Nitrogen reduction by the Fe sites of synthetic [Mo3S4Fe] cubes.

Nitrogen (N2) fixation by nature, which is a crucial process for the supply of bio-available forms of nitrogen, is performed by nitrogenase. This enzyme uses a unique transition-metal-sulfur-carbon cluster as its active-site co-factor ([(R-homocitrate)MoFe7S9C], FeMoco)1,2, and the sulfur-surrounded iron (Fe) atoms have been postulated to capture and reduce N2 (refs. 3-6). Although there are a few examples of synthetic counterparts of the FeMoco, metal-sulfur cluster, which have shown binding of N2 (refs. 7-9), the reduction of N2 by any synthetic metal-sulfur cluster or by the extracted form of FeMoco10 has remained elusive, despite nearly 50 years of research. Here we show that the Fe atoms in our synthetic [Mo3S4Fe] cubes11,12 can capture a N2 molecule and catalyse N2 silylation to form N(SiMe3)3 under treatment with excess sodium and trimethylsilyl chloride. These results exemplify the catalytic silylation of N2 by a synthetic metal-sulfur cluster and demonstrate the N2-reduction capability of Fe atoms in a sulfur-rich environment, which is reminiscent of the ability of FeMoco to bind and activate N2.

Development of Novel Immobilized Copper-Ligand Complex for Click Chemistry of Biomolecules.

Copper-catalyzed azide-alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst's utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar.

A systematic mechanistic survey on the reactions between OH radical and CH3OH on ice.

A systematic mechanistic survey was performed for the CH3OH + OH reaction on ice. ONIOM(ωB97X-D/Def2-TZVP:AMOEBA09) calculations suggested a range of binding energies for the CH2OH radical (0.29-0.69 eV) and CH3OH (0.15-0.72 eV) molecule on hexagonal water ice (Ih) and amorphous solid water (ASW). Computed average binding energies of CH2OH radical (0.49 eV) and CH3OH (0.41 eV) are relatively stronger compared to the CH3O radical binding energies (0.32 eV, Sameera et al., J. Phy. Chem. A, 2021, 125, 387-393). Thus, the CH3OH molecule, CH2OH and CH3O radicals can adsorb on ice, where the binding energies follow the order CH2OH > CH3OH > CH3O. The multi-component artificial force-induced reaction (MC-AFIR) method systematically determined the reaction mechanisms for the CH3OH + OH reaction on ice, where two reaction paths, giving rise to CH2OH and CH3O radicals, were confirmed. A range of reaction barriers, employing the ωB97X-D/Def2-TZVP level of theory, was found for each reaction (0.03-0.11 eV for CH2OH radical formation, and 0.03-0.44 eV for CH3O radical formation). Based on the lowest energy reaction paths, we suspect that both reactions operate on ice. The computed data in this study evidence that the nature of the binding site or the reaction site has a significant effect on the computed binding energies or reaction barriers. Thus, the outcomes of the present study will be very useful for the computational astrochemistry community to determine reliable binding energies and reaction barriers on ice.

Palladium-Catalyzed Regioselective and Stereospecific Ring-Opening Cross-Coupling of Aziridines: Experimental and Computational Studies.

