Comparison of the structural, electrochemical, and spectroscopic properties of two cryptates of trivalent uranium.

We describe a study of the influence of cryptand denticity on the structural, electronic, and electrochemical properties of UIII-containing cryptates. Two cryptands (2.2.2 and 2.2.1) are reported. The cryptand with the smaller denticity leads to negative electrochemical potentials and shorter bond lengths that are consistent with a better fit for UIII than the larger cryptand. These studies provide insight into the rational design of cryptand-based ligands for trivalent uranium.

Expanding the Coordination of f-Block Metals with Tris[2-(2-methoxyethoxy)ethyl]amine: From Molecular Complexes to Cage-like Structures.

Low-valent f-block metals have intrinsic luminescence, electrochemical, and magnetic properties that are modulated with ligands, causing the coordination chemistry of these metals to be imperative to generating critical insights needed to impact modern applications. To this end, we synthesized and characterized a series of twenty-seven complexes of f-metal ions including EuII, YbII, SmII, and UIII and hexanuclear clusters of LaIII and CeIII to study the impact of tris[2-(2-methoxyethoxy)ethyl]amine, a flexible acyclic analogue of the extensively studied 2.2.2-cryptand, on the coordination chemistry and photophysical properties of low-valent f-block metals. We demonstrate that the flexibility of the ligand enables luminescence tunability over a greater range than analogous cryptates of EuII in solution. Furthermore, the ligand also displays a variety of binding modes to f-block metals in the solid state that are inaccessible to cryptates of low-valent f-block metals. In addition to serving as a ligand for f-block metals of various sizes and oxidation states, tris[2-(2-methoxyethoxy)ethyl]amine also deprotonates water molecules coordinated to trivalent triflate salts of f-block metal ions, enabling the isolation of hexanuclear clusters containing either LaIII or CeIII. The ligand was also found to bind more tightly to YbII and UIII in the solid state compared to 2.2.2-cryptand, suggesting that it can play a role in the isolation of other low-valent f-block metals such CfII, NpIII, and PuIII. We expect that our findings will inspire applications of tris[2-(2-methoxyethoxy)ethyl]amine in the design of light-emitting diodes and the synthesis of extremely reducing divalent f-block metal complexes that are of interest for a wide range of applications.

Combining [MoVIO3] and [M0(CO)3] (M = Mo, Cr) Fragments within the Same Complex: Synthesis and Reactivity of the Single Oxo-Bridged Heterobimetallics Supported by Xanthene-Based Heterodinucleating Ligands.

A functional model of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme requires the presence of an oxidant (metal-oxo) and a metal-bound carbonyl in close proximity. In this work, we report the synthesis, characterization, and reactivity of a heterobimetallic complex combining Mo(VI) trioxo with Mo(0) tricarbonyl. The formation of the heterobimetallic complex is facilitated by the xanthene-bridged heterodinucleating ligand containing a hard catecholate chelate and a soft iminopyridine chelate. A catechol-coordinated square-pyramidal [MoVIO3] fragment interacts directly with the iminopyridine-bound [Mo0(CO)3] fragment via a single (oxo) bridge, with the overall disposition being related to the proposed first step in the CODH mechanism, where square-pyramidal [MoVIO2S] interacts with the [Cu-CO] via a single sulfido bridge. Our attempt to obtain a sulfido-bridged analogue (using [MoO3S]2- precursor) led to a mixture of products possibly containing different (oxo and sulfido) bridges. Despite a direct interaction between Mo(VI) and Mo(0) segments, no internal redox is observed, with the high lying occupied MOs being mostly d-π orbitals at Mo0(CO)3 and the low lying unoccupied MOs being d-π orbitals at MoVIO3. Due to the overall rigid structure, the heterobimetallic complex was found to be stable up to 100 °C in DMF-d7 (based on 1H NMR). The decomposition of the complex above this temperature does not produce CO2 (based on gas chromatography), dissociating stable Mo(CO)3(DMF)3 instead (based on IR). We also synthesized and studied the reactivity of the Mo(VI)/Cr(0) analogue. While this complex demonstrated more facile decomposition, no CO2 production was observed. Density functional theory calculations suggest that the formation of [CO2]2- and its subsequent reductive elimination is endergonic in the present system, likely due to the stability of fac-Mo0(CO)3 and the relative nucleophilic character of the carbonyl carbon engendered by back donation from Mo(0). The calculations also indicate that the replacement of one oxo by sulfido (both terminal and bridging), replacement of catechol with dithiolene, and replacement of Mo(0) with Cr(0) does not affect significantly the energetics of the process, likely requiring the use a less stable and less π-basic CO anchor.

