Organometallic Research Articles

Assessment of the applicability of DFT methods to [Cp*Rh]-catalyzed hydrogen evolution processes.

The present computational study provides a benchmark of density functional theory (DFT) methods in describing hydrogen evolution processes catalyzed by [Cp*Rh]-containing organometallic complexes. A test set was composed of 26 elementary reactions featuring chemical transformations and bonding situations essential for the field, including the emerging concept of non-innocent Cp* behavior. Reference values were obtained from a highly accurate 3/4 complete basis set and 6/7 complete PNO space extrapolated DLPNO-CCSD(T) energies. The performance of lower-level extrapolation procedures was also assessed. We considered 84 density functionals (DF) (including 13 generalized gradient approximations (GGA), nine meta-GGAs, 33 hybrids, and 29 double-hybrids) and three composite methods (HF-3c, PBEh-3c, and r2SCAN-3c), combined with different types of dispersion corrections (D3(0), D3BJ, D4, and VV10). The most accurate approach is the PBE0-DH-D3BJ (MAD of 1.36 kcal mol-1) followed by TPSS0-D3BJ (MAD of 1.60 kcal mol-1). Low-cost r2SCAN-3c composite provides a less accurate but much faster alternative (MAD of 2.39 kcal mol-1). The widely used Minnesota-family M06-L, M06, and M06-2X DFs should be avoided (MADs of 3.70, 3.94, and 4.01 kcal mol-1, respectively).

Coordination Complexes of Cobalt with Pyrazole-Based Ligands and Potential Applications

Transition metals are one of the central aspects of modern coordination chemistry research. In addition to being well-studied, cobalt is a unique transition metal due to its presence in vitamin B12. Pyrazole-based structures are common in nature and organic synthesis. Over the past decade, our research group has focused on synthesizing and characterizing novel cobalt, nickel, and copper organometallic complexes. To date, we have reported three cobalt complexes, five nickel complexes and one copper complex with pyrazole-derived ligands. Based on the current scientific data, we are optimistic about potential applications of our coordination complexes with cobalt and pyrazole-based ligands. In this work we review applications of cobalt complexes with pyrazole-based ligands described in recent literature to explore possible applications of compounds synthesized and characterized by our research group.

Silver CVD and ALD Precursors: Synthesis, Properties, and Application in Deposition Processes

This review summarized the developments in the field of volatile silver complexes, which can serve as precursors in gas-transport reactions for the production of thin films and metal nanoparticles via chemical vapor deposition (CVD) and atomic layer deposition (ALD). Silver-based films and nanoparticles are widely used in various high-tech fields, including medicine. For effective use in CVD and ALD processes, the properties of silver precursors must be balanced in terms of volatility, thermal stability, and reactivity. In this review, we focus on the synthesis and comprehensive analysis of structural and thermal characteristics for the most promising classes of volatile silver complexes, as well as organometallic compounds. Following the specifics of silver chemistry, some features of the use of precursors and their selection, as well as several key directions to improving the efficiency of silver material deposition processes, are also discussed.

Ferrocene-Functionalized Atomically Precise Metal Clusters Exhibit Synergistically Enhanced Performance for CO2 Electroreduction.

The integration of organometallic compounds with metal nanoparticles can, in principle, generate hybrid nanocatalysts endowed with augmented functionality, presenting substantial promise for catalytic applications. Herein, we synthesize an atomically precise metal cluster (Ag9Cu6) catalyst integrated with alkynylferrocene molecules (Ag9Cu6-Fc). This hybrid catalyst design facilitates a continuous electron transfer channel via an ethynyl bridge and establishes a distinctive local chemical environment, resulting in remarkably enhanced catalytic activity in CO2 electroreduction. The Ag9Cu6-Fc catalyst achieves a record-high product selectivity of CO Faradaic efficiency of 100% and an industrial-level CO partial current density of -680 mA/cm2, surpassing the performance of the Ag9Cu6 cluster (62% and -230 mA/cm2, respectively) without ferrocene functionalization in a membrane electrode assembly cell. Operando experimental and computational findings offer valuable insights into the role of ferrocene functionalization in synergistically improving the catalytic performance of metal clusters, propelling the advancement of metallic-organometallic hybrid nanoparticles for energy conversion technologies.

