A New Area in Main-Group Chemistry: Zerovalent Monoatomic Silicon Compounds and Their Analogues

ConspectusMonoatomic zerovalent main-group element complexes emerged very recently and attracted increasing attention of both theoretical and experimental chemists. In particular, zerovalent silicon complexes and their congeners (metallylones) stabilized by neutral Lewis donors are of significant importance not only because of their intriguing electronic structure but also because they can serve as useful building blocks for novel chemical species. Featuring four valence electrons as two lone pairs at the central atoms, such complexes may form donor–acceptor adducts with Lewis acids. More interestingly, with the central atoms in the oxidation state of zero, they could pave a way to new classes of compounds and functional groups that are otherwise difficult to realize.In this Account, we mainly describe our contributions in the chemistry of monatomic zerovalent silicon (silylone) and germanium (germylone) supported by a chelate bis-<i>N</i>-heterocyclic carbene (bis-NHC) ligand in the context of related species developed by other groups in the meantime. Utilizing the bis-NHC stabilized chlorosilyliumylidene [:SiCl]⁺ and chlorogermyliumylidene [:GeCl]⁺ as suitable starting materials, we successfully isolated silylone (bis-NHC)Si and germylone (bis-NHC)­Ge, respectively. The electronic structures of the latter complexes established by theoretical calculations and spectroscopic data revealed that they are genuine metallylone species with electron-rich silicon(0) and germanium(0) centers. Accordingly, they can react with 1 molar equiv of GaCl₃ to form Lewis adducts (bis-NHC)­E­(GaCl₃) (E = Si, Ge) and with 2 molar equiv of ZnCl₂ to furnish (bis-NHC)­Si­(ZnCl₂)₂. Conversion of the metallylones with elemental chalcogens affords isolable monomeric silicon­(II) and germanium­(II) monochalcogenides (bis-NHC)­EX­(GaCl₃) (X = Se, Te), representing molecular heavier congeners of CO. Moreover, their reaction with elemental chalcogens can also yield monomeric silicon­(IV) and germanium­(IV) dichalcogenides (bis-NHC)­EX₂ (X = S, Se, Te) as the first isolable complexes of the molecular congeners of CO₂. Moreover, (bis-NHC)­Si could even activate CO₂ to afford the monomolecular silicon dicarbonate complex (bis-NHC)­Si­(CO₃)₂ via the formation of SiO and SiO₂ complexes as intermediates. Furthermore, starting with a chelate bis-<i>N</i>-heterocyclic silylene supported [:GeCl]⁺, we developed two bis-<i>N</i>-heterocyclic silylene stabilized germylone→Fe­(CO)₄ complexes. Our achievements in the chemistry of metallylones demonstrate that the characteristic of monatomic zerovalent silicon and its analogues can provide novel reaction patterns for access to unprecedented species and even extends the series of functional groups of these elements. With this, we can envision that more interesting zerovalent complexes of the main-group elements with unprecedented reactivity will follow in the near future

A Cyclic Germadicarbene (“Germylone”) from Germyliumylidene

By employing the chelate dicarbene <b>1</b>, the new chloro­germylium­ylidene complex <b>2</b> could be synthesized and isolated in 95% yield. Dechlorination of <b>2</b> with sodium naphthalenide furnishes the unique cyclic germadicarbene <b>3</b> which could be isolated in 45% yield. Compound <b>3</b> is the first isolable Ge(0) complex with a single germanium atom stabilized by a dicarbene. Its molecular structure is in accordance with DFT calculations which underline the peculiar electronic structure of <b>3</b> with two lone pairs of electrons at the Ge atom

A Cyclic Germadicarbene (“Germylone”) from Germyliumylidene

By employing the chelate dicarbene <b>1</b>, the new chloro­germylium­ylidene complex <b>2</b> could be synthesized and isolated in 95% yield. Dechlorination of <b>2</b> with sodium naphthalenide furnishes the unique cyclic germadicarbene <b>3</b> which could be isolated in 45% yield. Compound <b>3</b> is the first isolable Ge(0) complex with a single germanium atom stabilized by a dicarbene. Its molecular structure is in accordance with DFT calculations which underline the peculiar electronic structure of <b>3</b> with two lone pairs of electrons at the Ge atom

