One-Step Route to Luminescent Au₁₈SG₁₄ in the Condensed Phase and Its Closed Shell Molecular Ions in the Gas Phase

We report a one-step route for the synthesis of highly luminescent and water-soluble Au₁₈SG₁₄ (SG- glutathione in thiolate form) in nearly pure form using a slow reduction process. The cluster shows step-like behavior in its absorption profile. It emits red light in both aqueous and solid state under UV illumination. Quantum yield of the cluster is 0.053, nearly 25-fold higher than that of Au₂₅SG₁₈. The cluster exhibits distinct features corresponding to multiply charged ions in electrospray ionization mass spectrometry. This composition is also confirmed from MALDI MS along with other quantitative analyses. The cluster makes closed shell molecular ions in the gas phase. The possibility of making clusters of different core sizes is also demonstrated. The simplicity of this method and identification of the cluster with exact composition may facilitate the exploration of experimental and theoretical research on this material

Coalescence of Atomically Precise Clusters on Graphenic Surfaces

The interaction of ultrasmall metal clusters with surfaces of graphene is important for developing promising future applications of graphenic materials. In the experiment, chemically synthesized reduced graphene oxide (RGO) in water was mixed with Au₂₅SR₁₈ (where SR, SCH₂CH₂Ph, is a ligand protecting the cluster core) in tetrahydrofuran, and a completely new cluster, larger in mass, was formed at the liquid–liquid interface. Matrix assisted laser desorption ionization mass spectrometry of the product attached to RGO show that the peak due to Au₂₅SR₁₈ disappears gradually upon reaction and a single sharp peak referred to here as “135 ± 1 kDa cluster” appears. The composition of the new cluster is very close to the well-known magic cluster, Au₁₄₄SR₆₀ while the peak maximum is at Au₁₃₅SR₅₇. The formation of 35 ± 1 kDa cluster from the parent Au₂₅ is proposed to be governed by the trapping of smaller clusters in a deep potential well generated at the graphene surface. We theoretically model the active role of the surface in stabilizing the large clusters. Our studies indicate a general mechanism of stabilization of clusters of precise size via the competition between the interfacial fluctuations and the energy scales of interaction of the clusters with the surface. The chemical transformation occurs at deformable surfaces at reduced particle densities which is in good agreement with the theoretical model. Transformations of this kind are important in controlled tuning of particles at graphenic surfaces

Direct Evidence for Excited Ligand Field State-based Oxidative Photoredox Chemistry of a Cobalt(III) Polypyridyl Photosensitizer

Increasing interest in sustainable chemistry coupled with the quest to explore new reactivity has spurred research on first-row transition metal complexes for potential applications in a variety of settings. One of the more active areas of research is photoredox catalysis, where the synthetically tunable nature of their electronic structures provides a rich palette of options for tailoring their reactivity to a desired chemical transformation. Understanding the mechanism of excited-state reactivity is critical for the informed development of next-generation catalysts, which in turn requires information concerning the propensity of their electronic excited states to engage in the desired electron or energy transfer processes. Herein we provide direct evidence of the highly oxidizing nature of the lowest-energy ligand-field (LF) excited state of a first-row d6-low-spin Co­(III) photosensitizer [Co­(4,4′-Br2bpy)3]3+ (where 4,4′-Br2bpy is 4,4′-dibromo-2,2′-bipyridine). The redox potential associated with the LF excited state of the Co­(III) complex was bracketed by performing bimolecular quenching studies by using a series of simple organic electron donors. Time-resolved absorption spectroscopy confirmed a dynamic quenching process attributed to reductive quenching of the lowest-energy ligand-field excited state of the Co­(III) chromophore. Analysis of the Stern–Volmer plots for each chromophore-quencher pair revealed a limiting value of Ered* ∼ 1.25 V vs Fc/Fc+ for the metal-centered excited state, which is significantly stronger than that of more commonly employed transition metal-based photoredox agents such as [Ru­(bpy)3]2+ (Ered* = 0.32 V vs Fc/Fc+) and [Ir­(ppy)2(bpy)]+ (Ered* = 0.27 V vs Fc/Fc+). These results suggest that this class of chromophores could find utility in applications requiring the activation of oxidatively resistant organic substrates for photoredox catalysis

Synthesis and Biophysical Properties of Triazole-Incorporated PMOs (TzPMOs): A Convergent, Click Ligation Approach

The synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) incorporating single or double triazole rings in the backbone has been achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The synthetic approach implemented is fundamentally convergent, involving the ligation of a 5′-azide PMO fragment to a 3′-alkyne fragment both in solution and on solid support. To access the 3′-alkyne PMO fragment, we synthesized 3′-N-propargyl chlorophosphoramidate morpholino monomers for all four nucleobases. The resulting triazole-incorporated PMOs (TzPMOs) have exhibited comparable or improved binding affinity toward complementary deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) strands compared to its regular analogues. Finally, a full-length TzPMO was designed to target the Nanog gene, demonstrating almost identical hybridization properties when compared to its regular version. Circular dichroism studies revealed a B-type helical conformation for the duplexes formed by TzPMOs

Synthesis and Biophysical Studies of High-Affinity Morpholino Oligomers Containing G‑Clamp Analogs

Successful syntheses of chlorophosphoramidate morpholino monomers containing tricyclic cytosine analogs phenoxazine, G-clamp, and G8AE-clamp were accomplished. These modified monomers were incorporated into 12-mer oligonucleotides using trityl-chemistry by an automated synthesizer. The resulting phosphorodiamidate morpholino oligomers, containing a single G-clamp, demonstrated notably higher affinity for complementary RNA and DNA compared to the unmodified oligomers under neutral and acidic conditions. The duplexes of RNA and DNA with G-clamp-modified oligomers adopt a B-type helical conformation, as evidenced by CD-spectra and show excellent base recognition properties. Binding affinities were sequence and position dependent

