Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

We report the selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold using a Br/Mg-exchange, as well as regioselective magnesiations and zincations with TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl), followed by trapping reactions with various electrophiles. In addition, we report a fragmentation of the pyrazole ring, giving access to push–pull dyes with a proaromatic (1,3-dihydro-2H-imidazol-2-ylidene)malononitrile core. These functionalization methods were used in the synthesis of an isostere of the indolyl drug pruvanserin. Comparative assays between the original drug and the isostere showed that a substitution of the indole ring with a 1H-imidazo[1,2-b]pyrazole results in a significantly improved solubility in aqueous media.

A methodology for the selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold has been developed and used in the synthesis of novel push–pull dyes and a non-classical isostere of the indolyl drug pruvanserin.     

Activating intramolecular singlet exciton fission by altering π-bridge flexibility in perylene diimide trimers for organic solar cells

In this study, two analogous perylene diimide (PDI) trimers, whose structures show rotatable single bond π-bridge connection (twisted) vs. rigid/fused π-bridge connection (planar), were synthesized and investigated. We show via time resolved spectroscopic measurements how the π-bridge connections in A–π–D–π–A–π–D–π–A multichromophoric PDI systems strongly affect the triplet yield and triplet formation rate. In the planar compound, with stronger intramolecular charge transfer (ICT) character, triplet formation occurs via conventional intersystem crossing. However, clear evidence of efficient and fast intramolecular singlet exciton fission (iSEF) is observed in the twisted trimer compound with weaker ICT character. Multiexciton triplet generation and separation occur in the twisted (flexible-bridged) PDI trimer, where weak coupling among the units is observed as a result of the degenerate double triplet and quintet states, obtained by quantum chemical calculations. The high triplet yield and fast iSEF observed in the twisted compound are due not only to enthalpic viability but also to the significant entropic gain allowed by its trimeric structure. Our results represent a significant step forward in structure–property understanding, and may direct the design of new efficient iSEF materials.

We show via time resolved spectroscopy that triplet formation proceeds via intersystem crossing in a rigid-bridged perylene diimide trimer and via efficient and fast intramolecular singlet exciton fission in the analogous flexible-bridged trimer.     

New Cy5 photosensitizers for cancer phototherapy: a low singlet–triplet gap provides high quantum yield of singlet oxygen

Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are produced via singlet–triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer. The introduction of an electron-withdrawing group at the meso-position of TCy5 could dramatically reduce the singlet–triplet energy gap (ΔE_st) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τ_ISC = 1.7 ps), prolong the lifetime of the triplet state (τ_T = 319 μs) and improve singlet oxygen (¹O₂) quantum yield to as high as 99%, a value much higher than those of most reported triplet PSs. Further in vitro and in vivo experiments have shown that TCy5-CHO, with its efficient ¹O₂ generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy.

The electron-withdrawing group at the meso-position of Thio-Cy5 could dramatically reduce the singlet–triplet energy gap, and speed up the intersystem crossing process.     

Electron spin polarization generated by transport of singlet and quintet multiexcitons to spin-correlated triplet pairs during singlet fissions

Singlet fission (SF) is expected to exceed the Shockley–Queisser theoretical limit of efficiency of organic solar cells. Transport of spin-entanglement in the triplet–triplet pair state via one singlet exciton is a promising phenomenon for several energy conversion applications including quantum information science. However, direct observation of electron spin polarization by transport of entangled spin-states has not been presented. In this study, time-resolved electron paramagnetic resonance has been utilized to observe the transportation of singlet and quintet characters generating correlated triplet–triplet (T + T) exciton-pair states by probing the electron spin polarization (ESP) generated in thin films of 6,13-bis(triisopropylsilylethynyl)pentacene. We have clearly demonstrated that the ESP detected at the resonance field positions of individual triplet excitons is dependent on the morphology and on the detection delay time after laser flash to cause SF. ESP was clearly explained by quantum superposition of singlet–triplet–quintet wavefunctions via picosecond triplet-exciton dissociation as the electron spin polarization transfer from strongly exchange-coupled singlet and quintet TT states to weakly-coupled spin-correlated triplet pair states. Although the coherent superposition of spin eigenstates was not directly detected, the present interpretation of the spin correlation of the separated T + T exciton pair may pave new avenues not only for elucidating the vibronic role in the de-coupling between two excitons but also for scalable quantum information processing using quick T + T dissociation via one-photon excitation.