Synthesis and Unexpected Reactivity of Germyliumylidene Hydride [:GeH]⁺ Stabilized by a Bis(<i>N</i>‑heterocyclic carbene)borate Ligand

Employing the potassium salt of the monoanionic bis­(<i>NHC</i>)­borate <b>1</b> (<i>NHC</i> = <i>N</i>-<i>H</i>eterocyclic <i>C</i>arbene) enables the synthesis and isolation of the bis­(<i>NHC</i>)­borate-stabilized chlorogermyliumylidene precursor <b>2</b> in 61% yield. A Cl/H exchange reaction of <b>2</b> using potassium tri<i>sec</i>.-butylborhydride as a hydride source leads to the isolation of the first germyliumylidene hydride [HGe:⁺] complex <b>3</b> in 91% yield. The Ge­(II)–H bond in the latter compound has an unexpected reactivity as shown by the reaction with the potential hydride scavenger [Ph₃C]⁺[B­(C₆F₅)₄]⁻, furnishing the corresponding HGe: → CPh₃ cation in the ion pair <b>4</b> as initial product. Compound <b>4</b> liberates HCPh₃ in the presence of <b>3</b> to give the unusual dinuclear HGe: → Ge: cation in <b>5</b>. The latter represents the first three-coordinate dicationic Ge­(II) species stabilized by an anionic bis­(<i>NHC</i>) chelate ligand and a Ge­(II) donor. All novel compounds were fully characterized, including X-ray diffraction analyses

An NGS-Independent Strategy for Proteome-Wide Identification of Single Amino Acid Polymorphisms by Mass Spectrometry

Detection of proteins containing single amino acid polymorphisms (SAPs) encoded by nonsynonymous SNPs (nsSNPs) can aid researchers in studying the functional significance of protein variants. Most proteogenomic approaches for large-scale SAPs mapping require construction of a sample-specific database containing protein variants predicted from the next-generation sequencing (NGS) data. Searching shotgun proteomic data sets against these NGS-derived databases allowed for identification of SAP peptides, thus validating the proteome-level sequence variation. Contrary to the conventional approaches, our study presents a novel strategy for proteome-wide SAP detection without relying on sample-specific NGS data. By searching a deep-coverage proteomic data set from an industrial thermotolerant yeast strain using our strategy, we identified 337 putative SAPs compared to the reference genome. Among the SAP peptides identified with stringent criteria, 85.2% of SAP sites were validated using whole-genome sequencing data obtained for this organism, which indicates high accuracy of SAP identification with our strategy. More interestingly, for certain SAP peptides that cannot be predicted by genomic sequencing, we used synthetic peptide standards to verify expression of peptide variants in the proteome. Our study has provided a unique tool for proteogenomics to enable proteome-wide direct SAP identification and capture nongenetic protein variants not linked to nsSNPs

Highly Selective and Large Scale Mass Spectrometric Analysis of 4‑Hydroxynonenal Modification via Fluorous Derivatization and Fluorous Solid-Phase Extraction

Modification of proteins with 4-hydroxynonenal (HNE) is known to alter the function of proteins and regulate the associated biological processes in eukaryotic cells. The development of mass spectrometry (MS) makes high-throughput analysis of HNE modification accessible. However, the identification of HNE modification is still hampered by the low frequency of this modification. Therefore, only a limited number of HNE modification sites have been identified. The enrichment of HNE-modified peptides is critical for the MS analysis of this modification because of its low abundance. Herein, we explored a novel strategy for specifically extracting the HNE-modified peptides using fluorous derivatization through oxime click chemistry combined with following fluorous solid-phase extraction (FSPE). This oxime click chemistry-based derivatization is highly efficient (with a yield of almost 100%) and fast (30 min). Because of the hydrophobicity of the fluorous tag, the signal of fluorous-derivatized HNE-modified peptides was greatly enhanced, making the detection of HNE-modified peptides sensitive. The FSPE further allowed the selective enrichment of fluorous-derivatized HNE-modified peptides from salt solutions and complex mixtures with specificity. Finally, 673 HNE modification sites (607 histidine sites, 60 cysteine sites, 5 lysine sites, and 1 arginine site) on 661 HNE-modified peptides mapped to 432 proteins were successfully identified using this novel approach, which presented the largest data set of HNE modification in MCF-7 cells. Three identified proteins were validated by Western blotting