Dissociation of Gas Phase Ions of Atomically Precise Silver Clusters Reflects Their Solution Phase Stability

We report an attempt to probe into the energy demand of the fragmentation of atomically precise silver clusters using collision induced dissociation mass spectrometry. Energy resolved collisions of several gas phase ions of clusters, Ag₂₉(S₂R)₁₂, Ag₂₅(SR)₁₈, and Ag₄₄(SR)₃₀, reveal distinct fragmentation kinetics involving charge separation. The fragmentation pattern of [Ag₂₅(SR)₁₈]⁻ is found to be different from its structural analog, [Au₂₅(SR)₁₈]⁻. Survival yield analysis has been used to establish a direct comparison between the stability of the ions of these clusters, which reveals that [Ag₂₉(S₂R)₁₂]^3– is the most stable cluster ion, followed by [Ag₂₅(SR)₁₈]⁻ and [Ag₄₄(SR)₃₀]^4–. Gas phase stabilities reflect their solution phase stabilities, indicating that the molecular nature of the clusters is retained in the gas phase, too. We further report that fragmentation occurs in a stepwise fashion, conserving the closed shell electronic stability of the parent ion at each step. Such studies are important in understanding the electronic and geometric stability of cluster ions and their fragments

Visible-Light Copper Nanocluster Catalysis for the C–N Coupling of Aryl Chlorides at Room Temperature

Activation of aryl chlorides in cross-coupling reactions is a long-standing challenge in organic synthesis that is of great interest to industry. Ultrasmall (<3 nm), atomically precise nanoclusters (NCs) are considered one of the most promising catalysts due to their high surface area and unsaturated active sites. Herein, we introduce a copper nanocluster-based catalyst, [Cu61(StBu)26S6Cl6H14] (Cu61NC) that enables C–N bond-forming reactions of aryl chlorides under visible-light irradiation at room temperature. A range of N-heterocyclic nucleophiles and electronically and sterically diverse aryl/hetero chlorides react in this new Cu61NC-catalyzed process to afford the C–N coupling products in good yields. Mechanistic studies indicate that a single-electron-transfer (SET) process between the photoexcited Cu61NC complex and aryl halide enables the C–N-arylation reaction

Synthesis of Phosphorodiamidate Morpholino Oligonucleotides Using Trityl and Fmoc Chemistry in an Automated Oligo Synthesizer

Phosphorodiamidate morpholino oligonucleotides (PMOs) constitute 3 out of the 11 FDA-approved oligonucleotide-based drugs in the last 6 years. PMOs can effectively silence disease-causing genes and modify splicing. However, PMO synthesis has remained challenging for a variety of reasons: inefficient deprotection and coupling methods and instability of monomers. Here, we report the development of a suitable combination of resin supports, deblocking and coupling reagents for synthesizing PMOs using either trityl or Fmoc-protected chlorophosphoramidate monomers. The synthesized PMOs using both the methods on a solid support have been validated for gene silencing in a zebrafish model. The protocol was successfully transferred into an automated DNA synthesizer to make several sequences of PMOs, demonstrating for the first time the adaptation of regular PMOs in a commercial DNA synthesizer. Moreover, PMOs with longer than 20-mer sequences, including FDA-approved Eteplirsen (30-mer), were achieved in >20% overall yield that is superior to previous reports. Hybridization study shows that PMOs exhibit a higher binding affinity toward complementary DNA relative to the DNA/DNA duplex (>6 °C). Additionally, the introduction of Fmoc chemistry into PMOs opens up the possibility for PMO synthesis in commercial peptide synthesizers for future development

Intercluster Reactions between Au₂₅(SR)₁₈ and Ag₄₄(SR)₃₀

We present the first example of intercluster reactions between atomically precise, monolayer protected noble metal clusters using Au₂₅(SR)₁₈ and Ag₄₄(SR)₃₀ (RS– = alkyl/aryl thiolate) as model compounds. These clusters undergo spontaneous reaction in solution at ambient conditions. Mass spectrometric measurements both by electrospray ionization and matrix assisted laser desorption ionization show that the reaction occurs through the exchange of metal atoms and protecting ligands of the clusters. Intercluster alloying is demonstrated to be a much more facile method for heteroatom doping into Au₂₅(SR)₁₈, as observed by doping up to 20 Ag atoms. We investigated the thermodynamic feasibility of the reaction using DFT calculations and a tentative mechanism has been presented. Metal core-thiolate interfaces in these clusters play a crucial role in inducing these reactions and also affect rates of these reactions. We hope that our work will help accelerate activities in this area to establish chemistry of monolayer protected clusters

Simple and Efficient Separation of Atomically Precise Noble Metal Clusters

There is an urgent need for accessible purification and separation strategies of atomically precise metal clusters in order to promote the study of their fundamental properties. Although the separation of mixtures of atomically precise gold clusters Au₂₅L₁₈, where L are thiolates, has been demonstrated by advanced separation techniques, we present here the first separation of metal clusters by thin-layer chromatography (TLC), which is simple yet surprisingly efficient. This method was successfully applied to a binary mixture of Au₂₅L₁₈ with different ligands, as well as to a binary mixture of different cluster cores, Au₂₅ and Au₁₄₄, protected with the same ligand. Importantly, TLC even enabled the challenging separation of a multicomponent mixture of mixed-monolayer-protected Au₂₅ clusters with closely similar chemical ligand compositions. We anticipate that the realization of such simple yet efficient separation technique will progress the detailed investigation of cluster properties