Natural Abundance 195Pt-13C Correlation NMR Spectroscopy on Surfaces Enabled by Fast MAS Dynamic Nuclear Polarization

Surface organometallic chemistry has developed as an effective strategy for the rational design and synthesis of well-defined, single-site Pt-based heterogeneous catalysts. Given its high sensitivity to changes in electronic structure, 195Pt solid-state NMR spectroscopy offers a unique approach to investigate the chemical structure and local environment of Pt surface sites, providing invaluable insights for establishing structure-activity relationships. However, this approach is typically hindered by severe sensitivity issues, due to the low loading of Pt sites and the often-encountered large 195Pt chemical shift anisotropies. To overcome this limitation, 195Pt NMR signature of surface metal centers can be indirectly detected through protons. Indirect detection on 13C spins, has also been demonstrated to be feasible by combining isotopic labeling with dynamic nuclear polarization (DNP). Here, we extend this methodology to a supported Pt complex at natural abundance. The material was prepared by grafting (COD)PtMeOSi(OtBu)3 (COD = 1,5-cyclooctadiene, Me = methyl and tBu = tert-butyl) onto partially dehydroxylated silica. DNP enhanced two-dimensional through-bond 13C{195Pt} heteronuclear correlation experiments were successfully implemented at fast magic angle spinning. They enabled the detection of the 0.37% NMR-responsive surface species, thereby showcasing the remarkable sensitivity of this approach and its broad applicability. Key bonding information was obtained by measuring the correlated 13C and 195Pt isotopic chemical shifts as well as 1J(13C-195Pt) coupling constants, confirming directly the coordination structure of the surface Pt sites.

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Recent Advances in Thermally Activated Delayed Fluorescent Materials in Type II Photodynamic Therapy.

Photodynamic therapy (PDT) represents a novel, dual-stage cancer treatment approach that combines light energy and photosensitizers to destroy cancerous and precancerous cells through the generation of radicals (Type I) or singlet oxygen (Type II). Since the early 2010s, PDT has advanced significantly, with the focus shifting toward the exploration of molecules capable of thermally activated delayed fluorescence (TADF) as viable alternatives to traditional metallic complexes and organometallic compounds for producing the necessary active species. TADF molecules exhibit higher energy conversion efficiency, long-lived triplet excitons, tunable photophysical properties, and a small singlet-triplet energy gap, facilitating efficient intersystem crossing and enhanced singlet oxygen generation. As metal-free luminophores, they offer benefits such as reduced health risks, high structural flexibility, and biocompatibility, which can significantly enhance PDT treatment efficacy. Notably, in 2019, a pivotal shift occurred, with researchers concentrating their efforts on identifying and investing in potential molecules specifically for Type II PDT applications. This review presents the innovative use of materials characterized by closely spaced S1 and T1 orbitals, crucial for the efficient generation of singlet oxygen in PDT. Exploring these materials opens new avenues for enhancing the efficacy and specificity of PDT, offering promising for future cancer treatments.

Recent Catalytic Applications of Ferrocene and Ferrocenium Cations in the Syntheses of Organic Compounds

Ferrocene and its oxidized counterpart, the ferrocenium cation, represent a fascinating class of organometallic compounds with broad utility across various fields, including organic synthesis, pharmaceuticals, and materials science. Over the years, ferrocene, ferrocenium cations, and their derivatives have also gained prominence for their versatility in catalytic processes. This review article offers an overview of the research of the last decade into ferrocene- and ferrocenium-based catalysis. Key developments are highlighted in catalytic oxidation, cross-coupling, polymerization reactions, and redox-switchable catalysis, as well as the application of ferrocenium cations as Lewis acid catalysts.