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

Tubulin is known to undergo unique post-translational modifications (PTMs), such as detyrosination and polyglutamylation, particularly in the unstructured carboxy-terminal tails (CTTs). However, more conventional PTMs of tubulin and their roles in the regulation of microtubule properties and functions remain poorly defined. Here, we report the comprehensive profiling of tubulin phosphorylation, acetylation, ubiquitylation, and <i>O</i>-GlcNAcylation in HeLa cells with a proteomic approach. Our tubulin-targeted analysis has identified 80 residues bearing single or multiple conventional PTMs including 24 novel PTM sites not covered in previous global proteomic surveys. By using a series of PTM-deficient or PTM-mimicking mutants, we further find that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. In addition, these tubulin PTMs have distinct effects on the retrograde transport of adenoviruses along microtubules. These findings thus enlarge the repertoire of tubulin PTMs and foster our understanding of their versatile roles in the regulation of microtubule dynamics and cellular functions

Dual Reactivity of a Stable Zwitterionic N-Heterocyclic Silylene and Its Carbene Complex Probed with Muonium

The reactivity of the multifunctional cyclic silylene <b>4</b> and its carbene complex <b>5</b> have been investigated by a combination of muon spin spectroscopy and computation. The free radicals formed by muonium (Mu) addition to <b>4</b> were identified, showing that there are two dominant sites of free radical attack: on the Si atom and on the exocyclic methylene carbon. Reaction of muonium with <b>5</b> also produced two radicals, but with markedly different hyperfine constants. For both compounds avoided level-crossing resonance spectra and calculation of hyperfine constants show that one of the radicals results from Mu addition to the methylene group, yielding radicals <b>4a</b> and <b>5a</b>. Each contains a muoniated methyl group, −CH₂Mu, which undergoes restricted rotation with respect to the plane of the ring. For <b>4</b> the second product is readily assigned as the muoniated silyl radical <b>4b</b>, on the grounds of its high muon hyperfine constant (716 MHz). The second product from <b>5</b> shows instead a very small coupling constant, 19 MHz, assignable to the muoniated complex <b>5b</b>, in which the spin density has been transferred from the silicon to the carbenic carbon

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

Tubulin is known to undergo unique post-translational modifications (PTMs), such as detyrosination and polyglutamylation, particularly in the unstructured carboxy-terminal tails (CTTs). However, more conventional PTMs of tubulin and their roles in the regulation of microtubule properties and functions remain poorly defined. Here, we report the comprehensive profiling of tubulin phosphorylation, acetylation, ubiquitylation, and <i>O</i>-GlcNAcylation in HeLa cells with a proteomic approach. Our tubulin-targeted analysis has identified 80 residues bearing single or multiple conventional PTMs including 24 novel PTM sites not covered in previous global proteomic surveys. By using a series of PTM-deficient or PTM-mimicking mutants, we further find that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. In addition, these tubulin PTMs have distinct effects on the retrograde transport of adenoviruses along microtubules. These findings thus enlarge the repertoire of tubulin PTMs and foster our understanding of their versatile roles in the regulation of microtubule dynamics and cellular functions

Proteomic Profiling and Functional Characterization of Multiple Post-Translational Modifications of Tubulin

Tubulin is known to undergo unique post-translational modifications (PTMs), such as detyrosination and polyglutamylation, particularly in the unstructured carboxy-terminal tails (CTTs). However, more conventional PTMs of tubulin and their roles in the regulation of microtubule properties and functions remain poorly defined. Here, we report the comprehensive profiling of tubulin phosphorylation, acetylation, ubiquitylation, and <i>O</i>-GlcNAcylation in HeLa cells with a proteomic approach. Our tubulin-targeted analysis has identified 80 residues bearing single or multiple conventional PTMs including 24 novel PTM sites not covered in previous global proteomic surveys. By using a series of PTM-deficient or PTM-mimicking mutants, we further find that tubulin phosphorylation and acetylation play important roles in the control of microtubule assembly and stability. In addition, these tubulin PTMs have distinct effects on the retrograde transport of adenoviruses along microtubules. These findings thus enlarge the repertoire of tubulin PTMs and foster our understanding of their versatile roles in the regulation of microtubule dynamics and cellular functions