Analysis of unknown (unlabeled/mislabeled) drug products for active pharmaceutical ingredients and related substances by an international mail facility satellite laboratory equipped with rapid screening devices.

Two chemists employed a three-device rapid screening "toolkit" consisting of a handheld Raman spectrometer, transportable mass spectrometer, and portable Fourier transform infrared (FT-IR) spectrometer at an international mail facility (IMF) satellite laboratory to examine unknown (unlabeled/mislabeled) products for the presence of active pharmaceutical ingredients (APIs). Phase I of this project previously demonstrated that this toolkit was the most effective collection of instruments for identifying APIs in product types collected at IMFs during a nationwide mail blitz and Phase II of this project previously demonstrated that results generated using the toolkit during a satellite laboratory pilot program were as reliable as those generated by a full-service library when two or more of these instruments identify an API. This study (Phase III) described the results of the satellite laboratory toolkit during production mode and encompassed the period ranging from June 2021 through December 2022. During this study, a total of 858 products were examined on-site at the IMF. The satellite laboratory yielded conclusive results for 726 (84.6%) products, which were used to support regulatory action, and identified 132 (15.4%) products that required additional full-service laboratory analyses due to inconclusive results. The satellite and full-service laboratory verified/confirmed at least one API/related substance in 617 (71.9%) products. A total of 709 APIs/related substances were found in the 617 products, and 202 of these 709 compounds were unique/different. Overall, during Phases I through III of this program, 350 different substances have been identified in products collected at IMFs.

Rapid screening of 2-benzylbenzimidazole nitazene analogs in suspect counterfeit tablets using Raman, SERS, DART-TD-MS, and FT-IR.

Developing methods to rapidly screen for novel synthetic 2-benzylbenzimidazole opioids, also known as nitazenes, has become increasingly important due to their high potency. These compounds have potency comparable or exceeding that of fentanyl by up to 10 times and have been implicated in approximately 5% of all drug overdose deaths in the United States in 2021. This paper details the authenticity determination of suspect tablets and the identification of three nitazene analogs (N-pyrrolidino etonitazene, isotonitazene, and etodesnitazene) in suspect tablets seized at a mail facility using Raman and surface-enhanced Raman scattering (SERS) with handheld devices, portable Fourier transform infrared spectrometer (FT-IR), and a direct analysis in real-time ambient ionization coupled to a thermal desorption unit and a mass spectrometer (DART-TD-MS). These methods are rapid and excellent for screening opioids in suspect tablets but could not fully determine the exact structure of some of the nitazene analogs present due to spectral similarities or similar fragmentation patterns. Liquid chromatography-mass spectrometry (LC-MS) confirmed the presence of these nitazene compounds in addition to other opioids/drugs that were in trace quantities. The quantitative high-performance liquid chromatography coupled with ultraviolet (HPLC-UV) detection experiments determined that the suspect tablets contained an average of 0.817 mg of N-pyrrolidino etonitazene per tablet. The results obtained reveal that the simultaneous deployment of these complementary and orthogonal portable analytical techniques as part of a workflow allows suspect tablets to be screened and nitazene-type drugs to be identified in suspect counterfeit tablets at remote sampling sites.

Rapid detection of active pharmaceutical ingredients in drug products collected at an international mail facility by a satellite laboratory using a "toolkit" consisting of a handheld Raman spectrometer, portable mass spectrometer and portable FT-IR spectrometer.

