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Journal of the American Chemical Society 145(20), 11440 - 11448 (2023). doi:10.1021/jacs.3c03270, Silafulleranes with endohedral Cl$^−$ ions are a unique,scarcely explored class of structurally well-defined silicon clustersand host-guest complexes. Herein, we report regioselectivederivatization reactions on the siladodecahedrane [nBu$_4$N][Cl@Si$_{20}$(SiCl$_3$)$_{12}$Cl$_8$] ([nBu$_4$N][1]), which has its cluster surfacedecorated with 12 SiCl$_3$ and 8 Cl substituents in perfect T$_h$ symmetry. The room-temperature reaction of [nBu$_4$N][1] withexcess iBu$_2$AlH in ortho-difluorobenzene (oDFB) furnishesperhydrogenated [nBu$_4$N][Cl@Si$_{20}$(SiH$_3$)$_{12}$H$_8$] ([nBu$_4$N][2]) in 50% yield; the non-pyrophoric [2]$^−$ is the largest structurallyauthenticated (by X-ray diffraction) hydridosilane known to date. Asimple switch from pure oDFB to an oDFB/Et$_2$O solvent mixturesuppresses core hydrogenation and results in the formation of[nBu$_4$N][Cl@Si$_{20}$(SiH$_3$)$_{12}$Cl$_8$] ([nBu$_4$N][3]). In addition to the exhaustive Cl/H exchange at all 44 Si−Cl bonds of [1]$^−$ and theregioselective 36-fold silyl group hydrogenation, we achieved the simultaneous introduction of Me substituents at all 8 SiCl verticesalong with the conversion of all 12 SiCl$_3$ to SiH$_3$ groups by treating [nBu$_4$N][1] with Me$_2$AlH/Me$_3$Al in oDFB ([nBu$_4$N][Cl@Si$_{20}$(SiH$_3$)$_{12}$Me$_8$], [nBu$_4$N][4]; 73%). Quantum-chemical free-energy calculations find an SN$_2$-Si-type hydrogenation of theexohedral SiCl$_3$ moieties in [1]$^−$ (trigonal-bipyramidal intermediate) slightly preferred over metathesis-like SNi-Si substitutions (four-membered transition state). Cage hydrogenation likely occurs via SNi-Si processes. The experimentally demonstrated influenceof an Et$_2$O co-solvent, which drastically increases the respective reaction barriers, is attributed to the increased stability of theresulting iBu$_2$AlH-OEt$_2$ adduct and its higher steric bulk compared to free iBu$_2$AlH., Published by ACS Publications, Washington, DC

We report the reactivity of 1,2,3-trizole-derived mesoionic N-heterocyclic olefins toward α-diazoesters.

Extensive dispersion-corrected DFT calculations are used to explore both neutral and ionic approaches to synthesize a broad range of transition metal radical complexes and potential thermal radical initiators.

Reactions of (tBuO2CN)2 with FLPs inducing loss of CH2CMe2; using strong bases [Hbase]2 [((C6F5)3BO2CN)2] are isolated whereas with weaker bases diazene derivatives are obtained.

We present a new benchmark set consisting of 16 large non-covalently bound systems (LNCI16) ranging from 380 up to 1988 atoms and featuring diverse interaction motives. Gas-phase interaction energies are calculated with various composite DFT, semi-empirical quantum mechanical (SQM), and force field (FF) methods and are evaluated using accurate DFT reference values. Of the employed QM methods, PBEh-3c proves to be the most robust for large systems with a relative mean absolute deviation (relMAD) of 8.5% with respect to the reference interaction energies. r2SCAN-3c yields an even smaller relMAD, at least for the subset of complexes for which the calculation could be converged, but is less robust for systems with smaller HOMO–LUMO gaps. The inclusion of Fock-exchange is therefore important for the description of very large non-covalent interaction (NCI) complexes in the gas phase. GFN2-xTB was found to be the best performer of the SQM methods with an excellent result of only 11.1% deviation. From the assessed force fields, GFN-FF and GAFF achieve the best accuracy. Considering their low computational costs, both can be recommended for routine calculations of very large NCI complexes, with GFN-FF being clearly superior in terms of general applicability. Hence, GFN-FF may be routinely applied in supramolecular synthesis planning.1 Introduction2 The LNCI16 Benchmark Set3 Computational Details4 Generation of Reference Values5 Results and Discussion6 Conclusions