Thermal atomic layer deposition of Er2O3 films from a volatile, thermally stable enaminolate precursor.

Thin films of Er2O3 films were grown by atomic layer deposition using the Er precursor tris(1-(dimethylamino)-3,3-dimethylbut-1-en-2-olate)erbium(III) (Er(L1)3), with water as the co-reactant. Saturative, self-limited growth was observed at a substrate temperature of 200 °C for pulse lengths of ≥4.0 s for Er(L1)3 and ≥0.2 s for water. An ALD window was observed from 175 to 225 °C with a growth rate of about 0.25 Å per cycle. Er2O3 films grown at 200 °C on Si(100) and SiO2 substrates with a thickness of 33 nm had root mean square surface roughnesses of 1.75 and 0.75 nm, respectively. Grazing incidence X-ray diffraction patterns showed that the films were composed of polycrystalline Er2O3 at all deposition temperatures on Si(100) and SiO2 substrates. X-ray photoelectron spectroscopy revealed stoichiometric Er2O3, with carbon and nitrogen levels below the detection limits after argon ion sputtering to remove surface impurities. Transmission electron microscopy studies of Er2O3 film growth in nanoscale trenches (aspect ratio = 10) demonstrated conformal coverage.

A review of electrophoretic separations in temperature-responsive Pluronic thermal gels.

Gel electrophoresis is a ubiquitous bioanalytical technique used in research laboratories to validate protein and nucleic acid samples. Polyacrylamide and agarose have been the gold standard gel materials for decades, but an alternative class of polymer has emerged with potentially superior performance. Pluronic thermal gels are water-soluble polymers that possess the unique ability to undergo a change in viscosity in response to changing temperature. Thermal gels can reversibly convert between low-viscosity liquids and high-viscosity solid gels using temperature as an adjustable parameter. The properties of thermal gels provide unmatched flexibility as a dynamic separations matrix to measure analytes ranging from small molecules to cells. This review article describes the physical and chemical properties of Pluronic thermal gels to provide a fundamental overview of polymer behavior. The performance of thermal gels is then reviewed to highlight their applications as a gel matrix for electrokinetic separations in capillary, microfluidic, and slab gel formats. The use of dynamic temperature-responsive gels in bioanalytical separations is an underexplored area of research but one that holds exciting potential to achieve performance unattainable with conventional static polymers.

Simple magnesium alkoxides: synthesis, molecular structure, and catalytic behaviour in the ring-opening polymerization of lactide and macrolactones and in the copolymerization of maleic anhydride and propylene oxide.

The synthesis of two chiral bulky alkoxide pro-ligands, 1-adamantyl-tert-butylphenylmethanol HOCAdtBuPh and 1-adamantylmethylphenylmethanol HOCAdMePh, is reported and their coordination chemistry with magnesium(II) is described and compared with the coordination chemistry of the previously reported achiral bulky alkoxide pro-ligand HOCtBu2Ph. Treatment of n-butyl-sec-butylmagnesium with two equivalents of the racemic mixture of HOCAdtBuPh led selectively to the formation of the mononuclear bis(alkoxide) complex Mg(OCAdtBuPh)2(THF)2. 1H NMR spectroscopy and X-ray crystallography suggested the selective formation of the C2-symmetric homochiral diastereomer Mg(OCRAdtBuPh)2(THF)2/Mg(OCSAdtBuPh)2(THF)2. In contrast, the less sterically encumbered HOCAdMePh led to the formation of dinuclear products indicating only partial alkyl group substitution. The mononuclear Mg(OCAdtBuPh)2(THF)2 complex was tested as a catalyst in different reactions for the synthesis of polyesters. In the ROP of lactide, Mg(OCAdtBuPh)2(THF)2 demonstrated very high activity, higher than that shown by Mg(OCtBu2Ph)2(THF)2, although with moderate control degrees. Both Mg(OCAdtBuPh)2(THF)2 and Mg(OCtBu2Ph)2(THF)2 were found to be very effective in the polymerization of macrolactones such as ω-pentadecalactone (PDL) and ω-6-hexadecenlactone (HDL) also under mild reaction conditions that are generally prohibitive for these substrates. The same catalysts demonstrated efficient ring-opening copolymerization (ROCOP) of propylene oxide (PO) and maleic anhydride (MA) to produce poly(propylene maleate).