A satellite laboratory "toolkit" consisting of a handheld Raman spectrometer, portable direct analysis in real-time mass spectrometer (DART-MS) and portable Fourier transform infrared (FT-IR) spectrometer was employed to examine 926 pharmaceutical, unknown and dietary supplement products collected at an international mail facility (IMF) for the presence of declared and undeclared active pharmaceutical ingredients (APIs) over the course of 68 working days. The toolkit successfully identified over 650 APIs, including over 200 unique APIs, using two or more devices. The performance of each individual device, and toolkit as a whole, were evaluated on all products and a subset of the products was forwarded to full-service laboratories for confirmatory analysis to determine false positive and false negative rates of the toolkit. The subset consisted of seven negative items (those not found to contain APIs using the toolkit) and 124 positive items (those found to contain at least one API using the toolkit). Overall, no false positives were detected in the negative items and only four false negatives and five false positives were detected in the positive items. Regarding the positive items, 119 of the 124 items were found to contain at least one API using at least two toolkit devices; each of these APIs were confirmed by a full-service laboratory. Furthermore, 90.2% of the APIs found by confirmatory laboratory analysis were detected by at least two toolkit devices. Based on these metrics and the fact that no false positives were detected by more than one device, it was concluded that when the toolkit detects and subsequently verifies/confirms an API using two or more devices, the results are as reliable as those generated by a full-service laboratory.

Screening suspect pharmaceuticals for illicit designer benzodiazepines using raman, SERS, and FT-IR prior to comprehensive analysis using LC-MS.

The emergence of illicit designer benzodiazepines with high dependency and no approved clinical use are of great US public health concern. Due to the increasing numbers of illicit designer benzodiazepines encountered in the US supply chain, there is a need to develop robust analytical methods that can rapidly detect these chemicals. Suspect counterfeit tablets, powders, or liquid formulations were first screened using Raman spectroscopy and surface-enhanced Raman scattering spectroscopy (SERS) for the presence of legal or illicit benzodiazepines, and then further analyzed using Fourier-transform infrared (FT-IR) spectroscopy and liquid chromatography with tandem mass spectrometric detection (LC-MS). Several microextraction procedures were developed and used to extract benzodiazepines from samples prior to SERS, FT-IR, and LC-MS analysis. Conventional Raman analyses using handheld Raman spectrometers afforded the ability to examine samples through enclosed plastic bags but were only able to detect high concentrations of various benzodiazepines in the suspect samples. The developed SERS methods were sufficient for detecting at least one benzodiazepine in the low-dose suspect samples, thereby allowing prioritization using other analytical tools that require more sample preparation and time-consuming analyses. The use of FT-IR spectroscopy coupled with extraction and spectral subtraction was found to be selective to multiple benzodiazepines and various excipients in the analyzed samples. This study demonstrated that the developed SERS and FT-IR procedures could be used in satellite laboratories to screen suspect packages at ports of entry and prioritize samples for additional laboratory-based analyses in an effort to prevent dangerous and illicit pharmaceutical products from reaching the US supply chain.

Electrophoresis on a polyester thread coupled with an end-channel pencil electrode detector.

We present the design and characterization of a low cost, thread-based electrophoretic device with integrated electrochemical detection. The device has an end-channel pencil graphite electrode placement system for performing electrochemical detection on the thread electrophoresis platform with direct sample pipetting onto the thread. We also established the use of methylene blue and neutral red as a pair of reference migration markers for separation techniques coupled with electrochemical detection, as they have different colors for visual analysis and are both electroactive. Importantly, neutral red was also found to migrate at a similar rate to the EOF, indicating that it can be used as a visual identifier of EOF. The utility of our system was demonstrated by electrophoretic separation and electrochemical detection of physiologically relevant concentrations of pyocyanin in a solution containing multiple electroactive compounds. Pyocyanin is a biomarker for the detection of pathogenic Pseudomonas aeruginosa and has a redox potential that is similar to that of methylene blue. The system was able to effectively resolve methylene blue, neutral red, and pyocyanin in less than 7 min of electrophoretic separation. The theoretical limit of detection for pyocyanin was determined to be 559 nM. The electrophoretic mobilities of methylene blue (0.0236 ± 0.0007 mm2 /V·s), neutral red (0.0149 ± 0.0007 mm2 /V·s), and pyocyanin (0.0107 ± 0.0003 mm2 /V·s) were also determined.

Rapid determination of eight benzodiazepines in suspected counterfeit pharmaceuticals using surface-enhanced Raman scattering with handheld Raman spectrometers.