Aziridines, i.e., the smallest saturated N-heterocycles, serve as useful building blocks in synthetic organic chemistry. Because of the release of the large ring strain energy accommodated in the small ring, (ca. 27 kcal/mol), aziridines undergo ring-opening reactions with a variety of nucleophiles. Therefore, among the synthetic reactions utilizing aziridines, regioselective ring-opening substitutions of aziridines with nucleophiles, such as heteroatomic nucleophiles (e.g., amines, alcohols, and thiols) and carbonaceous nucleophiles (e.g., carbanions, organometallic reagents, and electron-rich arenes), constitute a useful synthetic methodology to synthesize biologically relevant ß-functionalized alkylamines. However, the regioselection in such traditional ring-opening substitutions of aziridines is highly dependent on the substrate combination, and stereochemical control is challenging to achieve, especially in the case of Lewis acid-promoted variants. Therefore, the development of robust catalytic ring-opening functionalization methods that enable precise prediction of regioselectivity and stereochemistry is desirable. In this direction, our group focused on the highly regioselective and stereospecific nature of the stoichiometric oxidative addition elementary step of 2-substituted aziridines into Pd(0) complexes in an SN2 fashion. In conjunction with the recent advancements in transition-metal-catalyzed cross-coupling reactions of alkyl pseudohalides containing a C(sp3)-Q (Q = O, N, S, etc.) bond, aziridines can be used as nonclassical alkyl pseudohalides in regioselective and stereospecific cross-couplings.In this Account, starting from the background of transition-metal-catalyzed ring-opening functionalization of aziridines, our contributions to the palladium-catalyzed regioselective and stereoinvertive cross-couplings of aziridines with organoboron reagents to form C(sp3)-C, C(sp3)-B, and C(sp3)-Si bonds have been compiled. The developed methods allow the syntheses of medicinally important amine compounds, e.g., enantioenriched ß-phenethylamines, ß-amino acids, and their boron and silyl surrogates, from readily available enantiopure aziridine substrates. Notably, the regioselectivity of the ring opening can be switched by appropriate selection of the catalyst (i.e., Pd/NHC vs Pd/PR3 systems). Computational studies rationalized the detailed mechanisms of the full catalytic cycle and the regioselectivity and stereospecificity of the reactions. The computational results suggested that the interactions operating between the Pd catalyst and aziridine substrate play important roles in determining the regioselection of the aziridine ring-opening event (i.e., oxidative addition). Also, the computational results rationalized the role of water molecules in promoting the transmetalation step through the formation of a Pd-hydroxide active intermediate. This Account evidences the benefits of synergistic collaborations between experimental and computational methods in developing novel transition-metal-catalyzed cross-coupling reactions.

CH3O Radical Binding on Hexagonal Water Ice and Amorphous Solid Water.

Binding energies of the CH3O radical on hexagonal water ice (Ih) and amorphous solid water (ASW) were calculated using the ONIOM(QM:MM) method. A range of binding energies is found (0.10-0.50 eV), and the average binding energy is 0.32 eV. The CH3O radical binding on the ASW surfaces is stronger than on the Ih surfaces. The computed binding energies from the ONIOM(wB97X-D/def2-TZVP:AMBER) and wB97X-D/def2-TZVP methods agree quite well. Therefore, the ONIOM(QM:MM) method is expected to give accurate binding energies at a low computational cost. Binding energies from the ONIOM(wB97X-D/def2-TZVP:AMBER) and ONIOM(wB97X-D/def2-TZVP:AMOEBA09) methods differ noticeably, indicating that the choice of force field matters. According to the energy decomposition analysis, the electrostatic interactions and Pauli repulsions between the CH3O radical and ice play a crucial role in the binding energy. This study gives quantitative insights into the CH3O radical binding on interstellar ices.

Siloxy Esters as Traceless Activators of Carboxylic Acids: Boron-Catalyzed Chemoselective Asymmetric Aldol Reaction*.

The catalytic asymmetric aldol reaction is among the most useful reactions in organic synthesis. Despite the existence of many prominent reports, however, the late-stage, chemoselective, catalytic, asymmetric aldol reaction of multifunctional substrates is still difficult to achieve. Herein, we identified that in situ pre-conversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic, asymmetric aldol reaction applicable to multifunctional substrates. Combining experimental and computational studies rationalized the reaction mechanism and led to the proposal of Si/B enediolates as the active species. The silyl ester formation facilitated both enolization and catalyst turnover by acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

Synthesis of Dinuclear Mo-Fe Hydride Complexes and Catalytic Silylation of N2.