Abstract The previously not studied photochemical degradation of sulfamethoxazole (SMX) to the isomer of SMX (ISO) was measured via a polychromatic (Xe) and a monochromatic (Hg) light source and accompanied by quantum chemical DFT calculations. In addition to the $$\mathrm{p}K_\mathrm{a} = \;7.0 \pm 0.1$$ p K a = 7.0 ± 0.1 of ISO, tautomer-dependent properties such as the $$K_\mathrm{OW}$$ K OW were measured and theoretically confirmed by DFT. The kinetics in solutions below and above the $$\mathrm{p}K_\mathrm{a} = 5.6$$ p K a = 5.6 of SMX were studied for the available and quantifiable products SMX, ISO, 3-amino-5-methylisoxazole (AMI), 2-amino-5-methyloxazole (AMO), and sulfanilic acid (SUA). The quantum yields of the neutral ($$\Phi _\mathrm{N}$$ Φ N ) and anionic $$\Phi _\mathrm{A}$$ Φ A ) forms of SMX ($$\Phi _\mathrm{A} = 0.03 \pm 0.001$$ Φ A = 0.03 ± 0.001 , $$\Phi _\mathrm{N} = 0.15 \pm 0.01$$ Φ N = 0.15 ± 0.01 ) and ISO ($$\Phi _\mathrm{A} = 0.05 \pm 0.01$$ Φ A = 0.05 ± 0.01 and $$\Phi _\mathrm{N} = 0.06 \pm 0.02$$ Φ N = 0.06 ± 0.02 ) were found to be wavelength-independent. In a competitive reaction to the formation of ISO from SMX, the degradation product TP271 is formed. Various proposed structures for TP271 described in the literature have been studied quantum mechanically and can be excluded for thermodynamic reasons. In real samples in a northern German surface water in summer 2021 mean concentrations of SMX were found in the range of 120 ng/L. In agreement with the pH-dependent yields, concentrations of ISO were low in the range of 8 ng/L. Graphical abstract

An automated and broadly applicable workflow for the description of solvation effects in an explicit manner is introduced. This method, termed quantum cluster growth (QCG), is based on the semiempirical GFN2-xTB/GFN-FF methods, enabling efficient geometry optimizations and MD simulations. Fast structure generation is provided using the intermolecular force field xTB-IFF. Additionally, the approach uses an efficient implicit solvation model for the electrostatic embedding of the growing clusters. The novel QCG procedure presents a robust cluster generation tool for subsequent application of higher-level (e.g., DFT) methods to study solvation effects on molecular geometries explicitly or to average spectroscopic properties over cluster ensembles. Furthermore, the computation of the solvation free energy with a supermolecular approach can be carried out with QCG. The underlying growing process is physically motivated by computing the leading-order solute-solvent interactions first and can account for conformational and chemical changes due to solvation for low-energy barrier processes. The conformational space is explored with the NCI-MTD algorithm as implemented in the CREST program, using a combination of metadynamics and MD simulations. QCG with GFN2-xTB yields realistic solution geometries and reasonable solvation free energies for various systems without introducing many empirical parameters. Computed IR spectra of some solutes with QCG show a better match to the experimental data compared to well-established implicit solvation models.

The mechanism of CO2 hydrogenation with BH3NH3 in water as a protic and green solvent to produce formate salts with an additional base is explored by DFT calculations, paving the way to more atom-efficient CO2 reduction under milder conditions.

An environmentally responsible synthesis of tezacaftor, a drug approved in 2018 currently in use for treatment of cystic fibrosis, is described utilizing chemistry in water enabled by the nonionic surfactant TPGS-750-M.

A C3 symmetric building block for self-assembly.