The excessive prescription of benzodiazepines is putting more people at risk of dependence on these drugs and is exacerbating the fatal overdose toll of opioids. A rapid and sensitive SERS method has been developed for trace detection of select benzodiazepines in low-dosage suspect counterfeit tablets, capsules, and injectable solutions using two different portable handheld Raman spectrometers equipped with either a 785-nm laser or a 1064-nm laser. A total of 169 samples and blanks were examined using five handheld Raman spectrometers, which provided data set of 729 examinations. The extraction/SERS procedures yielded true positive rates above 90% for alprazolam, diazepam, and midazolam using the 1064-nm device and yielded true positive rates above 95% for alprazolam, clonazepam, diazepam, estazolam, midazolam, and temazepam using the 785-nm device; however, the extraction/SERS procedures yielded true positive rates below 60% for lorazepam and triazolam. The minimum concentration (Cmin ) of the benzodiazepine standards that reproducibly yielded a positive match ranged from 1 to 10 µg/ml using the 1064-nm laser device and from 0.5 to 50 µg/ml using the 785-nm laser device. For the analysis of authentic and suspect counterfeit tablets containing these benzodiazepines, the measured Cmin ranged between 10 and 15 µg per tablet or capsule for 1064-nm laser device and 1-100 µg per tablet or capsule for 785-nm laser device. The developed methods are simple, rapid, and ideal for screening suspect benzodiazepine-containing pharmaceutical products at satellite laboratories located within or near international mail facilities and express courier hubs.

Evaluation of "Toolkit" consisting of handheld and portable analytical devices for detecting active pharmaceutical ingredients in drug products collected during a simultaneous nation-wide mail blitz.

A "toolkit" consisting of a handheld Raman spectrometer equipped with a 1064 nm laser, a portable Fourier transform infrared (FT-IR) spectrometer and a portable direct analysis in real-time mass spectrometer (DART-MS) was employed in a laboratory setting to examine 82 representative products collected during a nationwide mail blitz for the presence of APIs. These results were compared to those obtained using laboratory-based methods; 8 of the products were not found to contain APIs and 74 of the products were found to contain a total of 88 APIs (65 of the 88 APIs were unique). The individual performance of each device and combined performance of the three-device toolkit were evaluated with regard to true positives, true negatives, false positives and false negatives. Using this toolkit, 81 (92.0 %) of the APIs were detected by at least one technique and 47 (64.8 %) of the APIs were detected by at least two techniques. Seven false negatives (8.0 %) were encountered and while the toolkit yielded 12 false positives, no false positives were detected by more than one technique. Overall, this study demonstrated that when the toolkit detects an API using two or more devices, the results are as reliable as those generated by a full-service laboratory.

Trace level detection of select opioids (fentanyl, hydrocodone, oxycodone, and tramadol) in suspect pharmaceutical tablets using surface-enhanced Raman scattering (SERS) with handheld devices.

The opioid crisis in the USA has resulted in over 702,000 overdose fatalities between 1999 and 2017 and can be attributed to over-prescription of opioids and abuse of synthetic opioids in combination with other illicit drugs. A rapid and sensitive SERS method has been developed for trace detection of opioids including fentanyl, hydrocodone, oxycodone, and tramadol in low-dosage suspect tablets using two different handheld Raman spectrometers equipped with 785 and 1064 nm lasers. The method involves a micro-extraction procedure using 10% methanol in deionized water, followed by filtration and addition of colloidal silver and aqueous KBr, resulting in a mixture that can be measured directly via a glass vial. The lowest concentration (Cmin ) of fentanyl, tramadol, oxycodone, and hydrocodone standards that yielded a positive match was 250 ng/ml, 5, 10, and 10 µg/ml using the 1064 nm laser device and 100 ng/ml, 1 µg/ml, 500 ng/ml, and 750 ng/ml using the 785 nm laser device, respectively. For the analysis of suspect tablets containing these opioids, the Cmin ranges between 5 and 75 µg/ml for 1064 nm laser device and 1 and 50 µg/ml for 785 nm laser device. The overall positive identification rate for all the opioids studied in the suspect counterfeit tablets analyzed ranged from 80% to 100%. The use of SERS for rapid chemical identification at remote sampling sites, such as international mail facilities (IMFs) and express courier hubs (ECHs), provides a rugged, simple, and practical method applicable for point-of-entry sampling and analysis.