Studies Relevant to the Functional Model of Mo-Cu CODH: In Situ Reactions of Cu(I)-L Complexes with Mo(VI) and Synthesis of Stable Structurally Characterized Heterotetranuclear MoVI2CuI2 Complex.

In this study, we report the synthesis, characterization, and reactions of Cu(I) complexes of the general form Cu(L)(LigH2) (LigH2 = xanthene-based heterodinucleating ligand (E)-3-(((5-(bis(pyridin-2-ylmethyl)amino)-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)imino)methyl)benzene-1,2-diol); L = PMe3, PPh3, CN(2,6-Me2C6H3)). New complexes [Cu(PMe3)(LigH2)] and [CuCN(2,6-Me2C6H3)(LigH2)] were synthesized by treating [Cu(LigH2)](PF6) with trimethylphosphine and 2,6-dimethylphenyl isocyanide, respectively. These complexes were characterized by multinuclear NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry (HRMS), and X-ray crystallography. In contrast, attempted reactions of [Cu(LigH2)](PF6) with cyanide or styrene failed to produce isolable crystalline products. Next, the reactivity of these and previously synthesized Cu(I) phosphine and isocyanide complexes with molybdate was interrogated. IR (for isocyanide) and 31P NMR (for PPh3/PMe3) spectroscopy demonstrates the lack of oxidation reactivity. We also describe herein the first example of a structurally characterized multinuclear complex combining both Mo(VI) and Cu(I) metal ions within the same system. The heterobimetallic tetranuclear complex [Cu2Mo2O4(µ2-O)(Lig)2]·HOSiPh3 was obtained by the reaction of the silylated Mo(VI) precursor (Et4N)(MoO3(OSiPh3)) with LigH2, followed by the addition of [Cu(NCMe)4](PF6). This complex was characterized by NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallography.

Toward quantification of hypoxia using fluorinated EuII/III-containing ratiometric probes.

Hypoxia is a prognostic biomarker of rapidly growing cancers, where the extent of hypoxia is an indication of tumor progression and prognosis; therefore, hypoxia is also used for staging while performing chemo- and radiotherapeutics for cancer. Contrast-enhanced MRI using EuII-based contrast agents is a noninvasive method that can be used to map hypoxic tumors, but quantification of hypoxia using these agents is challenging due to the dependence of signal on the concentration of both oxygen and EuII. Here, we report a ratiometric method to eliminate concentration dependence of contrast enhancement of hypoxia using fluorinated EuII/III-containing probes. We studied three different EuII/III couples of complexes containing 4, 12, or 24 fluorine atoms to balance fluorine signal-to-noise ratio with aqueous solubility. The ratio between the longitudinal relaxation time (T1) and 19F signal of solutions containing different ratios of EuII- and EuIII-containing complexes was plotted against the percentage of EuII-containing complexes in solution. We denote the slope of the resulting curves as hypoxia indices because they can be used to quantify signal enhancement from Eu, that is related to oxygen concentration, without knowledge of the absolute concentration of Eu. This mapping of hypoxia was demonstrated in vivo in an orthotopic syngeneic tumor model. Our studies significantly contribute toward improving the ability to radiographically map and quantify hypoxia in real time, which is critical to the study of cancer and a wide range of diseases.

"Catch-Store-Release" Strategy for the Stabilization of 4,4'-Methylene Diphenyl Diisocyanate (4,4'-MDI).

4,4'-Methylene diphenyl diisocyanate (MDI) is an industrially crucial compound, being one of the most utilized linkers in the polyurethane industry. However, its long-term stability is limited due to dimerization to form insoluble uretdione. Herein we demonstrate an organometallic "catch-store-release" concept aiming at improving the long-term chemical stability of MDI. Treatment of MDI with two equivalents of selected N-heterocyclic carbenes (NHC) forms stable MDI-NHC adducts. Treatment of the adducts with CuCl forms metastable di-CuI complexes that undergo decomposition to re-form MDI (up to 85 %), along with Cu-NHC complexes. The yield of re-formed MDI can be improved (up to 95 %) by the release of the NHC ligands in the form of thiourea; this prevents subsequent MDI dimerization/polymerization by the carbenes. Furthermore, the need to separate MDI from the reaction mixture can be eliminated by the direct reaction of MDI-NHC complexes with alcohols (as models for diols), that form dicarbamate (as a model for polyurethane) quantitatively.