Selective defluorinative functionalization of trifluoromethyl ketones is a long-standing challenge owing to the exhaustive mode of the process. To meet the demands for the installation of the gem-difluoromethylene unit for the construction of the molecular architectures of well-known pharmaceuticals and agrochemicals, a distinct pathway is thereby highly desirable. Here, we introduce a protocol that allows the divergent synthesis of gem-difluoromethylene group containing tetrahydrofuran derivatives and linear ketones via single C-F bond activation of trifluoromethyl ketones using visible-light photoredox catalysis in the presence of suitable olefins as trapping partner. The choice of appropriate solvent and catalyst plays a significant role in controlling the divergent behavior of this protocol. Highly reducing photo-excited catalysts are found to be responsible for the generation of α,α-difluoromethyl ketone (DFMK) radicals as the key intermediate via a SET process. This protocol also results in a high diastereoselectivity towards the formation of partially fluorinated cyclic ketal derivatives with simultaneous construction of one C-C and two C-O bonds. State-of-the-art DFT calculations are performed to address the origin of diastereoselectivity as well as the divergence of this protocol.

A new composite density functional theory (DFT) method is presented. It is based on ωB97X-V as one of the best-performing density functionals for the GMTKN55 thermochemistry database and completes the family of “3c” methods toward range-separated hybrid DFT. This method is consistently available for all elements up to Rn (Z = 1–86). Its further key ingredients are a polarized valence double- ζ (vDZP) Gaussian basis set, which was fully optimized in molecular DFT calculations, in combination with large-core effective core potentials and a specially adapted D4 dispersion correction. Unlike most existing double- ζ atomic orbital sets, vDZP shows only small basis set superposition errors (BSSEs) and can compete with standard sets of triple- ζ quality. Small residual BSSE effects are efficiently absorbed by the D4 damping scheme, which overall eliminates the need for an explicit treatment or empirical corrections for BSSE. Thorough tests on a variety of thermochemistry benchmark sets show that the new composite method, dubbed ωB97X-3c, is on par with or even outperforms standard hybrid DFT methods in a quadruple-zeta basis set at a small fraction of the computational cost. Particular strengths of this method are the description of non-covalent interactions and barrier heights, for which it is among the best-performing density functionals overall.

Chemical communications 59(48), 7459 - 7462 (2023). doi:10.1039/D3CC02142D, Starting from the perhydrogenated silafullerane [$n$Bu$_4$N][Cl@Si$_{20}$(SiH$_3$)$_{12}$H$_8$], treatment with BBr$_3$ leads to partially and exhaustively brominated clusters, [$n$Bu$_4$N][Cl@Si$_{20}$(SiBr$_2$H)$_{12}$Br$_8$] (120 eq.BBr$_3$, room temperature, 30 min) and [$n$Bu$_4$N][Cl@Si$_{20}$(SiBr$_3$)$_{12}$Br$_8$](300 eq. BBr$_3$, 130 8C, 3 d). Perbromination is accompanied by amassively increased steric strain on the cluster surface, whichexplains why our approach achieves regioselective derivatizationof the Si$_{32}$ framework when mild conditions are maintained. PartialBr/H exchange on [$n$Bu$_4$N][Cl@Si$_{20}$(SiBr$_2$H)$_{12}$Br$_8$] (30 eq. iBu$_2$AlH,room temperature, 16 h) affords [$n$Bu$_4$N][Cl@Si$_{20}$(SiH$_3$)$_{12}$Br$_8$]., Published by Royal Society of Chemistry, Cambridge

While the color of metallic gold is a prominent and well-investigated example for the impact of relativistic effects, much less is known regarding the influence on its melting and boiling point (MP/BP). To remedy this situation, this work takes on the challenging task of exploring the phase transitions of the Group 11 coinage metals Cu, Ag, and Au through nonrelativistic (NR) and scalar/spin-orbit relativistic (SR/SOR) Gibbs energy calculations with λ-scaled density-functional theory (λDFT). At the SOR level, the calculations provide BPs in excellent agreement with experimental values (1%), while MPs exhibit more significant deviations (2-10%). Comparing SOR calculations to those conducted in the NR limit reveals some remarkably large and, at the same time, some surprisingly small relativistic shifts. Most notably, the BP of Au increases by about 800 K due to relativity, which is in line with the strong relativistic increase of the cohesive energy, whereas the MP of Au is very similar at the SOR and NR levels, defying the typically robust correlation between MP and cohesive energy. Eventually, an inspection of thermodynamic quantities traces the trend-breaking behavior of Au back to phase-specific effects in liquid Au, which render NR Au more similar to SOR Ag, in line with a half-a-century-old hypothesis of Pyykkö.