Evaluation of Suspected Counterfeit Pharmaceutical Tablets Declared to Contain Controlled Substances Using Handheld Raman Spectrometers.

This study describes the performance of handheld Raman devices for determining whether suspect pharmaceutical tablets declared to contain controlled substances were consistent with authentic (CWA) or not consistent with authentic (NCWA) tablets using a simple, rapid, field-friendly method capable of being used by nonexperts. Twenty-five authentic products and 84 known NCWA tablets were examined using three "parent" devices for a total of 327 analyses. On average, the parent devices yielded a true pass rate of 100%, a true fail rate of 98.4%, a false pass rate of 1.6%, and a false fail rate of 0%. The methods/libraries were then transferred to 13 identical "daughter" devices, which were used to examine 10 suspect finished dosage forms in duplicate (six known NCWA tablets and four authentic tablets) for a total of 260 measurements. On average, the daughter devices had a true pass rate of 100%, a true fail rate of 95.5%, a false pass rate of 4.5%, and a false fail rate of 0.0%. These data demonstrate that the parent-daughter electronic transfer method was successful, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices. The methods can then be used to (i) prioritize samples for additional testing using other more time-consuming laboratory-based techniques needed to detect and quantify active ingredients and (ii) help support the interdiction of dangerous tablets at ports of entry, thereby preventing them from reaching the supply chain.

Biosample Concentration Using Microscale Forward Osmosis with Electrochemical Monitoring.

We report the design and operation of an integrated microfluidics system that uses cellulose ester dialysis membranes coupled with disposable carbon and copper electrodes for monitoring and concentration of microliter scale biofluid samples. Dialysis membranes are typically used for buffer exchange, but in this work, membranes with 100-500 Da MWCO were evaluated for feasibility in concentrating small volume samples. This is an alternative to the use of centrifugation, ultrafiltration, and evaporative methods, where quantitative inline monitoring of sample concentration is challenging. The impact of draw solution used, osmotic concentration gradient, pH, and temperature were studied for the optimized concentration of bodily fluids. A system using sucrose in the draw solution generated the best results, with water removal rates of 0.023 mL min-1. PBS, urine, and saliva samples were concentrated up to 20-fold (PBS), 15-fold (urine), and 5-fold (saliva) in less than 3 h. The osmotic system further showed a 5-fold increase in the electrochemical signal for detecting pyocyanin, a biomarker for early diagnostics of the Pseudomonas aeruginosa pathogen in urine and saliva samples. Overall, the osmotic system can be easily integrated with point of care diagnostic systems for low cost improvement in signal amplification and limit of detection.

Synthesis, characterization, DFT calculations, and electrochemical comparison of novel iron(ii) complexes with thione and selone ligands.