Singlet fission (SF) is expected to exceed the Shockley–Queisser theoretical limit of efficiency of organic solar cells.     

Dye-sensitized solar cells based on Fe N-heterocyclic carbene photosensitizers with improved rod-like push-pull functionality

A new generation of octahedral iron(ii)–N-heterocyclic carbene (NHC) complexes, employing different tridentate C^N^C ligands, has been designed and synthesized as earth-abundant photosensitizers for dye sensitized solar cells (DSSCs) and related solar energy conversion applications. This work introduces a linearly aligned push–pull design principle that reaches from the ligand having nitrogen-based electron donors, over the Fe(ii) centre, to the ligand having an electron withdrawing carboxylic acid anchor group. A combination of spectroscopy, electrochemistry, and quantum chemical calculations demonstrate the improved molecular excited state properties in terms of a broader absorption spectrum compared to the reference complex, as well as directional charge-transfer displacement of the lowest excited state towards the semiconductor substrate in accordance with the push–pull design. Prototype DSSCs based on one of the new Fe NHC photosensitizers demonstrate a power conversion efficiency exceeding 1% already for a basic DSSC set-up using only the I⁻/I₃⁻ redox mediator and standard operating conditions, outcompeting the corresponding DSSC based on the homoleptic reference complex. Transient photovoltage measurements confirmed that adding the co-sensitizer chenodeoxycholic acid helped in improving the efficiency by increasing the electron lifetime in TiO₂. Time-resolved spectroscopy revealed spectral signatures for successful ultrafast (<100 fs) interfacial electron injection from the heteroleptic dyes to TiO₂. However, an ultrafast recombination process results in undesirable fast charge recombination from TiO₂ back to the oxidized dye, leaving only 5–10% of the initially excited dyes available to contribute to a current in the DSSC. On slower timescales, time-resolved spectroscopy also found that the recombination dynamics (longer than 40 μs) were significantly slower than the regeneration of the oxidized dye by the redox mediator (6–8 μs). Therefore it is the ultrafast recombination down to fs-timescales, between the oxidized dye and the injected electron, that remains as one of the main bottlenecks to be targeted for achieving further improved solar energy conversion efficiencies in future work.

Iron-based photosensitizers for dye-sensitized solar cells with a rod-like push–pull design. Solar cell performance was limited by ultrafast (sub-ps) recombination, but yielded better performance than the homoleptic parent photosensitizer.     

Anion-enhanced excited state charge separation in a spiro-locked N-heterocycle-fused push-pull zinc porphyrin

A new type of push–pull charge transfer complex, viz., a spiro-locked N-heterocycle-fused zinc porphyrin, ZnP-SQ, is shown to undergo excited state charge separation, which is enhanced by axial F⁻ binding to the Zn center. In this push–pull design, the spiro-quinone group acts as a ‘lock’ promoting charge transfer interactions by constraining mutual coplanarity of the meso-phenol-substituted electron-rich Zn(ii) porphyrin and an electron deficient N-heterocycle, as revealed by electrochemical and computational studies. Spectroelectrochemical studies have been used to identify the spectra of charge separated states, and charge separation upon photoexcitation of ZnP has been unequivocally established by using transient absorption spectroscopic techniques covering wide spatial and temporal regions. Further, global target analysis of the transient data using GloTarAn software is used to obtain the lifetimes of different photochemical events and reveal that fluoride anion complexation stabilizes the charge separated state to an appreciable extent.

A new type of push–pull charge transfer complex, viz., a spiro-locked N-heterocycle-fused zinc porphyrin, ZnP-SQ, is shown to undergo excited state charge separation, which is enhanced by axial F⁻ binding to the Zn center.     