Modeling intermolecular interactions of complex non-covalent structures is important in many areas of chemistry. To facilitate the generation of reasonable dimer, oligomer, and general aggregate geometries, we introduce an automated computational interaction site screening (aISS) workflow. This easy-to-use tool combines a genetic algorithm employing the intermolecular force-field xTB-IFF for initial search steps with the general force-field GFN-FF and the semi-empirical GFN2-xTB method for geometry optimizations. Compared with the alternative CREST program, aISS yields similar results but with computer time savings of 1-3 orders of magnitude. This allows for the treatment of systems with thousands of atoms composed of elements up to radon, e.g., metal-organic complexes, or even polyhedra and zeolite cut-outs which were not accessible before. Moreover, aISS can identify reactive sites and provides options like site-directed (user-guided) screening.

Recently, it was shown that the double Ca-H-Ca-bridged calcium hydride cation dimer [LCaH

Synthesis of value-added products from simple C1 feedstocks is an attractive alternative avenue to traditional fossil fuels. Hexa-substituted benzene derivatives are highly useful molecules but are often challenging to prepare. Herein, we report that the lithium complex [(Ph2 P(S))2 CLi2 (THF)]2 1 reacts with CO lead to C-C bond formation and migration of a Ph2 P(S)-fragment affording 2. Subsequent reaction with N2 O results in oxidative cleavage of a P-C bond affording [Ph2 P(S)OLi(THF)2 ]2 4 and the anionic ketene-derivative Ph2 P(S)CCOLi(THF)2 5. Heating 5 prompts cyclotrimerization giving the hexa-substituted benzene derivative [Ph2 P(S)CCOLi(THF)2 ]3 6 regioselectively. This transition metal-free protocol to a hexa-substituted benzene is viable on a gram scale and permits the incorporation of 13 C labels. The mechanisms of these reactions are detailed via extensive DFT computations.

The calculation of optical rotation (OR, [α]D) for nonrigid molecules was limited to small systems due to the challenging problem of generating reliable conformer ensembles, calculating accurate Boltzmann populations and the extreme sensitivity of the OR to the molecules' three-dimensional structure. Herein, we describe and release the crenso workflow for the automated computation of conformer ensembles in solution and corresponding [α]D values for flexible molecules. A comprehensive set of 28 organic drug molecules (28-144 atoms) with experimentally determined values is used in our assessment. In all cases, the correct OR sign is obtained with an overall mean relative deviation of 72% (mean absolute deviation of 82 °[dm(g/cm3)]-1 for experimental values in the range -160 to 287 °[dm(g/cm3)]-1). We show that routine [α]D computations for very flexible, biologically active molecules are both feasible and reproducible in about a day of computation time on a standard workstation computer. Furthermore, we observed that the effect of energetically higher-lying structures in the ensemble on the OR is often averaged out and that in 23 out of 28 cases, the correct OR sign is obtained by just considering only the lowest free energy conformer. In four example cases, we show that the approach can also describe the OR of pairs of flexible diastereomers properly. In summary, even very sensitive, multifactorial physicochemical properties appear reliably predictable with minimal user input from efficiently automated quantum chemical methods.

