The first solid-state route to luminescent Au(I)-glutathionate and its pH-controlled transformation into ultrasmall oligomeric Au10-12(SG)10-12 nanoclusters for application in cancer radiotheraphy.

There is still a need for synthetic approaches that are much faster, easier to scale up, more robust and efficient for generating gold(I)-thiolates that can be easily converted into gold-thiolate nanoclusters. Mechanochemical methods can offer significantly reduced reaction times, increased yields and straightforward recovery of the product, compared to the solution-based reactions. For the first time, a new simple, rapid and efficient mechanochemical redox method in a ball-mill was developed to produce the highly luminescent, pH-responsive Au(I)-glutathionate, [Au(SG)]n. The efficient productivity of the mechanochemical redox reaction afforded orange luminescent [Au(SG)]n in isolable amounts (mg scale), usually not achieved by more conventional methods in solution. Then, ultrasmall oligomeric Au10-12(SG)10-12 nanoclusters were prepared by pH-triggered dissociation of [Au(SG)]n. The pH-stimulated dissociation of the Au(I)-glutathionate complex provides a time-efficient synthesis of oligomeric Au10-12(SG)10-12 nanoclusters, it avoids high-temperature heating or the addition of harmful reducing agent (e.g., carbon monoxide). Therefore, we present herein a new and eco-friendly methodology to access oligomeric glutathione-based gold nanoclusters, already finding applications in biomedical field as efficient radiosensitizers in cancer radiotherapy.

Mechanochemical synthesis of mononuclear gold(I) halide complexes of diphosphine ligands with tuneable luminescent properties.

A mechanochemical method is reported for the synthesis of Au(diphos)X complexes of diphosphine (diphos = XantPhos and N-XantPhos) ligands and halide ions (X = Cl and I). The Au(XantPhos)X (1: X = Cl; 2: X = I) and Au(N-XantPhos)Cl (3) complexes exhibited either yellowish green (1) or bluish green (2) emission, whereas 3 was seemingly non-emissive in the solid state at room temperature. Blue- (2B) and bluish green (2G) luminescent concomitant solvates of 2 were obtained by recrystallization. Luminescent colour changes from blue (2B) or bluish green (2G) to yellow were observed when these forms were subjected to mechanical stimulus, while the original emission colour can be recovered in the presence of solvent vapours. Moreover, the luminescence of 2B can be reversibly altered between blue and yellow by heating/cooling-cycles. These results demonstrate the power of mechanochemistry in the rapid (4 min reaction time), efficient (up to 98% yield) and greener synthesis of luminescent and stimuli-responsive gold(I) complexes.

Broadband measurement of true transverse relaxation rates in systems with coupled protons: application to the study of conformational exchange.

Accurate measurement of transverse relaxation rates in coupled spin systems is important in the study of molecular dynamics, but is severely complicated by the signal modulations caused by scalar couplings in spin echo experiments. The most widely used experiments for measuring transverse relaxation in coupled systems, CPMG and PROJECT, can suppress such modulations, but they also both suppress some relaxation contributions, and average relaxation rates between coupled spins. Here we introduce a new experiment which for the first time allows accurate broadband measurement of transverse relaxation rates of coupled protons, and hence the determination of exchange rate constants in slow exchange from relaxation measurements. The problems encountered with existing methods are illustrated, and the use of the new method is demonstrated for the classic case of hindered amide rotation and for the more challenging problem of exchange between helical enantiomers of a gold(i) complex.

An unusual case of childhood osteoarticular tuberculosis from the Árpádian Age cemetery of Gyorszentiván-Révhegyi tag (Gyor-Moson-Sopron county, Hungary).