Asparagus: A toolkit for autonomous, user-guided construction of machine-learned potential energy surfaces

With the establishment of machine learning (ML) techniques in the scientific community, the construction of ML potential energy surfaces (ML-PES) has become a standard process in physics and chemistry. So far, improvements in the construction of ML-PES models have been conducted independently, creating an initial hurdle for new users to overcome and complicating the reproducibility of results. Aiming to reduce the bar for the extensive use of ML-PES, we introduce Asparagus, a software package encompassing the different parts into one coherent implementation that allows an autonomous, user-guided construction of ML-PES models. Asparagus combines capabilities of initial data sampling with interfaces to ab initio calculation programs, ML model training, as well as model evaluation and its application within other codes such as ASE or CHARMM. The functionalities of the code are illustrated in different examples, including the dynamics of small molecules, the representation of reactive potentials in organometallic compounds, and atom diffusion on periodic surface structures. The modular framework of Asparagus is designed to allow simple implementations of further ML-related methods and models to provide constant user-friendly access to state-of-the-art ML techniques. Program summaryProgram Title:AsparagusCPC Library link to program files:https://doi.org/10.17632/9w9xw7mp2h.1Developer's repository link:https://github.com/MMunibas/AsparagusLicensing provisions: MITProgramming language: PythonSupplementary material: Access to Documentation at https://asparagus-bundle.readthedocs.ioNature of problem: Constructing machine-learning (ML) based potential energy surfaces (PESs) for atomistic simulations is a multi-step process that requires a broad knowledge in quantum chemistry, nuclear dynamics and programming. So far, efforts mainly focused on developing and improving ML model architectures. However, there was less effort spent on providing tools for consistent and reproducible workflows that support the construction of ML-PES for a variety of chemical systems for the broader science community.Solution method:Asparagus is a program package written in Python that provides a streamlined and extensible workflow with a user-friendly command structure to support the construction of ML-PESs. This is achieved by bundling and linking data generation and sampling techniques, data management, model training, testing and evaluation tools into one modular, comprehensive workflow including interfaces to other simulation packages for the application of the ML-PESs. By lowering the entrance barriers especially for new users, Asparagus supports the generation and adjustment of ML-PESs that allow an increased focus on the physico-chemical evaluation of the chemical system or application in molecular dynamics simulations.Additional comments including restrictions and unusual features:Asparagus is a modular package written in Python providing an underlying structure for further extensions and maintenance. Currently, methods based on message-passing neural network (NN) models using the PyTorch Python package are available. Additions of new models and interfaces to already implemented modules are possible. The NN architecture and hyperparameters are stored in a global configuration module and as a json file for documentation. Except for essential input information, default input parameters are used if not specifically defined otherwise, which allows a quick setup for the construction of a ML-PES but also the fine-tuning for specific needs.

Room-Temperature Formate Ester Transfer Hydrogenation Enables an Electrochemical/Thermal Organometallic Cascade for Methanol Synthesis from CO2.

The reduction of CO2 to synthetic fuels is a valuable strategy for energy storage. However, the formation of energy-dense liquid fuels such as methanol remains rare, particularly under low-temperature and -pressure conditions that can be coupled to renewable electricity sources via electrochemistry. Here, a multicatalyst system pairing an electrocatalyst with a thermal organometallic catalyst is introduced, which enables the reduction of CO2 to methanol at ambient temperature and pressure. The cascade methanol synthesis proceeds via CO2 reduction to formate by electrocatalyst [Cp*Ir(bpy)Cl]+ (Cp* = pentamethylcyclopentadienyl, bpy = 2,2'-bipyridine), Fischer esterification of formate to isopropyl formate catalyzed by trifluoromethanesulfonic acid (HOTf), and thermal transfer hydrogenation of isopropyl formate to methanol facilitated by the organometallic catalyst (H-PNP)Ir(H)3 (H-PNP = HN(C2H4PiPr2)2). The isopropanol solvent plays several crucial roles: activating formate ion as isopropyl formate, donating hydrogen for the reduction of formate ester to methanol via transfer hydrogenation, and lowering the barrier for transfer hydrogenation through hydrogen bonding interactions. In addition to reporting a method for room-temperature reduction of challenging ester substrates, this work provides a prototype for pairing electrochemical and thermal organometallic reactions that will guide the design and development of multicatalyst cascades.

Harnessing Deep Eutectic Solvents for Regioselective Polar Additions toα,βUnsaturatedKetones and Aldehydes.