Due to the principle lack of systematic improvement possibilities of density functional theory, careful assessment of the performance of density functional approximations (DFAs) on well-designed benchmark sets, for example, for reaction energies and barrier heights, is crucial. While main-group chemistry is well covered by several available sets, benchmark data for transition metal chemistry is sparse. This is especially the case for larger, chemically relevant molecules. Addressing this issue, we recently introduced the MOR41 benchmark which covers chemically relevant reactions of closed-shell complexes. In this work, we extend these efforts to single-reference open-shell systems and introduce the "reactions of open-shell single-reference transition metal complexes" (ROST61) benchmark set. ROST61 includes accurate coupled-cluster reference values for 61 reaction energies with a mean reaction energy of -42.8 kcal mol-1. Complexes with 13-93 atoms covering 20 d-block elements are included, but due to the restriction to single-reference open-shell systems, important elements such as iron or platinum could not be taken into account, or only to a small extent. We assess the performance of 31 DFAs in combination with three London dispersion (LD) correction schemes. Further, DFT-based composite methods, MP2, and a few semiempirical quantum chemical methods are evaluated. Consistent with the results for the MOR41 closed-shell benchmark, we find that the ordering of DFAs according to Jacob's ladder is preserved and that adding an LD correction is crucial, clearly improving almost all tested methods. The recently introduced r2SCAN-3c composite method stands out with a remarkable mean absolute deviation (MAD) of only 2.9 kcal mol-1, which is surpassed only by hybrid DFAs with low amounts of Fock exchange (e.g., 2.3 kcal mol-1 for TPSS0-D4/def2-QZVPP) and double-hybrid (DH) DFAs but at a significantly higher computational cost. The lowest MAD of only 1.6 kcal mol-1 is obtained with the DH DFA PWPB95-D4 in the def2-QZVPP basis set approaching the estimated accuracy of the reference method. Overall, the ROST61 set adds important reference data to a sparsely sampled but practically relevant area of chemistry. At this point, it provides valuable orientation for the application and development of new DFAs and electronic structure methods in general.

N-Benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, easily obtained from aromatic aldehydes and anilides of dichloroacetic acid under Darzens condensation conditions, proved to be excellent starting compounds for the synthesis of 3-hydroxyindolin-2-ones, cyclohepto[b]pyrrole-2,3-diones, and 1-azaspiro[4.5]deca-3,6,9-triene-2-ones via the C(sp2)-C(sp2) bond formation in the first case and C(sp2)-C(sp3) bond formation in the second and third cases. Under optimized reaction conditions, 3-hydroxyindolin-2-ones are obtained in a one-pot process, which involves the treatment of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides with CF3CO2H or AcOH/H2SO4. In the case of intramolecular cyclization, the detailed reaction channels depend strongly on the substituents present in the anilide component and in the aromatic ring of the aldehyde component of N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides, as well as the temperature and duration of the reaction. A combined experimental and DFT mechanistic study of the formation of 1-benzyl-3-hydroxy-4-arylquinolin-2(1H)-ones showed that there are three competing reaction channels: (a) ring-closure via the ipso site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the ortho site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro-N-(4-methoxybenzyl)-N-phenylacetamide.

The metal‐free catalytic hydrogenation of secondary carboxylic acid amides is developed. The reduction is realized by two new catalytic reactions. First, the amide is converted into the imidoyl chloride by triphosgene (CO(OCCl3)2) using novel phosphorus(V) catalysts. Second, the in situ generated imidoyl chlorides are hydrogenated in high yields by an FLP‐catalyst. Mechanistic and quantum mechanical calculations support an autoinduced catalytic cycle for the hydrogenation with chloride acting as unusual Lewis base for FLP‐mediated H2‐activation., The hydrogenation of secondary carboxylic acid amides by combined phosphane oxide and frustrated Lewis pair catalysis is described. The reaction proceeds under mild conditions and displays excellent functional group tolerance. Kinetic and quantum‐chemical experiments support the autoinduced catalytic cycle with chloride as active Lewis base for the hydrogen activation.

The vapor pressure is a specific and temperature-dependent parameter that describes the volatility of a substance and thus its driving force for evaporation or sublimation into the gas phase. Depending on the magnitude of the vapor pressure, there are different methods for experimental determination. However, these are usually associated with a corresponding amount of effort and become less accurate as the vapor pressure decreases. For purposes of vapor pressure prediction, algorithms were developed that are usually based on quantitative structure–activity relationships (QSAR). The quantum mechanical (QM) approach followed here applies an alternative, much less empirical strategy, where the change in Gibbs free energy for the transition from the condensed to the gas phase is obtained from conformer ensembles computed for each phase separately. The results of this automatic, so-called CRENSO workflow are compared with experimentally determined vapor pressures for a large set of environmentally relevant compounds. In addition, comparisons are made with the single structure-based COSMO-RS QM approach, linear-free-energy relationships (LFER) as well as results from the SPARC program. We show that our CRENSO workflow is superior to conventional prediction models and provides reliable vapor pressures for liquids and sub-cooled liquids over a wide pressure range.