Two transition-metal atoms bridged by hydrides may represent a useful structural motif for N2 activation by molecular complexes and the enzyme active site. In this study, dinuclear MoIV -FeII complexes with bridging hydrides, CpR Mo(PMe3 )(H)(µ-H)3 FeCp* (2 a; CpR =Cp*=C5 Me5 , 2 b; CpR =C5 Me4 H), were synthesized via deprotonation of CpR Mo(PMe3 )H5 (1 a; CpR =Cp*, 1 b; CpR =C5 Me4 H) by Cp*FeN(SiMe3 )2 , and they were characterized by spectroscopy and crystallography. These Mo-Fe complexes reveal the shortest Mo-Fe distances ever reported (2.4005(3) Šfor 2 a and 2.3952(3) Šfor 2 b), and the Mo-Fe interactions were analyzed by computational studies. Removal of the terminal Mo-H hydride in 2 a-2 b by [Ph3 C]+ in THF led to the formation of cationic THF adducts [CpR Mo(PMe3 )(THF)(µ-H)3 FeCp*]+ (3 a; CpR =Cp*, 3 b; CpR =C5 Me4 H). Further reaction of 3 a with LiPPh2 gave rise to a phosphido-bridged complex Cp*Mo(PMe3 )(µ-H)(µ-PPh2 )FeCp* (4). A series of Mo-Fe complexes were subjected to catalytic silylation of N2 in the presence of Na and Me3 SiCl, furnishing up to 129±20 equiv of N(SiMe3 )3 per molecule of 2 b. Mechanism of the catalytic cycle was analyzed by DFT calculations.

Bright Luminescent Platinum(II)-Biaryl Emitters Synthesized Without Air-Sensitive Reagents.

Transition-metal complexes bearing biaryl-2,2'-diyl ligands tend to show intense luminescence. However, difficulties in synthesis have prevented their further functionalization and practical applications. Herein, a series of platinum(II) complexes bearing biaryl-2,2'-diyl ligands, which have never been prepared in air, were synthesized through transmetalation and successive cyclometalation of biarylboronic acids. This approach does not require any air- or moisture-sensitive reagents and features a simple synthesis even in air. The resulting (Et4 N)2 [Pt(m,n-F2 bph)(CN)2 ] (m,n-F2 bph=m,n-difluorobiphenyl-2,2'-diyl) complexes exhibit intense green emissions with high quantum efficiencies of up to 0.80 at 298 K. The emission spectral fitting and variable-temperature emission lifetime measurements indicate that the high quantum efficiency was achieved because of the tight packing structure and strong σ-donating ability of bph.

Robust Triplatinum Redox-Chromophore for a Post-Synthetic Color-Tunable Electrochromic System.

An electrochromic system showing ease of color tunability has been constructed using a triple-decker PtII complex [Pt3 (µ3 -pydt)2 (bpy)3 ]2+ (H2 pydt=2,6-pyridinedithiol, bpy=2,2'-bipyridine). The divalent complex undergoes electrochemically quasi-reversible two-electron transfer coupled with the coordination/dissociation of axial ligands, forming higher valent Pt(+2.67) species [Pt3 X2 (µ3 -pydt)2 (bpy)3 ]2+ (X=Cl- , Br- , and SCN- ). These higher valent species exhibit characteristic colors ranging from red to cyan depending on the counter anion X- of the electrolyte. The triple-decker structure provides a novel multicolor electrochromic system with favorable stability and reversibility. Theoretical calculations indicate that the colors of the Pt(+2.67) species are tunable by the trans influence of the axial ligand X- . This novel strategy of post-synthetic color-tuning using triplatinum systems should enable the facile preparation of colorful electrochromic devices without any complicated procedures, which may find application in flexible displays, optical devices, and sensors.

Asymmetric Synthesis of ß2 -Aryl Amino Acids through Pd-Catalyzed Enantiospecific and Regioselective Ring-Opening Suzuki-Miyaura Arylation of Aziridine-2-carboxylates.

A Pd-catalyzed enantiospecific and regioselective ring-opening Suzuki-Miyaura arylation of aziridine-2-carboxylates was developed. The cross-coupling allows for the asymmetric preparation of enantioenriched ß2 -aryl amino acids, starting from commercially available enantiopure d- and l-serine esters. The mechanism and selectivity of the reaction was rationalized based on computational models.

