-hydrogens.

Rates of Dimethyl Sulfoxide Exchange in Monoalkyl Cationic Platinum(II) Complexes Containing Nitrogen Bidentate Ligands. A Proton NMR Study.

A series of monoalkyl square-planar complexes of the type [Pt(N-N)(CH(3))(Me(2)SO)]PF(6) (1-14), where N-N represents chelating diamines or diimines of widely different steric and electronic characteristics, was synthesized, and the complexes were fully characterized as solids and in solution. The substrates were tailored to offer only one site of exchange to a neutral molecule, i.e. Me(2)SO, in a noncoordinating solvent. No evidence for fluxionality of the N-N ligands was found, except for the case of complex 11 formed by 2,9-dimethyl-1,10-phenanthroline. In solution this complex is fluxional with the phenanthroline oscillating between nonequivalent bidentate modes by a mechanism which involves rupture of the metal-nitrogen bond and rapid interconversion of two coordinatively unsaturated T-shaped 14-electron three-coordinate molecular fragments. Rates of this fluxion were measured by NMR spectroscopy from the exchange effects on the (1)H signals of the methyl and aromatic hydrogens. The DeltaG() value for the fluxion is 49.6 +/- 4 kJ mol(-)(1). Dimethyl sulfoxide exchange with all the complexes has been studied as a function of ligand concentration by (1)H NMR line-broadening, isotopic labeling, and magnetization transfer experiments with deuterated acetone as the solvent. Second-order rate constants were obtained from linear plots of k(obs) vs [Me(2)SO] and activation parameters were obtained from exchange experiments carried out at different temperatures. Second-order kinetics and negative entropies of activation indicate an associative mechanism. The lability of dimethyl sulfoxide in the complexes depends in a rather unexpected and spectacular way upon the nature of the coordinate N-N ligands, the difference in reactivity between the first (N-N = N,N,N',N'-tetramethyl-1,2-diaminoethane, k(2)(298) = (1.15 +/- 0.1) x 10(-)(6) mol(-)(1) s(-)(1)) and the last (N-N = 2,9-dimethyl-1,10-phenanthroline, k(2)(298) = (3.81 +/- 0.005) x10(4) mol(-)(1) s(-)(1)) members of the series being greater than 10 orders of magnitude, as a result of a well-known phenomenon of steric retardation (for the first complex) and an unprecedented case of steric acceleration (for the last complex). Other factors of primary importance in controlling the reactivity are (i) the presence of an extensive pi system on the ligand N-N, (ii) the ease with which this pi system interacts with nonbonding d electrons of the metal, and (iii) the flexibility and ease of elongation of the chelate bite distance. The basicity plays a somewhat minor role, except in the restricted range of the same class of compounds such as substituted phenanthrolines.