This work presents the theoretical background to evaluate two-photon absorption (2PA) cross-sections in the framework of simplified time-dependent density functional theory (sTD-DFT). Our new implementation allows the ultrafast evaluation of 2PA cross-sections for large molecules based on a regular DFT ground-state determinant as well as a variant employing our tight-binding sTD-DFT-xTX flavor for very large systems. The method is benchmarked against higher-level calculations for trans-stilbene and typical fluorescent protein chromophores. For eGFP, a quadrupolar chromophore and its branched version, the flavine mono-nucleotide, and the iLOV protein, we compare sTD-DFT 2PA spectra to experimental ones. This includes extension and testing of our all-atom quantum chemistry methodology for the evaluation of 2PA for a system of ∼2000 atoms, providing striking agreement with the experimental spectrum.

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly-linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase-transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase-transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne-linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer-hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations.

Studying the redox behavior of Earth-abundant metal complexes and understanding their reactivity under reducing conditions is of fundamental importance for activating small molecules. We present the electrochemical behavior and reactivity of amine-functionalized indenylmanganese(I) complexes that form the piano-stool complexes MnI(CO)3(IndR) (R = pyrrolidinyl, piperazinyl), which exhibit two cathodic redox waves via cyclic voltammetry (CV). Electrochemical, spectroscopic, and structural comparisons of these complexes with the undecorated indenyl species reveal that the pyrrolidine-substituted tricarbonylmanganese complex MnIndPyrr is the most electron rich due to favorable π donor effects from the amine into the ring system. These results are also strongly supported by DFT computations. Although CV studies show clean redox behavior, reaction outcomes in the presence of common chemical reductants are strongly dependent on the reagents used. Reduction of MnIndPyrr with KC8 in the presence of the encapsulating agent 2,2,2-Crypt forms a rare Mn(0) metalloradical, [K(2,2,2-Crypt)][MnIndPyrr] which was characterized by single crystal X-ray diffraction, EPR spectroscopy, IR spectroscopy, and DFT calculations. Attempts to isolate a doubly reduced Mn(-I) adduct in the presence of 18-crown-6 resulted in indenide anion loss to generate a mixed-valence Mn(-I)/Mn(I) adduct where the two metal centers bind to a single indenyl moiety. This study emphasizes the dramatic differences between observing redox-reversible behavior on the electroanalytical scale and performing preparative scale reduction reactions with alkali metals and encapsulating agent, as these reagents have a profound impact on the reaction outcome.

The adiabatic energy gap between the lowest singlet and triplet excited states ΔEST is a central property of thermally activated delayed fluorescence (TADF) emitters. Since these states are dominated by a charge-transfer character, causing strong orbital-relaxation and environmental effects, an accurate prediction of ΔEST is very challenging, even with modern quantum-chemical excited-state methods. Addressing this major challenge, we present an approach that combines spin-unrestricted (UKS) and restricted open-shell Kohn-Sham (ROKS) self-consistent field calculations with a polarizable-continuum model and range-separated hybrid functionals. Tests on a new representative benchmark set of 27 TADF emitters with accurately known ΔEST values termed STGABS27 reveal a robust and unprecedented performance with a mean absolute deviation of only 0.025 eV (∼0.5 kcal/mol) and few deviations greater than 0.05 eV (∼1 kcal/mol), even in electronically challenging cases. Requiring only two geometry optimizations per molecule at the ROKS/UKS level in a compact double-ζ basis, the approach is computationally efficient and can routinely be applied to molecules with more than 100 atoms.

