Silver clusters with ∼10 atoms are molecules, and specific species develop within DNA strands. These molecular metals have sparsely organized electronic states with distinctive visible and near-infrared spectra that vary with cluster size, oxidation, and shape. These small molecules also act as DNA adducts and coordinate with their DNA hosts. We investigated these characteristics using a specific cluster-DNA conjugate with the goal of developing a sensitive and selective biosensor. The silver cluster has a single violet absorption band (λ(max) = 400 nm), and its single-stranded DNA host has two domains that stabilize this cluster and hybridize with target oligonucleotides. These target analytes transform the weakly emissive violet cluster to a new chromophore with blue-green absorption (λ(max) = 490 nm) and strong green emission (λ(max) = 550 nm). Our studies consider the synthesis, cluster size, and DNA structure of the precursor violet cluster-DNA complex. This species preferentially forms with relatively low amounts of Ag(+), high concentrations of the oxidizing agent O2, and DNA strands with ≳20 nucleotides. The resulting aqueous and gaseous forms of this chromophore have 10 silvers that coalesce into a single cluster. This molecule is not only a chromophore but also an adduct that coordinates multiple nucleobases. Large-scale DNA conformational changes are manifested in a 20% smaller hydrodynamic radius and disrupted nucleobase stacking. Multidentate coordination also stabilizes the single-stranded DNA and thereby inhibits hybridization with target complements. These observations suggest that the silver cluster-DNA conjugate acts like a molecular beacon but is distinguished because the cluster chromophore not only sensitively signals target analytes but also stringently discriminates against analogous competing analytes.

Infectious diseases claim millions of lives each year. Robust and accurate diagnostics are essential tools for identifying those who are at risk and in need of treatment in low-resource settings. Inorganic complexes and metal-based nanomaterials continue to drive the development of diagnostic platforms and strategies that enable infectious disease detection in low-resource settings. In this review, we highlight works from the past 20 years in which inorganic chemistry and nanotechnology were implemented in each of the core components that make up a diagnostic test. First, we present how inorganic biomarkers and their properties are leveraged for infectious disease detection. In the following section, we detail metal-based technologies that have been employed for sample preparation and biomarker isolation from sample matrices. We then describe how inorganic- and nanomaterial-based probes have been utilized in point-of-care diagnostics for signal generation. The following section discusses instrumentation for signal readout in resource-limited settings. Next, we highlight the detection of nucleic acids at the point of care as an emerging application of inorganic chemistry. Lastly, we consider the challenges that remain for translation of the aforementioned diagnostic platforms to low-resource settings.

The trifluoropropynyl ligand -C≡CCF(3) was studied as a possible surrogate for the cyano ligand. Complexes of the type trans-[M(cyclam)(C≡CCF(3))(2)]OTf (where M = Cr(3+), Co(3+), and Rh(3+); OTf = trifluoromethanesulfonate) were prepared and then characterized by electronic spectroscopy and by cyclic voltammetry for the Co(3+) complex. The UV-vis spectra for all three bear a remarkable similarity to that of the trans-M(cyclam)(CN)(2)(+) cations. The trifluoropropynyl complex of Co(3+) shows electrochemical behavior nearly identical with that of its dicyano analogue. Metal-centered phosphorescence from the Rh(III) complex in room-temperature aqueous solution has a quantum yield of 0.12 and a lifetime of 73 μs, nearly 10 times higher than those of its dicyano analogue.

Lateral flow assays (LFAs) have been used extensively for diagnosis of various diseases and conditions because they are inexpensive, rapid, robust, and easy to use. Incorporating LFAs into undergraduate chemistry courses could enrich the curricula by providing the students with a real-world application of analytical chemistry concepts, particularly why point of care diagnostics can give false positives and false negatives. We developed an LFA module for a class of 25 undergraduate analytical chemistry students that used a hybrid (part face-to-face (F2F) and part remote) learning format. The laboratory consisted of two sessions, the first of which was conducted F2F and the second of which was conducted remotely via conferencing software. In the laboratory session, the students ran LFAs that were designed in house and that detected a well-established malaria biomarker. The students subsequently captured photos and quantified the LFA signal using a mobile-friendly web application that allows for quantification of LFA test and control lines using a smartphone camera. During the second remote session, the students constructed receiver operating characteristic curves, and this activity was used to foster a broader discussion among the students about diagnostic specificity and sensitivity. Following the conclusion of the module, we had the students complete an anonymous survey where students reported they felt an increase in comprehension regarding the topics of LFAs and diagnostic specificity versus sensitivity. We have included all data and protocols to perform this lab and believe this module is well-suited as an in-person, hybrid, or remoteonly lab or even as a lecture content supplement.

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