Cubane-Type [Mo3 S4 M] Clusters with First-Row Groups†4-10 Transition-Metal Halides Supported by C5 Me5 Ligands on Molybdenum.

A synthetic protocol was developed for a series of cubane-type [Mo3 S4 M] clusters that incorporate halides of first-row transition metals (M) from Groups 4-10. This protocol is based on the anionic cluster platform [Cp*3 Mo3 S4 ]- ([1]- ; Cp*=η5 -C5 Me5 ), which crystallizes when K(18-crown-6) is used as the counter cation. Treatment of in situ-generated [1]- with such transition-metal halides led to the formation of [Mo3 S4 M] clusters, in which the M/halide ratio gradually changes from 1:2 to 1:1.5 and to 1:1, when moving from early to late transition metals. This trend suggests a tendency for early transition metals to tolerate higher oxidation states and adopt larger ionic radii relative to late transition metals. The properties of the [Mo3 S4 Fe] cluster 6 a were investigated in detail by using 57 Fe Mössbauer spectroscopy and computational methods.

Phosphorescence Properties of Discrete Platinum(II) Complex Anions Bearing N-Heterocyclic Carbenes in the Solid State.

The synthesis, crystal structures, and photophysical properties of four anionic platinum complexes bearing N-heterocyclic carbenes (NHCs), n-Bu4N[Pt(CN)2(NHC)] (H2NHC+ = 1-methyl-3-phenyl-1 H-imidazolium (1), 1-methyl-3-phenyl-1 H-benzimidazolium (2), 1-methyl-3-(naphthalen-2-yl)-1 H-imidazolium (3), 1-methyl-3-(naphthalen-1-yl)-1 H-imidazolium (4)), are reported. The tetra- n-butylammonium salts afforded discrete Pt(II) complexes surrounded by the bulky cations in the crystalline states with no Pt-Pt, π-π, or solute-solvent interactions. As a result, the crystals exhibited strong phosphorescence with quantum yields of 0.24-0.72 at 298 K. The three isomeric complexes 2-4 with π-extended structures of 1 exhibited luminescence with different colors depending on the π-extension site. These complexes in a discrete and restricted space enabled the comparative investigation of the luminescent states and regioselective benzannulation effect using computational methods and luminescence spectroscopy. Blue-emissive 1 and 2 exhibited lifetime changes at temperatures of 77-298 K, suggesting the influence of dark states located 2000-3000 cm-1 above the emissive state. In contrast, yellow- and orange-emissive 3 and 4 showed no thermal deactivation effect at ambient temperature. The temperature dependence of the emission lifetimes in the low-temperature region of 4-77 K showed that blue-emissive 1 and 2 had a relatively large zero-field splittings (ZFSs) of 35 and 28 cm-1, respectively, indicating the significant contribution of triplet metal-to-ligand charge transfer character to the 3π-π* emission. On the other hand, the ZFS of 4 was less than 2 cm-1, suggesting purer 3π-π* character.

Solvent-Free Thermal Synthesis of Luminescent Dinuclear Cu(I) Complexes with Triarylphosphines.

Luminescent [Cu2I2(pyrpy)2(PR3)2] complexes (pyrpy = 4-pyrrolidinopyridine; PR3 = triphenylphosphine (1), tri- m-tolylphosphine (2), tri- p-tolylphosphine (3)) were prepared by solution reactions and a rarely reported solvent-free thermal method. X-ray structure analyses reveal that complexes composed of dinuclear {Cu2I2} cores surrounded by two PR3 and two pyrpy ligands were formed. Although the melting point of pyrpy is the lowest among the organic units used in this study, the temperature required to form the luminescent dinuclear complex, prepared by the thermal synthesis method, depended strongly on the PR3 moiety. Two of the three complexes (1 and 3) were successfully prepared by the solvent-free thermal method. Complexes 1-3 exhibited blue emissions at around 450 nm with moderately high quantum yields (Φ) of 0.24, 0.31, and 0.51, respectively. Emission-lifetime measurements and time-dependent density functional theory (TD-DFT) calculations suggest thermally activated delayed fluorescence (TADF) in each complex. This solvent-free thermal synthesis of TADF materials represents a promising method for the preparation of luminescent layers directly onto substrates of thin-layer electronic devices, such as organic light-emitting diodes.