Ancient human remains exhibiting bony changes consistent with osteoarticular tuberculosis (OATB) indicate that the disease has afflicted mankind for millennia. Nonetheless, not many pediatric OATB cases have been published in the paleopathological literature-from Hungary, only three cases have been described up to now. In our paper, we demonstrate a child (S0603) from the Árpádian Age cemetery of Gyorszentiván-Révhegyi tag (northwestern Hungary), who represents a unique case of OATB regarding both the pattern and severity of the observed bony changes. During the macromorphological and radiological investigations, the most serious alterations were discovered in the upper thoracic spine-the development of osteolytic lesions led to severe bone loss and consequent collapse and fusion of several adjacent vertebrae. The pathological process terminated in a sharp, rigid angular kyphosis. Disruption of the normal spine curvature resulted in consequent deformation of the whole thoracic wall-it became "rugby-ball-shaped". The overall nature and pattern of the detected alterations, as well as their resemblance to those of described in previously published archaeological and modern cases from the pre-antibiotic era indicate that they are most consistent with OATB. Based on the severity and extent of the lesions, as well as on the evidence of secondary healing, S0603 suffered from TB for a long time prior to death. Besides body deformation, OATB resulted in consequent disability in daily activities, which would have required regular and significant care from others to survive. It implies that in the Árpádian Age community of Gyorszentiván-Révhegyi tag, there was a willingness to care for people in need. Detailed archaeological case studies can give us a unique insight into the natural history and different presentations of OATB. Furthermore, they can provide paleopathologists with a stronger basis for diagnosing TB and consequently, with a more sensitive means of assessing TB frequency in past populations.

Unexpected formation of a fused double cycle trinuclear gold(i) complex supported by ortho-phenyl metallated aryl-diphosphine ligands and strong aurophilic interactions.

The first homoleptic trinuclear arylgold(i) complex, [Au3(L')2](NO3) (3), based on an ortho-phenyl metallated aryl-diphosphine ligand (L' = o-C6H4PPh(C15H10O)PPh2), has been obtained through a new thermolytic reaction of the corresponding diauracycle, [Au2(L)2](NO3)2 (L = xantphos). The formation of 3 involves activation of the ortho-phenyl C-H bond of the xantphos ligands. The presence of Au-C bonds in this new gold-diphosphine cluster is not its only remarkable feature, since it also displays two 12-membered rings fused together and a linear {Au3} chain with aurophilic interactions. Complex 3 exhibits strong sky-blue luminescence that can be assigned to a triplet metal-metal ((3)MM) transition partially mixed with a ligand-to-metal-metal charge transfer ((3)LMMCT) transition related to the aurophilic bonding. This [Au3(L')2](+) triauracycle also shows AIEE-activity, and is a selective luminescent chemosensor for metal ions.

Mechano-induced reversible colour and luminescence switching of a gold(i)-diphosphine complex.

A gold(i)-diphosphine simultaneously exhibits reversible mechanochromism and mechanochromic luminescence. The mechanical grinding can trigger a transformation from a neutral mononuclear structure exhibiting white colour and blue photoluminescence to an ionic dinuclear structure with intramolecular aurophilic interactions exhibiting yellow colour and red emission.

Anion-, Solvent-, Temperature-, and Mechano-Responsive Photoluminescence in Gold(I) Diphosphine-Based Dimers.

A series of [Au2 (nixantphos)2](X)2 (nixantphos=4,6-bis(diphenylphosphino)-phenoxazine; X=NO3, 1; CF3 COO, 2; CF3 SO3, 3; [Au(CN)2], 4; and BF4, 5) complexes that exhibit intriguing anion-switchable and stimuli-responsive luminescent photophysical properties have been synthesized and characterized. Depending on their anions, these complexes display yellow (3), orange (4 and 5), and red (1 and 2) emission colors. They exhibit reversible thermo-, mechano-, and vapochromic luminescence changes readily perceivable by the naked eye. Single-crystal X-ray studies show that the [Au2 (nixantphos)2](2+) cations with short intramolecular Au⋅⋅⋅Au interactions are involved as donors in an infinite N-H⋅⋅⋅X (X=O and N) hydrogen-bonded chain formation with CF3 COO(-) (2 C) and aurophilically linked [Au(CN)2](-) counterions (4 C). Both crystals show thermochromic luminescence; their room temperature red (2 C) and orange (4 C) emission turns into yellow upon cooling to 77 K. They also exhibit reversible mechanochromic luminescence by changing their emission color from red to dark (2 C), and orange to red (4 C). Compounds 1-5 also display reversible mechanochromic luminescence, altering their emission colors between orange (1) or red (2) to dark, as well as between yellow (3) or orange (4 and 5) to red. Detailed photophysical investigations and correlation with solid-state structural data established the significant role of NH⋅⋅⋅X interactions in the stimuli-responsive luminescent behavior.

Mechanochemical synthesis of crystalline and amorphous digold(I) helicates exhibiting anion- and phase-switchable luminescence properties.