Properties of Amine-Containing Ligands That Are Necessary for Visible-Light-Promoted Catalysis with Divalent Europium.

We describe a study of the influence of amine-containing ligands on the photoredox-relevant properties of EuII toward the rational design of EuII-containing catalysts for visible-light-promoted photoredox reactions. We report our observations of the effects of the degree of functionalization of amines, denticity, and macrocylic ligands on the absorbance of EuII. Ligands that contain secondary amines bathochromically shift the absorbance of EuCl2 relative to ligands that contain primary or tertiary amines. Similarly, ligands of larger denticity have a larger bathochromic shift of the absorbance than ligands of smaller denticity. We observed that macrocyclic ligands have a larger effect on the absorbance of EuCl2 than nonmacrocyclic ligands. Also, we report the photoredox reactivity of four new EuII-containing complexes. These observations are potentially influential in understanding the ligand properties that promote the use of EuII in visible-light-promoted photoredox catalysis.

Development of a Highly Selective Ni(II) Chelator in Aqueous Solution.

The design, synthesis, and characterization of a novel Ni(II) chelator SG-20 is reported. SG-20 is selective in binding to Ni(II) versus other metal ions including Cu(II), Fe(II), Co(II), and Zn(II). At pH = 7.1, SG-20 binds Ni(II) with a Kd = 7.0 ± 0.4 µM. Job analysis indicates that SG-20 binds to both Ni(II) and Cu(II) with a 1:1 stoichiometry. Affinity of SG-20 for Ni(II) is pH dependent and decreases upon lowering to pH 4.0. A green solid was isolated from the reaction of SG-20 with NiCl2·6H2O in MeOH and characterized by X-ray photoelectron spectroscopy (XPS), electronic absorption and infrared (IR) spectroscopies, and mass spectrometry. Collectively, XPS and IR analysis revealed Ni-N and Ni-O interactions and a shift in C-O asymmetric and symmetric stretches consistent with Ni binding. Attempts to crystalize a mononuclear complex were unsuccessful, likely due to the Ni-SG-20 complex being in equilibrium with higher order species in solution. However, reaction of SG-20 with NiCl2·6H2O in water followed by slow evaporation yielded green crystals that were characterized by electronic absorption spectroscopy (λmax = 260 nm) and X-ray crystallography. These analyses revealed that SG-20 supports formation of a complex cluster containing six SG-20 ligands, 15 Ni(II), and three Na(I) centers, with two distinct types of Ni atoms in its outer and inner core. The nine Ni atoms present in the inner core were bound by oxo and carbonate bridges, whereas the six Ni atoms present in its outer shell were bound to N, O, and S donor atoms derived from SG-20. Overall, X-ray crystallographic analysis revealed that two chelator arms of SG-20 bind to one Ni(II) ion with an axial aqua ligand, whereas the third arm is free to interact with Ni ions within the central cluster, supporting the goal of Ni capture.

Solid-state and solution-phase characterization of SmII-aza[2.2.2]cryptate and its methylated analogue.

Two new SmII-azacryptates are reported that differ in steric hindrance and Lewis basicity of donor atoms. The sterically hindered complex has a smaller coordination number and a more negative electrochemical potential than the complex with less steric hindrance.

Identification of seven-coordinate LnIII ions in a LnIII[15-MCFe III N(shi)-5](OAc)2Cl species crystallized from methanol and pyridine.

The title metallacrown (MC) complexes LnIII[15-MCFeIIIN(shi)-5](OAc)2CI(C5H5N)6 (Ln1), where OAc- is acetate, shi3- is salicylhydroximate, and Ln = Gd and Dy, were synthesized via a self-assembly reaction in methanol and pyridine. Single crystals were grown using slow evaporation and characterized using X-ray diffraction. Seven-coordinate capped octahedron geometries were observed for the lanthanide ion in both complexes, which is uncommon for trivalent lanthanide species. The 15-MC-5 is a ruffled metallacrown archetype similar to previously reported mixed-valent manganese metallacrowns.

Near-Infrared Lanthanide-Based Emission from Fused Bis[Ln(III)/Zn(II) 14-metallacrown-5] Coordination Compounds.