Thione- and selone-containing compounds and their metal complexes show promise as antioxidants, as antithyroid drugs, and for applications in lasers and blue light-emitting diodes. Although Cu(i/ii), Co(ii), Ag(i), and Zn(ii) coordination to thione and selone ligands has been broadly studied and Fe(ii) plays an important role in oxidative damage, very few iron-thione complexes and no iron-selone complexes are reported. Novel Fe(ii)-containing thione and selone complexes of the formulae FeL2Cl2, [FeL2(CH3CN)2](2+), and [FeL4](2+), and {FeL'Cl2}n, (L = N,N'-dimethylimidazole selone (dmise), and thione (dmit); L' = bis(thioimidazolyl)ethane (ebit) and bis(selenoimidazolyl)ethane (ebis)) have been synthesized and characterized. Structures of Fe(dmise)2Cl2, Fe(dmit)2Cl2, [Fe(dmit)4][BF4]2, [Fe(dmise)4][BF4]2, and {Fe(ebit)Cl2}n were determined by X-ray crystallography. All Fe(ii) centers adopt a distorted tetrahedral coordination geometry with Fe-S distances ranging from 2.339(1) to 2.397(1) Å and F-Se distances ranging from 2.453(1) to 2.514(1) Å. Density functional theory optimized structures of FeL2Cl2, [FeL2(CH3CN)2](2+), and [FeL4](2+) are consistent with experimental results and suggest that thiones and selones are π-donor ligands that coordinate through their zwitterionic resonance structures. Thione and selone coordination to Fe(ii) lowers the Fe(ii/iii) reduction potential, with a greater decrease for Fe(ii)-bound dmise than Fe(ii)-bound dmit. Dmit and dmise ligand-based oxidation potentials also significantly increase upon Fe(ii) binding compared, indicating that bound thione and selone ligands will undergo oxidation prior to Fe(ii). The synthesis of these complexes suggests that iron coordination by thione and selone ligands may occur in vivo and may contribute to the protective antioxidant properties of sulfur and selenium.

Dinuclear copper(I) complexes with N-heterocyclic thione and selone ligands: synthesis, characterization, and electrochemical studies.

The synthesis, characterization, and structures of a series of homoleptic and heteroleptic copper(I) complexes supported by N-heterocyclic chalcogenone ligands is reported herein. The quasi-reversible Cu(II/I) reduction potentials of these copper complexes with monodentate (dmit or dmise) and/or bidentate (Bmm(Me), Bsem(Me), Bme(Me), Bsee(Me)) chalcogenone ligands are highly dependent upon the nature and number of the donor groups and can be tuned over a 470 mV range (-369 to 102 mV). Copper-selone complexes have more negative Cu(II/I) reduction potentials relative to their thione analogs by an average of 137 mV, and increasing the number of methylene units linking the heterocyclic rings in the bidentate ligands results in more negative reduction potentials for their copper complexes. This ability to tune the copper reduction potentials over a wide range has potential applications in synthetic and industrial catalysis as well as the understanding of important biological processes such as electron transfer in blue copper proteins and respiration.

Oxidation of biologically relevant chalcogenones and their Cu(I) complexes: insight into selenium and sulfur antioxidant activity.

Hydroxyl radical damage to DNA causes disease, and sulfur and selenium antioxidant coordination to hydroxyl-radical-generating Cu(+) is one mechanism for their observed DNA damage prevention. To determine how copper binding results in antioxidant activity, biologically relevant selone and thione ligands and Cu(+) complexes of the formula [Tpm*Cu(L)](+) [Tpm* = tris(3,5-dimethylpyrazolyl)methane; L = N,N'-dimethylimidazole selone or thione] were treated with H2O2 and the products analyzed by (1)H, (13)C{(1)H}, and (77)Se{(1)H} NMR spectroscopy, mass spectrometry, and X-ray crystallography. Upon H2O2 treatment, selone and thione binding to Cu(+) prevents oxidation to Cu(2+); instead, the chalcogenone ligand is oxidized. Thus, copper coordination by sulfur and selenium compounds can provide targeted sacrificial antioxidant activity.

Hydrothermal synthesis and spectroscopic properties of a new glaserite material, K3RE(VO4)2 (RE = Sc, Y, Dy, Ho, Er, Yb, Lu, or Tm) with potential lasing and optical properties.

A new series of materials of the glaserite family with the general formula K(3)RE(VO(4))(2)(RE = Sc, Y, Dy, Ho, Er, Tm, Yb, and Lu) have been hydrothermally synthesized using 10 M K(2)CO(3) at 560 °C and characterized by single crystal X-ray diffraction (XRD), powder XRD, differential thermal analysis/thermogravimetric analysis (DTA/TGA), energy-dispersion X-ray (EDX), Raman, infrared, and absorption spectroscopy. All the compounds crystallize in the trigonal P3̅m1 space group (No. 164), and their structures contain VO(4) tetrahedra, REO(6) octahedra, and two different K(1)O(10) and K(2)O(12) polyhedra. The spectroscopic properties of Nd(3+), Yb(3+), or Er(3+) doped K(3)RE(VO(4))(2) (RE = Y or Lu) are also reported, and the results obtained show that these compounds have promising potential as new laser host materials.