For the first time, mechanochemical synthesis has been used for the preparation of crystalline and amorphous dinuclear gold(i) helicates, [Au2L2](X)2 (L = xantphos; X = CF3SO3, SCN, BF4 and PF6), that show anion- and phase-switchable luminescence properties. This solid-state approach provides strategies for developing switchable luminescent materials.

A versatile solvent-free mechanochemical route to the synthesis of heterometallic dicyanoaurate-based coordination polymers.

The solid-state mechanochemical method was proved to be a fast, simple, and efficient route to the synthesis of heterometallic [Au(CN)(2)]-based coordination polymers. Thus, a series of mixed-metal complexes, such as KCo[Au(CN)(2)](3), KNi[Au(CN)(2)](3), Cu(H(2)O)(2)[Au(CN)(2)](2), and Zn[Au(CN)(2)](2), was obtained by grinding stoichiometric amounts of K[Au(CN)(2)] and transition metal(II) chlorides. This solid-state method rapidly yields pure dicyanoaurate-based compounds, also in cases when the aqueous solution synthesis leads to an unseparable mixture of products. In addition, in some cases, the solid state reaction was faster than the corresponding solvent-based reaction. This mechanochemical method can be applied also to main group metals to obtain various cyanoaurate-based heterometallic coordination polymers, such as Me(2)Sn[Au(CN)(2)](2) and Ph(3)Sn[Au(CN)(2)]. For the 2:1 mixture of K[Au(CN)(2)] and Me(2)SnCl(2), the dramatic enhancement of the reaction rate by the presence of a minor amount of water was noticed. In Ph(3)Sn[Au(CN)(2)], as was revealed by single-crystal X-ray diffraction, each Ph(3)Sn unit is linked to two others by two Au(CN)(2) bridges via Sn-N bonds to form an infinite cyanide-bridged chain. There are no Au···Au contacts between the chains due to the sterical hindrance of the phenyl groups. A dehydrated blue Co[Au(CN)(2)](2) complex was obtained during grinding or heating of the moderate-pink Co(H(2)O)(2)[Au(CN)(2)](2) complex. This complex displays a vapochromic response when exposed to a variety of organic solvents, as well as water and ammonia vapors.

Guest escape and uptake in nonporous crystals of a gold(I) macrocycle.

The nonporous gold(I) diphosphine complex [Au(2)(cis-dppe)(2)](NO(3))(2) [1, cis-dppe = cis-1,2-bis(diphenylphosphino)ethylene] is robust enough to trap guests, but at the same time, it is flexible enough to allow guest release without destruction of its crystal lattice. This nonporous gold(I) compound 1 is also efficient at capturing and releasing carbon dioxide in a controlled manner.

[mu-4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene]bis[(trifluoroacetato)gold(I)] and its dichloromethane 0.58-solvate.

The dinuclear Au(I) complex containing the 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos) ligand and trifluoroacetate anions exists in a solvent-free form, [mu-4,5-bis(diphenylphosphino)-9,9-dimethylxanthene]bis[(trifluoroacetato)gold(I)], [Au(2)(C(2)F(3)O(2))(2)(C(39)H(32)OP(2))], (I), and as a dichloromethane solvate, [Au(2)(C(2)F(3)O(2))(2)(C(39)H(32)OP(2))].0.58CH(2)Cl(2), (II). The trifluoroacetate anions are coordinated to the Au(I) centres bridged by the xantphos ligand in both compounds. The Au(I) atoms are in distorted linear coordination environments in both compounds. The phosphine substituents are in a syn arrangement in the xantphos ligand, which facilitates the formation of short aurophilic Au...Au interactions of 2.8966 (8) A in (I) and 2.9439 (6) A in (II).

Synthesis and structure of a cyanoaurate-based organotin polymer exhibiting unusual ion-exchange properties.