Advancing the use of air-sensitive polar organometallic Grignard and organolithium reagents under more environmentally benign conditions, here we report the addition of these reagents toa-bunsaturated ketones and aldehydes using the deep eutetic solvent (DES) choline chloride (ChCl): glycerol (Gly) (1:2), under air. Reactions occur at room temperature within seconds with excellent regioselective control. Furthering understanding of how these C-C bond forming processes take place in these reaction media,we have explored the surface concentration of the organic substrate (chalcone) in DES using interfacial tension and neutron reflectivity measurements, finding that chalcone is concentrated at the DES-hydrocarbon interface compared to the bulk concentration, although the interfacial chalcone concentration is still relatively low in this system. The influence of aggregation of the organometallic reagent in the organic solvent employed has also been evaluated, revealing the importance of achieving a balance between activation (via de-aggregation) and stability (to avoid its decomposition in the DES). This DES approach has been successfully extended to double additions toa-bunsaturated estes and for one pot sequential 1,4 and 1,2 additions to ketones, providing a new entry point to a range of tertiary-alcohols, minimising the use of organic solvents and avoiding intermediate time-consuming purification steps.

Synthesis, Photophysical Properties and Optical Limiting Behavior of Organometallic Complexes: Influence of Metal Centers and Conjugated Diimine Ligands

AbstractFour organometallic complexes featuring identical conjugated diimine ligands and varying transition metal centers (Rh(III), Ir(III), Ru(II), and Os(II)) were synthesized. A comprehensive investigation of the photophysical properties of these complexes and their corresponding diimine ligands was conducted by UV‐vis absorption, emission, and transient absorption (TA) spectroscopy, as well as optical power limiting (OPL) measurements. The incorporation of fluorene components with alkyl chains enhanced the π‐conjugation of the ligand, prevented intermolecular π‐π stacking, and improved complex solubility. The diimine ligands showed a slight solvation effect in their emission spectra, indicating that the main property of their emissive state was intramolecular charge transfer (CT). According to the valence states of the four complexes, they can be divided into two classes (Rh(III), Ir(III)) and (Ru(II), Os(II)). For TA spectrum, the former group exhibited positive ΔOD values across the 400~800 nm range, while the latter showed large inverted peaks at 420~500 nm due to significant ground‐state absorption in this wavelength range. Additionally, the optical limiting conduct of the complexes observed the order: 1 d>1 a>1 c>1 b. Complex 1 d exhibits powerful reverse saturable absorption (RSA) properties at 532 nm and could probably be used as an wonderful nonlinear absorbing material.

Spin Crossover and Its Application in Organometallic Catalysis: Concepts and Recent Progress.

Spin crossover is one of the most important properties of open-shell metal complexes. In organometallic catalytic reactions, catalysts can alter reaction kinetics by spin crossover, i. e., accelerating or hindering the reaction progression, as well as altering reaction pathways, modulating the reaction selectivity or promoting new reactions. This personal account outlines the introduction and development of important concepts such as "two-state reactivity" involving spin crossover, and proposes a new concept, "spin-responsive catalysis" to summarize the catalytic processes in which spin effects are present. Finally, the electronic mechanism of spin crossover accelerating the reaction and the role of spin crossover in changing the reaction path and regulating the reaction selectivity are introduced by taking two recent typical iron-catalyzed reactions recently reported by our group as examples.

Friedel–Crafts Reactivity with Sulfondiimidoyl Fluorides for the Synthesis of Heteroaryl Sulfondiimines

AbstractSulfur functional groups are ubiquitous in molecules used in the pharmaceutical and agrochemical industries, and within these collections sulfones hold a prominent position. The double aza‐analogues of sulfones, sulfondiimines, offer significant potential in discovery chemistry but to date their applications have been limited by the lack of convenient synthetic routes. The existing methods mainly rely on imination of low‐valent‐sulfur intermediates, or the combination of pre‐formed organometallic reagents and electrophilic S(VI)‐functionalities. Herein, we describe a Friedel–Crafts‐type reaction of sulfondiimidoyl fluorides with (hetero)aryls. This new SuFEx reactivity benefits from broad functional group tolerance, mild reaction conditions, and does not require the use of pre‐formed organometallic reagents. The efficient use of unprotected indoles and pyrroles, as well as furan, thiophene and carbocyclic aromatics, further demonstrates the advantages of these reactions. We show that the reactivity of the sulfondiimidoyl fluorides can be tuned by switching the N‐substituents, allowing an expansion of the range of coupling partners. The utility of the transformation is exemplified by the synthesis of the sulfondiimine analogue of the HIV‐I reverse transcriptase‐inhibitor L‐737,126.