Hydrothermal synthesis and comparative coordination chemistry of new rare-earth V4+ compounds.

Several new hydrated rare earth vanadates and rare earth oxy-vanadates have been synthesized using hydrothermal techniques and characterized using single crystal and powder X-ray diffraction and infrared and UV-vis absorption spectroscopies. The hydrated rare earth vanadates adopt the space group P2(1)/m with general formula A(3)VO(5)(OH)(3) (A = Y (1), Dy (2), or La (3)) and contain anionic distorted square pyramidal [VO(5)](-6) units and AO(7) and AO(8) polyhedra. The oxy-vanadates with the general formula A(2)O(VO(4)) (A = Y (4), Dy (5; 6), or Yb (7)) form two polymorphs in either P2(1)/c or C2/c space groups and contain anionic tetrahedral [VO(4)](-4) units and nonvanadium bonded O(2-) anions in distorted [OA(4)] tetrahedra. In all cases, the vanadium ion is in the tetravalent oxidation state, and its original source was the trace V(4+) impurities in YVO(4). The observed vanadyl and equatorial vanadium-oxygen bond lengths about the square pyramid in compounds 1-3 and the tetrahedral vanadium coordination found in compounds 4-7 are unusual for V(4+). The electronic and vibrational spectra are also reported and correlated with the appropriate coordination environment.

Investigating the copper coordination, electrochemistry, and Cu(II) reduction kinetics of biologically relevant selone and thione compounds.

Selenium- and sulfur-containing compounds can act as antioxidants by binding copper. To determine how this copper coordination results in the observed antioxidant activity, biologically relevant Cu(+) and Cu(2+) complexes with the formulae [Cu(dmit)(3)](+) (3), [Cu(dmise)(4)](+) (4a), and [Tpm(iPr)Cu(MISeox)](2+) (6) (dmise = N,N'-dimethylimidazole selone; dmit = N,N'-dimethylimidazole thione; MISeox = bis(1-methylimidazolyl)diselenide; Tpm(iPr) = tris(1,3-diisopropylpyrazolyl)methane) were synthesized, characterized, and their structures determined by single-crystal X-ray crystallography. In addition, kinetic studies using UV-vis spectroscopy indicate that dmise reduces Cu(2+) to Cu(+) three times faster than dmit. Coordination of dmise and MISeox to copper also results in more negative Cu(2+/+) reduction potentials (-373 mV and -503 mV) compared to dmit (-217 mV). These results highlight the different complexation behaviors and reactivities of analogous selone- and thione-containing compounds, traits which likely influence their antioxidant activity.

The diselanylbis(1,3-dimethyl-1H-imidazol-3-ium) dication stabilized by the polymeric catena-pentachloridotricuprate(I) anion.

In the title compound, catena-poly[diselanylbis(1,3-dimethyl-1H-imidazol-3-ium) [µ(3)-chlorido-tetra-µ(2)-chlorido-tricuprate(I)]], {(C(10)H(16)N(4)Se(2))[Cu(3)Cl(5)]}(n), the diselenide dication is stabilized by catena-[Cu(3)Cl(5)](2-) anions which associate through strong Cu-Cl bonds [average length = 2.3525 (13) Å] to form polymeric chains. The polymeric [Cu(3)Cl(5)](2-) anion contains crystallographically imposed twofold rotation symmetry, with distorted trigonal-planar and tetrahedral geometries around the two symmetry-independent Cu atoms. Likewise, the Se-Se bond of the cation is centered on a twofold rotation axis.

Synthesis, characterization, and DFT studies of thione and selone Cu(I) complexes with variable coordination geometries.