Expanding the Range of Force Fields Available for ONIOM Calculations: The SICTWO Interface.

The ONIOM scheme is one of the most popular QM/MM approaches, but its extended application has been so far hindered by the limited availability of force fields in most practical implementations. This paper describes a simple software code to overcome this limitation, and its application to three representative chemical problems. The "Shell Interface for Combining Tinker With ONIOM" (SICTWO) program gives access to all force fields available in the Tinker molecular mechanics program from a Gaussian09 or Gaussian16 calculation. The first application presented is the geometry optimization of dithienobicyclo-[4.4.1]-undeca-3,8-diene-11-one ethylene glycol ketal. A variety of force fields were tested for the MM part, and the molecular structure using the ONIOM(B3LYP:OPLS-AA) method shows good agreement with the experimental results. The second problem is related with enantioselectivity of the vanadium-catalyzed asymmetric oxidation of 1,2-bis( tert-butyl)-disulfide. ONIOM(B3LYP:MM3) results, obtained with SICTWO, are consistent with those of a previous IMOMM(B3LYP:MM3) study. In the third application, we have combined AMOEBA09 polarizable force field with ONIOM to study a water molecule binding on water ice. Calculated ONIOM(ωB97X-D:AMOEBA09) binding energies are consistent with the ωB97X-D results. These studies show SICTWO as an easy-to-use tool that can further expand the use of the multiscale ONIOM method within computational chemistry and computational biology.

DFT and AFIR Study on the Mechanism and the Origin of Enantioselectivity in Iron-Catalyzed Cross-Coupling Reactions.

The mechanism of the full catalytic cycle for Fe-chiral-bisphosphine-catalyzed cross-coupling reaction between alkyl halides and Grignard reagents (Nakamura and co-workers, J. Am. Chem. Soc. 2015, 137, 7128) was rationalized by using density functional theory (DFT) and multicomponent artificial force-induced reaction (MC-AFIR) methods. The computed mechanism consists of (a) C-Cl activation, (b) transmetalation, (c) C-Fe bond formation, and (d) C-C bond formation through reductive elimination. Our survey on the prereactant complexes suggested that formation of FeII(BenzP*)Ph2 and FeI(BenzP*)Ph complexes are thermodynamically feasible. FeI(BenzP*)Cl complex is the active intermediate for C-Cl activation. FeII(BenzP*)Ph2 complex can be formed if the concentration of Grignard reagent is high. However, it leads to biphenyl (byproduct) instead of the cross-coupling product. This explains why slow addition of Grignard reagent is critical for the cross-coupling reaction. The MC-AFIR method was used for systematic determination of transition states for C-Fe bond formation and C-C bond formation starting from the key intermediate FeII(BenzP*)PhCl. According to our detailed analysis, C-C bond formation is the selectivity-determining step. The computed enantiomeric ratio of 95:5 is in good agreement with the experimental ratio (90:10). Energy decomposition analysis suggested that the origin of the enantioselectivity is the deformation of Ph-ligand in Fe-complex, which is induced by the bulky tert-butyl group of BenzP* ligand. Our study provides important mechanistic insights for the cross-coupling reaction between alkyl halides and Grignard reagents and guides the design of efficient Fe-based catalysts for cross-coupling reactions.

Functional-Group-Tolerant, Silver-Catalyzed N-N Bond Formation by Nitrene Transfer to Amines.

Silver(I) promotes the highly chemoselective N-amidation of tertiary amines under catalytic conditions to form aminimides by nitrene transfer from PhI═NTs. Remarkably, this transformation proceeds in a selective manner in the presence of olefins and other functional groups without formation of the commonly observed aziridines or C-H insertion products. The methodology can be applied not only to rather simple tertiary amines but also to complex natural molecules such as brucine or quinine, where the products derived from N-N bond formation were exclusively formed. Theoretical mechanistic studies have shown that this selective N-amidation reaction proceeds through triplet silver nitrenes.