We synthesized and structurally characterized the first cyanoaurate-based organotin polymer Me(3)Sn[Au(CN)(2)] (1), which exhibits unusual ion-exchange properties. In the structure of 1, the void space of the 2D grids formed via Au...Au bonding is filled by arrays of zigzag chains joined by weak Au...Au interactions. Interestingly, the practically insoluble polymer 1 shows unusual ion-exchange properties. The polymer Me(2)Sn[Au(CN)(2)](2) (2) was obtained in the metathesis reaction of 1 with Me(2)SnCl(2). Compound 2 displays cyanide-bridged uninodal four-connected 3D nets with 6(5).8 topology corresponding to the CdSO(4) prototype. Interestingly, 2 can be converted back into 1 by metathesis with Me(3)SnCl. Moreover, we performed a series of metal-exchange experiments in which 1 was soaked in aqueous solutions of bivalent transition-metal cations M(2+) (M = Co, Ni, Cu, Zn). As a result, 1 was completely converted into transition-metal cyanoaurates. To our knowledge, this represents the first study revealing the metal-exchange properties of a cyanoaurate-based heterometallic polymer.

Solvent-assisted spontaneous resolution of a 16-membered ring containing gold(I) showing short Au...Au aurophilic interaction and a figure-eight conformation.

The achiral 4,6-bis(diphenylphosphino) phenoxazine (nixantphos) ligand was used to synthesize a gold(I) complex, [Au2(nixantphos)2](NO3)2, containing a 16-membered [Au2(nixantphos)2](+2) cationic ring in a chiral figure-eight conformation. The single crystal X-ray diffraction analysis of [Au2(nixantphos)2](NO3)2.3MeOH.H2O (1) and [Au2(nixantphos)2](NO3)2.4MeCN (2) revealed a solvent-assisted spontaneous resolution of the [Au2(nixantphos)2](NO3)2 complex. By changing the nature of the solvent, homochiral hydrogen bonded helices (1) and heterochiral hydrogen bonded monomers (2) were obtained. Multinuclear NMR spectroscopy showed the evidence of chemical exchange phenomenon related to the interconversion of the enantiomeric skeletons of the 16-membered macrocycle in solution. The existence of the Au...Au aurophilic interaction was confirmed by the analysis of the spin-system in the (31)P NMR spectrum.

Conformational analysis of a helically distorted gold(I) macrocycle derived from xantphos: evidence for the aurophilic Au--Au interaction from NMR.

Variable-temperature solution (1)H- and (31)P-NMR experiments are reported for [Au(2)(xantphos)(2)](NO(3))(2) gold(I) complex incorporating a 16-membered Au(2)P(4)C(8)O(2) macrocycle derived from the 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (xantphos) ligand. These NMR studies provide detailed structural information about its solution structure in comparison to the solid-state structure available from single crystal X-ray diffraction. Two-dimensional (1)H-NOESY spectroscopy at low temperatures allowed the full assignment of proton resonances, which are severely exchange-broadened at room temperature. The (1)H--(1)H spatial connectivities of the large number of non-equivalent protons unravel the complete stereochemistry of the gold(I) macrocycle in its symmetrically twisted conformation. Chemical exchange between particular proton pairs has allowed understanding the molecular dynamics and ruled out formation of coordination oligomers. Spectral analysis of the unique phosphorous AA'BB' spin system has revealed three-bond (31)P--(31)P scalar couplings mediated through the Au--Au bond, and has confirmed the existence of the aurophilic contact in low-temperature solutions. The solution (13)C and (31)P spectra are compared to the solid state (31)P-MAS and (13)C--CP/MAS spectra, where signal doubling effects due to the crystal packing have been discovered.

Multifocal ERG reveals several patterns of cone degeneration in retinitis pigmentosa with concentric narrowing of the visual field.

PURPOSE: To analyze multifocal ERGs (mfERGs) in patients with retinitis pigmentosa (RP), with constricted visual fields and visual acuity satisfactory for steady fixation. METHODS: The mfERGs of 86 eyes of 43 patients with various forms of inheritance and durations of RP were analyzed. A retinal scanning system with a 20-in. monitor was used to map central cone function. Electrical signals of the retina were detected by using DTL fiber electrodes. RESULTS: The site of the best response density of the mfERGs in the patients with RP was found in a central or eccentric position of the trace array. Depending on the position of the best response density in the two eyes, the patients were categorized into three groups. In the first group, the best response density was recorded from the central hexagon in both eyes, producing a central peak surrounded by very low responses in the three-dimensional presentation. In the second group of patients, the best responses were found to correspond to the central hexagon on only one side. In the fellow eye, however, the best response density appeared to be in an eccentric position. The patients in the third group did not present a central peak in the mfERG on either side. In scattered parts of the trace arrays, several acceptable responses were observed in all three groups that might represent patches of functioning retinal cone receptors. CONCLUSIONS: The results suggest highly variable central responses and groups of cones with preserved function in areas previously considered nonresponsive. The high variability of the central responses could be a result of variable foveal cone density, with differences in inheritance- and duration-related cone degeneration at the time of the examination. The authors stress the value of step-by-step analysis of the trace array of the mfERGs, which can reveal the still-functioning groups of cones.