A set of (Ln[14-MCZn(II)N(quinHA)-5])2Ln2Zn2(quinHA)2(ph)2(Hph)4(OH)8(H2O)4 metallacrowns (Ln-1, Ln = Tb, Gd, or Yb; H2quinHA = quinaldic hydroxamic acid, H2ph = phthalic acid) have been synthesized via solution-state self-assembly. The metallacrowns possess an uncommon topology within the metallacrown family where two rarely seen 14-metallacrown-5 moieties are fused by a Yb2Zn2(quinHA)2 bridge. Moreover, Yb-1 analyzed in the solid state exhibits a characteristic near-infrared luminescence signal arising from Yb3+ 2F5/2→2F7/2 transition despite the proximity of high energy O-H oscillators.

Synthesis and structure of a new bulky bis-(alkoxide) ligand on a terphenyl platform.

A new sterically bulky chelating bis-(alkoxide) ligand 3,3'-([1,1':4',1''-terphen-yl]-2,2''-di-yl)bis-(2,2,4,4-tetra-methyl-pentan-3-ol), (H2[OO]tBu), was prepared in a two-step process as the di-chloro-methane monosolvate, C36H50O2·CH2Cl2. The first step is a Suzuki-Miyaura coupling reaction between 2-bromo-phenyl-boronic acid and 1,4-di-iodo-benzene. The resulting 2,2''-di-bromo-1,1':4',1''-terphenyl was reacted with t BuLi and hexa-methyl-acetone to obtain the desired product. The crystal structure of H2[OO]tBu revealed an anti conformation of the [CPh2(OH)] fragments relative to the central phenyl. Furthermore, the hydroxyl groups point away from each other. Likely because of this anti-anti conformation, the attempts to synthesize first-row transition-metal complexes with H2[OO]tBu were not successful.

Hexa-µ-acetato-chlorido-(µ-N,2-dioxodo-benzene-1-carboximidato)-µ3-oxido-tetra-iron(III)-water (1/1) and hexa-µ-acetato-(µ-N,2-dioxodo-benzene-1-carboximidato)fluorido-µ3-oxido-tri-pyridine-tetra-iron(III)-pyridine-water (1/1/0.24).

The title compounds, [Fe4(C2H3O2)6(C7H4O3)FO(C5H5N)3]·C5H5N·0.24H2O (1-F) and [Fe4(C2H3O2)6(C7H4O3)ClO(C5H5N)3]·H2O (1-Cl) were synthesized using a self-assembly reaction in methanol and pyridine with stoichiometric addition of salicyl-hydroxamic acid (H3shi), acetic acid (HOAc), and the appropriate ferric halide salt. The compounds crystallize as solvates, where 1-F has one pyridine mol-ecule that is disordered about a twofold axis and one water mol-ecule with an occupancy of 0.24 (2); and 1-Cl has one water mol-ecule that is disordered over two sites with occupancies of 0.71 (1) and 0.29 (1). The space groups for each analog differ as 1-F crystallizes in Fdd2 while 1-Cl crystallizes in P21. The difference in packing is due to changes in the inter-molecular inter-actions involving the different halides. The two mol-ecules are mostly isostructural, differing only by the torsion of the pyrine ligands and slight orientation changes in the acetate ligands. All of the iron(III) ions are in six-coordinate octa-hedral ligand field geometries but each one exhibits a unique coordination environment with various numbers of O (four to six) and N (nought to two) atom donors. Bond-valence sums confirm each iron is trivalent. The hydroximate ligand is bound to three iron(III) ions using a fused chelate motif similar to those in metallacrown compounds.

Synthesis and Cu(I)/Mo(VI) Reactivity of a Bifunctional Heterodinucleating Ligand on a Xanthene Platform.