Computational Catalysis Using the Artificial Force Induced Reaction Method.

The artificial force induced reaction (AFIR) method in the global reaction route mapping (GRRM) strategy is an automatic approach to explore all important reaction paths of complex reactions. Most traditional methods in computational catalysis require guess reaction paths. On the other hand, the AFIR approach locates local minima (LMs) and transition states (TSs) of reaction paths without a guess, and therefore finds unanticipated as well as anticipated reaction paths. The AFIR method has been applied for multicomponent organic reactions, such as the aldol reaction, Passerini reaction, Biginelli reaction, and phase-transfer catalysis. In the presence of several reactants, many equilibrium structures are possible, leading to a number of reaction pathways. The AFIR method in the GRRM strategy determines all of the important equilibrium structures and subsequent reaction paths systematically. As the AFIR search is fully automatic, exhaustive trial-and-error and guess-and-check processes by the user can be eliminated. At the same time, the AFIR search is systematic, and therefore a more accurate and comprehensive description of the reaction mechanism can be determined. The AFIR method has been used for the study of full catalytic cycles and reaction steps in transition metal catalysis, such as cobalt-catalyzed hydroformylation and iron-catalyzed carbon-carbon bond formation reactions in aqueous media. Some AFIR applications have targeted the selectivity-determining step of transition-metal-catalyzed asymmetric reactions, including stereoselective water-tolerant lanthanide Lewis acid-catalyzed Mukaiyama aldol reactions. In terms of establishing the selectivity of a reaction, systematic sampling of the transition states is critical. In this direction, AFIR is very useful for performing a systematic and automatic determination of TSs. In the presence of a comprehensive description of the transition states, the selectivity of the reaction can be calculated more accurately. For relatively large molecular systems, the computational cost of AFIR searches can be reduced by using the ONIOM(QM:QM) or ONIOM(QM:MM) methods. In common practice, density functional theory (DFT) with a relatively small basis set is used for the high-level calculation, while a semiempirical approach or a force field description is used for the low-level calculation. After approximate LMs and TSs are determined, standard computational methods (e.g., DFT with a large basis set) are used for the full molecular system to determine the true LMs and TSs and to rationalize the reaction mechanism and selectivity of the catalytic reaction. The examples in this Account evidence that the AFIR method is a powerful approach for accurate prediction of the reaction mechanisms and selectivities of complex catalytic reactions. Therefore, the AFIR approach in the GRRM strategy is very useful for computational catalysis.

Luminescent Re(I) Carbonyl Complexes as Trackable PhotoCORMs for CO delivery to Cellular Targets.

A family of Re(I) carbonyl complexes of general formula [ReX(CO)3(phen)]0/1+ (where X = Cl-, CF3SO3-, MeCN, PPh3, and methylimidazole) derived from 1,10-phenanthroline (phen) exhibits variable emission characteristics depending on the presence of the sixth ancillary ligand/group (X). All complexes but with X = MeCN exhibit moderate CO release upon irradiation with low-power UV light and are indefinitely stable in anaerobic/aerobic environment in solution as well as in solid state when kept under dark condition. These CO donors liberate three, one, or no CO depending on the nature of sixth ligand upon illumination as studied with the aid of time-dependent IR spectroscopy. Results of excited-state density functional theory (DFT) and time-dependent DFT calculations provided insight into the origin of the emission characteristics of these complexes. The luminescent rheinum(I) photoCORMs uniformly displayed efficient cellular internalization by the human breast adenocarcinoma cells, MDA-MB-231, while the complex with PPh3 as ancillary ligand showed moderate nuclear localization in addition to the cytosolic distribution. These species hold significant promise as theranostic photoCORMs (photoinduced CO releasing molecules), where the entry of the pro-drug can be tracked within the cellular matrices.