The Morita–Baylis–Hillman reaction for non-electron-deficient olefins enabled by photoredox catalysis

A strategy for overcoming the limitation of the Morita–Baylis–Hillman (MBH) reaction, which is only applicable to electron-deficient olefins, has been achieved via visible-light induced photoredox catalysis in this report. A series of non-electron-deficient olefins underwent the MBH reaction smoothly via a novel photoredox-quinuclidine dual catalysis. The in situ formed key β-quinuclidinium radical intermediates, derived from the addition of olefins with quinuclidinium radical cations, are used to enable the MBH reaction of non-electron-deficient olefins. On the basis of previous reports, a plausible mechanism is suggested. Mechanistic studies, such as radical probe experiments and density functional theory (DFT) calculations, were also conducted to support our proposed reaction pathways.

A strategy for overcoming the limitation of the Morita–Baylis–Hillman (MBH) reaction, which is only applicable to electron-deficient olefins, has been achieved via visible-light induced photoredox catalysis in this report.     

Understanding the mechanism of direct visible-light-activated [2 + 2] cycloadditions mediated by Rh and Ir photocatalysts: combined computational and spectroscopic studies

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques. Experimental observations show that the Rh-based photocatalyst produces excellent yield and enantioselectivity whereas the Ir-photocatalyst yields racemates. Two different mechanistic features were found to compete with each other, namely the direct photoactivation of the catalyst–substrate complex and outer-sphere triplet energy transfer. Our integrated analysis suggests that the direct photocatalysis is the inner working of the Rh-catalyzed reaction, whereas the Ir catalyst serves as a triplet sensitizer that activates cycloaddition via an outer-sphere triplet excited state energy transfer mechanism.

The mechanism of [2 + 2] cycloadditions activated by visible light and catalyzed by bis-cyclometalated Rh(iii) and Ir(iii) photocatalysts was investigated, combining density functional theory calculations and spectroscopic techniques.     

Achieving flexible large-scale reactivity tuning by controlling the phase,thickness and support of two-dimensional ZnO

Tuning surface reactivity of catalysts is an effective strategy to enhance catalytic activity towards a chemical reaction. Traditional reactivity tuning usually relies on a change of the catalyst composition, especially when large-scale tuning is desired. Here, based on density functional theory calculations, we provide a strategy for flexible large-scale tuning of surface reactivity, i.e. from a few tenths of electronvolts (eV) to multiple eV, merely through manipulating the phase, thickness, and support of two-dimensional (2D) ZnO films. 2D ZnO films have three typical phases, i.e. graphene, wurtzite, and body-centered-tetragonal structures, whose intrinsic stability strongly depends on the thickness and/or the chemical nature of the support. We show that the adsorption energy of hydrogen differs by up to 3 eV on these three phases. For the same phase, varying the film thickness and/or support can lead to a few tenths of eV to 2 eV tuning of surface reactivity. We further demonstrate that flexible large-scale tuning of surface reactivity has a profound impact on the reaction kinetics, including breaking the Brønsted–Evans–Polanyi relationship.

Flexible large-scale reactivity tuning is achieved by manipulating the phase, thickness and support of two-dimensional ZnO, and a broken scaling relationship between adsorption and barrier is found via phase and termination engineering.     

Ultrafast and long-time excited state kinetics of an NIR-emissive vanadium(iii) complex II. Elucidating triplet-to-singlet excited-state dynamics