The high-throughput identification of unknown metabolites in biological samples remains challenging. Most current non-targeted metabolomics studies rely on mass spectrometry, followed by computational methods that rank thousands of candidate structures based on how closely their predicted mass spectra match the experimental mass spectrum of an unknown. We reasoned that the infrared (IR) spectra could be used in an analogous manner and could add orthologous structure discrimination; however, this has never been evaluated on large data sets. Here, we present results of a high-throughput computational method for predicting IR spectra of candidate compounds obtained from the PubChem database. Predicted spectra were ranked based on their similarity to gas-phase experimental IR spectra of test compounds obtained from the NIST. Our computational workflow (IRdentify) consists of a fast semiempirical quantum mechanical method for initial IR spectra prediction, ranking, and triaging, followed by a final IR spectra prediction and ranking using density functional theory. This approach resulted in the correct identification of 47% of 258 test compounds. On average, there were 2152 candidate structures evaluated for each test compound, giving a total of approximately 555,200 candidate structures evaluated. We discuss several variables that influenced the identification accuracy and then demonstrate the potential application of this approach in three areas: (1) combining IR and mass spectra rankings into a single composite rank score, (2) identifying the precursor and fragment ions using cryogenic ion vibrational spectroscopy, and (3) the incorporation of a trimethylsilyl derivatization step to extend the method compatibility to less-volatile compounds. Overall, our results suggest that matching computational with experimental IR spectra is a potentially powerful orthogonal option for adding significant high-throughput chemical structure discrimination when used with other non-targeted chemical structure identification methods.

Attachment of a pair of P-stereogenic mesityl(alkynyl)phosphanyl groups at the 4- and 5-positions of a 9,9-dimethylxanthene framework gave mixtures of the respective rac- and meso-bisphosphanyl diastereoisomers. They slowly epimerized in a thermally induced reaction with Gibbs activation barriers of about 25 kcal mol-1 at room temperature (measured and DFT calculated). The reaction of the meso-mesityl(tert-butylethynyl)phosphanyl derivative with two molar equivalents of Piers' borane [HB(C6 F5 )2 ] led to the formation of the alkylidene-bridged geminal bisphosphane/borane-frustrated Lewis pair system. The compound was obtained enriched (>85 %) in the rac diastereoisomer. With a variety of bifunctional donor substrates, the rac-bis-P/B FLP formed macrocyclic compounds. They were all formally derived from meso-configurated diastereoisomers of the bisphosphanylxanthene backbone.

Primary acyl-phosphines are scarce in the literature. Here we show that the reaction of Ph3 GePCO with the ylide Ph3 PCH2 proceeds to give the species Ph3 PCHC(O)PH(GePh3 ) 1. Deprotonation of 1 with Na[N(SiMe3 )2 ] generates the salt [Na(THF)2 ][Ph3 PCHC(O)P(GePh3 )] 2 which provides subsequent access to the bis-germanylated acylphosphine, Ph3 PCHC(O)P(GePh3 )2 3. Alternatively, treatment of 1 with HCl in dioxane affords the primary acylphosphine Ph3 PCHC(O)PH2 4. Compound 4 is a rare example of an air stable primary acyl-phosphines and the first devoid of a stabilizing heteroatom adjacent to the carbonyl fragment.

Fullerenes and diamondoids are at the core of nanoscience. Comparable monodisperse silicon analogues are scarce. Herein, we report the synthesis of the parent siladodecahedrane, which represents the largest Platonic solid. It shares its pattern of pentagonal faces with the smallest fullerene, C20, and its saturated, H-terminated skeleton with diamondoids. Similar to endofullerenes, the silicon cage encapsulates a chloride ion ([Cl@Si20H20]-); similar to diamondoids, its Si-H termini offer a wealth of opportunities for further functionalization. Mere treatment with chloromethanes leads to the perchlorinated cluster [Cl@Si20Cl20]-. Both compounds were characterized by mass spectrometry, X-ray crystallography, NMR spectroscopy, and quantum-chemical calculations. The experimentally determined 35Cl resonances of the endohedral chloride ions are particularly diagnostic to probe the Cl- → Si20 interaction strength as a function of the different surface substituents, as we have proven by high-level computational analyses.