Nanometer-thick TiO2 channel thin film transistors as radical monitors for plasma enhanced atomic layer deposition

Nanometer-thick-TiO2-channel thin-film transistors (TFTs) are examined as oxidizing-agent monitors for room-temperature atomic layer deposition (RTALD). RTALD is a plasma-based process using plasma-excited humidified argon where OH radicals oxidize the precursor-gas adsorbed surface. In the TFT, the anatase TiO2 channel, with a thickness of 16 nm, is attached to a 300 nm thick gate capacitor of SiO2, while the channel surface is exposed to the ALD ambient. A heavily doped n-type Si substrate attached to the gate SiO2 is used as the gate electrode. The gate width and length are 1000 and 60 μm, respectively. When the TFT is installed in the RTALD chamber, the drain-current waveform is recorded in the course of the metal organic gas adsorption, evacuation of the residual gas, oxidization, and evacuation. In the present study, three kinds of metal organic (MO) precursors, tetrakis(dimethyl)amino titanium, tris(dimethyl)amino silane, and trimethyl aluminum are examined. The drain current exhibits strong responses upon the exposure of the plasma excited humidified argon. This suggests that OH radicals in the plasma might oxidize the adsorbed MO precursors to produce the OH moieties, where the surface polarization of OH moieties might enhance channel conductivity. The experimental results suggest the applicability of the present TFT as a plasma monitor in RTALD.

Friedel-Crafts Reactivity with Sulfondiimidoyl Fluorides for the Synthesis of Heteroaryl Sulfondiimines.

Sulfur functional groups are ubiquitous in molecules used in the pharmaceutical and agrochemical industries, and within these collections sulfones hold a prominent position. The double aza-analogues of sulfones, sulfondiimines, offer significant potential in discovery chemistry but to date their applications have been limited by the lack of convenient synthetic routes. The existing methods mainly rely on imination of low-valent-sulfur intermediates, or the combination of pre-formed organometallic reagents and electrophilic S(VI)-functionalities. Herein, we describe a Friedel-Crafts-type reaction of sulfondiimidoyl fluorides with (hetero)aryls. This new SuFEx reactivity benefits from broad functional group tolerance, mild reaction conditions, and does not require the use of pre-formed organometallic reagents. The efficient use of unprotected indoles and pyrroles, as well as furan, thiophene and carbocyclic aromatics, further demonstrates the advantages of these reactions. We show that the reactivity of the sulfondiimidoyl fluorides can be tuned by switching the N-substituents, allowing an expansion of the range of coupling partners. The utility of the transformation is exemplified by the synthesis of the sulfondiimine analogue of the HIV-I reverse transcriptase-inhibitor L-737,126.

Reversible Grafting in Surface Organometallic Chemistry with a Late Transition‐Metal Amidinate Precursor

AbstractSupported catalysts are central to industrial catalytic processes. While traditional synthesis methods often yield poorly defined materials, thus complicating structural elucidation, Surface Organometallic Chemistry (SOMC) offers a solution, producing well‐defined structures. Recent advances in SOMC precursor development have shown that amidinate‐based complexes are a privileged class of precursors to generate supported metallic nanoparticles. In that context, this study investigates the grafting mechanism of a prototypical amidinate precursor, Ir(COD)(DIA) (1‐Ir), onto SiO2. Unique to amidinate complexes, grafting is shown to occur without ligand release, creating a reversible covalent bond. Using tris(tert‐butoxy)silanol as a molecular analogue for a silanol group on SiO2, the structure of the grafted species is elucidated by single X‐Ray diffraction, comparison of IR spectroscopy, and X‐Ray absorption spectroscopy (XAS) data. The reversibility of the reaction with O−H groups is demonstrated using variable‐temperature NMR spectroscopy, IR spectroscopy, and is supported by DFT calculations. Notably, we show that a partial degrafting is also possible at elevated temperatures under vacuum.