In an effort to probe the feasibility of a model of Mo-Cu CODH (CODH = carbon monoxide dehydrogenase) lacking a bridging sulfido group, the new heterodinucleating ligand LH2 was designed and its Cu(I)/Mo(VI) reactivity was investigated. LH2 ((E)-3-(((5-(bis(pyridin-2-ylmethyl)amino)-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)imino)methyl)benzene-1,2-diol) features two different chelating positions bridged by a xanthene linker: bis(pyridyl)amine for Cu(I) and catecholate for Mo(VI). LH2 was synthesized via the initial protection of one of the amine positions, followed by two consecutive alkylations of the second position, deprotection, and condensation to attach the catechol functionality. LH2 was found to exhibit dynamic cooperativity between two reactive sites mediated by H-bonding of the catechol protons. In the free ligand, catechol protons exhibit H-bonding with imine (intramolecular) and with pyridine (intermolecular in the solid state). The reaction of LH2 with [Cu(NCMe)4]+ led to the tetradentate coordination of Cu(I) via all nitrogen donors of the ligand, including the imine. Cu(I) complexes were characterized by multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), X-ray crystallography, and DFT calculations. Cu(I) coordination to the imine disrupted H-bonding and caused rotation away from the catechol arm. The reaction of the Cu(I) complex [Cu(LH2)]+ with a variety of monodentate ligands X (PPh3, Cl-, SCN-, CN-) released the metal from coordination to the imine, thereby restoring imine H-bonding with the catechol proton. The second catechol proton engages in H-bonding with Cu-X (X = Cl, CN, SCN), which can be intermolecular (XRD) or intramolecular (DFT). The reaction of LH2 with molybdate [MoO4]2- led to incorporation of [MoVIO3] at the catecholate position, producing [MoO3(L)]2-. Similarly, the reaction of [Cu(LH2)]+ with [MoO4]2- formed the heterodinuclear complex [CuMoO3(L)]-. Both complexes were characterized by multinuclear NMR, UV-vis, and HRMS. HRMS in both cases confirmed the constitution of the complexes, containing molecular ions with the expected isotopic distribution.

Synthesis, characterization, and alkoxide transfer reactivity of dimeric Tl2(OR)2 complexes.

Reaction of LiOCtBu2Ph with TlPF6 forms the dimeric Tl2(OCtBu2Ph)2 complex, a rare example of a homoleptic thallium alkoxide complex demonstrating formally two-coordinate metal centers. Characterization of Tl2(OCtBu2Ph)2 by 1H and 13C NMR spectroscopy and X-ray crystallography reveals the presence of two isomers differing by the mutual conformation of the alkoxide ligands, and by the planarity of the central Tl-O-Tl-O plane. Tl2(OCtBu2Ph)2 serves as a convenient precursor to the formation of old and new [M(OCtBu2Ph)n] complexes (M = Cr, Fe, Cu, Zn), including a rare example of T-shaped Zn(OCtBu2Ph)2(THF) complex, which could not be previously synthesized using more conventional LiOR/HOR precursors. The reaction of [Ru(cymene)Cl2]2 with Tl2(OCtBu2Ph)2 results in the formation of a ruthenium(ii) alkoxide complex. For ruthenium, the initial coordination of the alkoxide triggers C-H activation at the ortho-H of [OCtBu2Ph] which results in its bidentate coordination. In addition to Tl2(OCtBu2Ph)2, related Tl2(OCtBu2(3,5-Me2C6H3))2 was also synthesized, characterized, and shown to exhibit similar reactivity with iron and ruthenium precursors. Synthetic, structural, and spectroscopic characterizations are presented.

Magnetic resonance thermometry using a GdIII-based contrast agent.

The complexes described here serve as contrast agents for magnetic resonance imaging thermometry. The complexes differentially enhance contrast between 275 and 325 K. The basis of the temperature response of the fluorinated contrast complex is the modulation of water exchange caused by trifluoromethyl groups that can be chemically controlled.

Influence of microfabrication on digital PCR performance in bead-based microwell array assays.

Digital PCR (dPCR) is a highly sensitive analytical technique used to quantify DNA targets. Detection sensitivity can be further enhanced by capturing target sequences onto beads for preconcentration and sample cleanup prior to analysis in microfluidic microwell arrays. However, robust digital analysis requires individual beads to be interrogated within individual wells. Fabricating microwells with dimensions ≤ 3 µm is challenging, and the high surface area-to-volume ratio of the wells leaves PCR susceptible to inhibition stemming from materials used during device processing. This report describes the development of a microfabrication procedure to create ultralow-volume wells (100 fL) for bead-based dPCR and characterize the effects of microprocessing materials on assay performance. Standard microfabrication protocols used for creating microelectronics resulted in devices with nanoscopic debris originating from photoresists used during processing. A model dPCR assay was developed to characterize the effects of this debris, which revealed variable PCR inhibition. Debris within microwells attenuated digital and analog assay signals to a greater extent than debris on the device surface. Spatial heterogeneity of debris across devices was quantified to characterize regional PCR inhibition and intra- and inter-device variability. Ultimately, a fabrication procedure was developed to create pristine microfluidic arrays using dual processes to remove positive resist and forgoing use of negative resist entirely, which enabled robust amplification with digital signals matching theoretical predictions. Results from this work catalog the unique performance artifacts from device microfabrication and provide a guide for future studies seeking to conduct robust, high-sensitivity bead-based dPCR assays. Graphical abstract.