Coordination of Cu(I) halides with N,N'-dimethylimidazole selone (dmise) and thione (dmit) ligands was examined by treating CuX (X = Cl, Br, I) with one or two equivalents of dmise or dmit. The reaction of CuI and CuBr with one molar equivalent of dmise results in unusual selenium-bridged tetrameric Cu(4)(µ-dmise)(4)(µ-X)(2)X(2) copper complexes with average Cu-Se bond lengths of 2.42 Å and a Cu(2)(µ-X)(2) core (X = I (1) or Br (6)) that's in a rhomboidal structure. The reaction of CuX (X = Cl, Br, and I) with two equivalents of dmit or dmise results in trigonal planar Cu(I) complexes of two different conformations with the formula Cu(dmit)(2)X (3a, 3b, 4, and 7) or Cu(dmise)(2)X (2, 5, and 8) with average Cu-S and Cu-Se bond lengths of 2.23 Å and 2.34 Å, respectively. The coordination geometry around the copper center in complexes 1 to 8 is determined by the type of halide and chalcogenone ligand used, intramolecular π-π interactions, and short contact interactions between X-H (X = I, Br, Cl, Se or S). The theoretical DFT calculations are in good agreement with experimental X-ray structural data and indicate that dmise ligands are required for formation of the tetrameric complexes 1 and 6. Electrochemical studies show that the trigonal copper selone complexes have more negative potentials relative to analogous copper thione complexes by an average of 108 mV.

Probing the antioxidant action of selenium and sulfur using Cu(I)-chalcogenone tris(pyrazolyl)methane and -borate complexes.

Hydroxyl radical generated from the reaction of Cu(+) with hydrogen peroxide results in oxidative DNA damage, and this damage is implicated in aging, cancer, and many other diseases. Selenium- and sulfur-containing compounds can act as antioxidants, and coordination of selenium and sulfur to copper is one explanation for this antioxidant activity. To determine how copper coordination results in antioxidant activity, biologically relevant tris(pyrazolyl)methane and borate Cu(+) complexes of the formulas Tp*Cu(L) and [Tpm(R)Cu(L)](+), where (L = N, N'-dimethylimidazole selone, dmise; N, N'-dimethylimidazole thione, dmit; Tp* = hydrotris(3,5-dimethylpyrazolyl)borate; Tpm(R) = tris(pyrazolyl)methane, R = H; Tpm, R = Me; Tpm*, R = iPr; Tpm(iPr)), have been synthesized and characterized. The structures of complexes Tp*Cu(Dmit), Tp*Cu(dmise), [Tpm(R)Cu(dmise)][BF(4)], and [Tpm(R)Cu(Dmit)][BF(4)] (where R = H; Tpm, R = Me; Tpm*, R = iPr; Tpm(iPr)) were determined by X-ray crystallography. All the Cu(+) centers adopt distorted tetrahedral coordination geometry, and Cu-Se and Cu-S distances for all the complexes are approximately 2.30 Å, and 2.20 Å, respectively. The effects of counterion and steric bulk at the 3 and 5 positions of the pyrazolyl ring on the structural and spectroscopic properties are discussed. Selone or thione coordination to copper significantly alters the Cu(+/2+) redox potential: Cu-selone complexes have Cu(2+/+) potentials from -283 to -390 mV, whereas those of Cu-thione complexes range from 70 to -232 mV versus NHE. The Cu-selone complexes have Cu(2+/+) potentials near or below that of the cellular reductant NADH (-324 mV). Thus, selenium and sulfur coordination to copper in biological systems may prevent the Cu(2+) reduction by NADH required for the catalytic formation of damaging hydroxyl radical.

Metallic single-walled carbon nanotubes for conductive nanocomposites.

This article reports an unambiguous demonstration that bulk-separated metallic single-walled carbon nanotubes offer superior performance (consistently and substantially better than the as-produced nanotube sample) in conductive composites with poly(3-hexylthiophene) and also in transparent conductive coatings based on PEDOT:PSS. The results serve as a validation on the widely held view that the carbon nanotubes are competitive in various technologies currently dominated by conductive inorganic materials (such as indium tin oxide).