Preparation and structural characterization of trimethyltin(IV) tropolonate. Investigation of a rare methyl-migrational dismutation in the solution, solid and liquid states.

The synthesis and structural characterisation, by low temperature X-ray diffraction and solid-state NMR, of the highly reactive monomeric Me(3)Sn(trop) (1) complex has been studied; 1 rearranges into Me(2)Sn(trop)(2) (2) and Me(4)Sn by methyl-transfer dismutation. Based on the NMR kinetic data it appears that complex demethylates faster in the solid and liquid than in dilute CDCl(3) solution, but with a slower rate than in dilute CD(3)OD solution.

Synthesis and solution- and solid-state characterization of gold(I) rings with short Au...Au interactions. Spontaneous resolution of a gold(I) complex.

We report the synthesis and solution- and solid-state characterization of gold(I) rings with short 1,9-transannular Au...Au interactions. The 9- and 16-membered gold(I) rings were prepared by reacting 9,9-dimethyl-4,5-bis(diphenylphosphino)-xanthene and (Me2S)AuCl in the presence of AgNO3 in the molar ratio of 1:0.5:1 and 1:1:1, respectively. X-ray crystallographic measurements in conjunction with solution X-ray diffraction and NMR methods have been used to determine the structure of gold(I) rings, and we also gained insight into the dynamics. The nine-membered gold(I) ring is chiral, and the crystal contains only one of the two enantiomers, either right- or left-handed. To the best of our knowledge this represents the first example of crystallization-induced spontaneous resolution of a binuclear gold(I) cycle. The 16-membered ring with 1,9-transannular Au...Au interaction is in a figure-eight conformation.

Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study.

Cytokines have been detected by ELISA in a variety of body fluids. Recycling immunoaffinity chromatography (RIC) coupled with laser-induced fluorescence detection is a highly sensitive and specific method, which allows simultaneous measurements of many analytes in small volumes of biological fluids. This method has been applied to plasma, cervical secretions and other body fluids, but has not previously been applied to sweat. The aim of this study was to validate the RIC methodology in sweat for measurements of IL-1alpha, IL-1beta, IL-6, TNF-alpha, IL-8 and TGF-beta. Two sweat patches were applied for 24 h on the torso, and blood was collected at one time point during this period in nine healthy women. Cytokines were measured in paired samples of plasma and sweat. Cytokines were detected in sweat in similar concentrations to plasma. Linear regression analysis confirmed that sweat levels of these cytokines accounted for a large percentages of variance in plasma levels: IL-1alpha (R2 = 0.70, p = 0.005), IL-1beta (R2 = 0.79, p = 0.003), IL-6 (R2 = 0.52, p = 0.03), TNF-alpha (R2 = 0.95, p < 0.0001), IL-8 (R2 = 0.81, p = 0.001) and TGF-beta (R2 = 0.94, p = 0.0003). These findings indicate that cytokine levels measured in sweat are informative of circulating levels and that sweat patches combined with RIC represents a viable non-invasive method to measure cytokines in ambulatory settings over time. This method is unobtrusive and requires minimal active compliance on the part of the subjects being studied, without pain or stress. This approach can open a new generation of studies to address the effects of environmental factors on immune responses in a wide range of different settings.

Demethylation of the [Me3Sn(PhN2O2)]4 tetramer into dimeric [Me2Sn(PhN2O2)2]2: a thermally induced methyl-transfer between supramolecules.

The single crystals of tetrameric [Me3Sn(PhN2O2)]4 (1) supramolecule demethylates into single crystals of [Me2Sn(PhN2O2)2]2 dimer (2) and volatile Me4Sn, as a result of a crystal-to-crystal supramolecular structural transformation, which occurs upon heating and it is accompanied by a significant change of the molecular and crystal structures.