We report the non-adiabatic dynamics of V^IIICl₃(ddpd), a complex based on the Earth-abundant first-row transition metal vanadium with a d² electronic configuration which is able to emit phosphorescence in solution in the near-infrared spectral region. Trajectory surface-hopping dynamics based on linear vibronic coupling potentials obtained with CASSCF provide molecular-level insights into the intersystem crossing from triplet to singlet metal-centered states. While the majority of the singlet population undergoes back-intersystem crossing to the triplet manifold, 1–2% remains stable during the 10 ps simulation time, enabling the phosphorescence described in Dorn et al. Chem. Sci., 2021, DOI: 10.1039/D1SC02137K. Competing with intersystem crossing, two different relaxation channels via internal conversion through the triplet manifold occur. The nuclear motion that drives the dynamics through the different electronic states corresponds mainly to the increase of all metal–ligand bond distances as well as the decrease of the angles of trans-coordinated ligand atoms. Both motions lead to a decrease in the ligand-field splitting, which stabilizes the interconfigurational excited states populated during the dynamics. Analysis of the electronic character of the states reveals that increasing and stabilizing the singlet population, which in turn can result in enhanced phosphorescence, could be accomplished by further increasing the ligand-field strength.

The ultrafast triplet-to-singlet mechanism, responsible for the photoluminescence of the open-shell V^IIICl₃(ddpd) complex – based on Earth-abundant vanadium – is unraveled using non-adiabatic dynamics in full dimensionality.     

Me3SiSiMe2(OnBu): a disilane reagent for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement

Herein, a readily available disilane Me₃SiSiMe₂(OⁿBu) has been developed for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement. This protocol enables the incorporation of a silylene into different starting materials, including acrylamides, alkene-tethered 2-(2-iodophenyl)-1H-indoles, and 2-iodobiaryls, via the cleavage of Si–Si, Si–C, and Si–O bonds, leading to the formation of spirobenzosiloles, fused benzosiloles, and π-conjugated dibenzosiloles in moderate to good yields. Preliminary mechanistic studies indicate that this transformation is realized by successive palladium-catalyzed bis-silylation and Brook- and retro-Brook-type rearrangement of silane-tethered silanols.

A readily available disilane Me₃SiSiMe₂(OⁿBu) as a silylene source has been developed for the synthesis of diverse silacycles via Brook- and retro-Brook-type rearrangement.     

Docking rings in a solid: reversible assembling of pseudorotaxanes inside a zirconium metal–organic framework

An unprecedented zirconium metal–organic framework featuring a T-shaped benzimidazole strut was constructed and employed as a sponge-like material for selective absorption of macrocyclic guests. The neutral benzimidazole domain of the as-synthesized framework can be readily protonated and fully converted to benzimidazolium. Mechanical threading of [24]crown-8 ether wheels onto recognition sites to form pseudorotaxanes was evidenced by solution nuclear magnetic resonance, solid-state fluorescence, and infrared spectroscopy. Selective absorption of [24]crown-8 ether rather than its dibenzo counterpart was also observed. Further study reveals that this binding process is reversible and acid–base switchable. The success of docking macrocyclic guests in crystals via host–guest interactions provides an alternative route to complex functional materials with interpenetrated structures.

A T-shaped ligand was designed as struts for building a zirconium metal–organic framework. Acid–base switchable docking and releasing a 24-membered crown ether inside crystals was successfully accomplished via post-synthetic modification.     

Low power threshold photochemical upconversion using a zirconium(iv) LMCT photosensitizer

The current investigation demonstrates highly efficient photochemical upconversion (UC) where a long-lived Zr(iv) ligand-to-metal charge transfer (LMCT) complex serves as a triplet photosensitizer in concert with well-established 9,10-diphenylanthracene (DPA) along with newly conceived DPA–carbazole based acceptors/annihilators in THF solutions. The initial dynamic triplet–triplet energy transfer (TTET) processes (ΔG ∼ −0.19 eV) featured very large Stern–Volmer quenching constants (K_SV) approaching or achieving 10⁵ M⁻¹ with bimolecular rate constants between 2 and 3 × 10⁸ M⁻¹ s⁻¹ as ascertained using static and transient spectroscopic techniques. Both the TTET and subsequent triplet–triplet annihilation (TTA) processes were verified and throughly investigated using transient absorption spectroscopy. The Stern–Volmer metrics support 95% quenching of the Zr(iv) photosensitizer using modest concentrations (0.25 mM) of the various acceptor/annihilators, where no aggregation took place between any of the chromophores in THF. Each of the upconverting formulations operated with continuous-wave linear incident power dependence (λ_ex = 514.5 nm) down to ultralow excitation power densities under optimized experimental conditions. Impressive record-setting η_UC values ranging from 31.7% to 42.7% were achieved under excitation conditions (13 mW cm⁻²) below that of solar flux integrated across the Zr(iv) photosensitizer''s absorption band (26.7 mW cm⁻²). This study illustrates the importance of supporting the continued development and discovery of molecular-based triplet photosensitizers based on earth-abundant metals.