Versatile Organometallic Synthesis of 0D/2D Metal@Germanane Nanoarchitectonics for Electrochemical Energy Conversion Applications.

Hydrogen-terminated 2D-Germanane (2D-GeH), a germanium-based 2D material akin to graphene, is receiving enormous attention owing to its predicted optoelectronic characteristics. However, experimental research of 2D-GeH is still in an early stage, and therefore its real implementation for task-specific applications will depend on the correct development of suitable chemical functionalization methods. Herein, a general and straightforward organometallic (OM) approach is provided for the robust functionalization of 2D-GeH with different 0D noble metal nanoparticles (M-NPs), resulting in 0D/2D M@GeH nanoarchitectonics. As a proof-of-principle, 0D/2D Pt@GeH and Au@GeH nanoarchitectonics have been successfully synthesized, characterized, and explored as unconventional electrocatalysts for boosting energy conversion reactions. While the hydrogen evolution reaction activity was evaluated for Pt@GeH, the oxygen reduction reaction was interrogated for Au@GeH. Interestingly, the implanted catalytic features of M-NPs yielded to 0D/2D M@GeH nanoarchitectonics with enhanced energy conversion activity comparing to pristine 2D-GeH counterpart. This work proves the suitability of 2D-GeH as unconventional substrates to stabilize nobleM-NPs, and the versatility of the OM approach for the custom design of a new family of 0D/2D M@GeH nanoarchitectonics to expand the implementation of monoelemental 2D materials as promising electrocatalysts in energy conversion field and beyond.

Amide Synthesis from Decarboxylative Coupling of Isocyanates and Carboxylic Acids.

Isocyanates are versatile electrophiles that can react with a wide range of nucleophiles to afford important organic structures. Although the reactions between isocyanates and alcohols, amines and organometallic reagents have been well established, the synthesis of amides through the decarboxylative condensation of carboxylic acids and isocyanates is less appreciated. In this review, the synthesis of isocyanates and its application on amide synthesis through the condensation with carboxylic acids are summarized and discussed. It is our hope that this review will attract more attention to this less mentioned transformation and inspire new developments in the fields of organic synthesis, polymer synthesis and chemical biology.

Biomarkers of Nicotine and Toxicant Exposure by E-liquid Nicotine Concentration Level among U.S. Adult Exclusive E-cigarette Users.

The current e-cigarette market has been rapidly evolving with an increase in the share of high nicotine concentration vaping products. This study examined urinary biomarkers of exposure (BOEs) by nicotine concentration level among exclusive e-cigarette users. Data were drawn from Wave 5 (December 2018-November 2019) of the Population Assessment of Tobacco and Health (PATH) Study. Between-subject differences in BOEs of nicotine, metal, tobacco-specific nitrosamine (TSNA), and volatile organic compounds (VOC) were examined across e-cigarettes containing nicotine or not (yes [n=300] vs. no [n=31] vs. non-tobacco use [n=3021]) and different nicotine concentration levels (0.1-1.7%, 1.8-4.9%, and 5.0%+). Among 3353 participants, exclusive e-cigarette users exhibited higher mean concentrations of nicotine metabolites than non-tobacco users. Nicotine e-cigarette users had higher concentrations of TNE2 (mean [95% CI]=21.8 [15.2-31.2] vs. 0.2 [0.1-0.6] nmol/mg creatinine, p<.0001) and cotinine (1418.2 [998.0-2015.4] vs. 12.2 [0.1-0.6], p<.0001) ng/mg creatinine, p<.0001) than non-nicotine e-cigarette users. Users of e-cigarette products with nicotine levels of 1.8-4.9% had higher TNE2 and cotinine levels than those using 0.1-1.7%, though differences were insignificant after adjusting for covariates. As compared to non-tobacco users, nicotine vapers had higher concentrations of lead (adjusted p=0.01). Nicotine containing e-cigarette users exhibited elevated levels of nicotine metabolites than non-nicotine containing vapers and non-tobacco users. Future research needs to investigate health effects of e-cigarette use across different nicotine levels Impact: Regulating the nicotine content in e-cigarettes could be crucial in managing nicotine exposure and potentially mitigating associated health risks.