The LMCT photosensitizer Zr(^MesPDP^Ph)₂ paired with DPA-based acceptors enabled low power threshold photochemical upconversion with record-setting quantum efficiencies.     

An economical approach for peptide synthesis via regioselective C–N bond cleavage of lactams

An economical, solvent-free, and metal-free method for peptide synthesis via C–N bond cleavage using lactams has been developed. The method not only eliminates the need for condensation agents and their auxiliaries, which are essential for conventional peptide synthesis, but also exhibits high atom economy. The reaction is versatile because it can tolerate side chains bearing a range of functional groups, affording up to >99% yields of the corresponding peptides without racemisation or polymerisation. Moreover, the developed strategy enables peptide segment coupling, providing access to a hexapeptide that occurs as a repeat sequence in spider silk proteins.

An economical, solvent-free, and metal-free method for peptide synthesis via C–N bond cleavage using lactams has been developed.     

Linking metal–organic cages pairwise as a design approach for assembling multivariate crystalline materials

Using metal–organic cages (MOCs) as preformed supermolecular building-blocks (SBBs) is a powerful strategy to design functional metal–organic frameworks (MOFs) with control over the pore architecture and connectivity. However, introducing chemical complexity into the network via this route is limited as most methodologies focus on only one type of MOC as the building-block. Herein we present the pairwise linking of MOCs as a design approach to introduce defined chemical complexity into porous materials. Our methodology exploits preferential Rh-aniline coordination and stoichiometric control to rationally link Cu₄L₄ and Rh₄L₄ MOCs into chemically complex, yet extremely well-defined crystalline solids. This strategy is expected to open up significant new possibilities to design bespoke multi-functional materials with atomistic control over the location and ordering of chemical functionalities.

A new strategy to design atomically precise multivariate metal–organic frameworks is presented. This is achieved by linking two preformed metal–organic cages via a precisely tuned Rh–aniline interaction.     

Multicomponent syntheses of 5- and 6-membered aromatic heterocycles using group 4–8 transition metal catalysts

In this Perspective, we discuss recent syntheses of 5- and 6-membered aromatic heterocycles via multicomponent reactions (MCRs) that are catalyzed by group 4–8 transition metals. These MCRs can be categorized based on the substrate components used to generate the cyclized product, as well as on common mechanistic features between the catalyst systems. These particular groupings are intended to highlight mechanistic and strategic similarities between otherwise disparate transition metals and to encourage future work exploring related systems with otherwise-overlooked elements. Importantly, in many cases these early- to mid-transition metal catalysts have been shown to be as effective for heterocycle syntheses as the later (and more commonly implemented) group 9–11 metals.

In this Perspective, we discuss recent syntheses of 5- and 6-membered aromatic heterocycles via multicomponent reactions (MCRs) catalyzed by group 4–8 transition metals, with a focus on common mechanisms and synthetic strategies across the series.     

Catalyst-free arylation of sulfonamides via visible light-mediated deamination

A novel arylation of sulfonamides with boronic acids to afford numerous diaryl sulfones via a visible light-mediated N–S bond cleavage other than the typical transition-metal-catalyzed C(O)–N bond activation is described. This methodology, which represents the first catalyst-free protocol for the sulfonylation of boronic acids, is characterized by its simple reaction conditions, good functional group tolerance and high efficiency. Several successful examples for the late-stage functionalization of diverse sulfonamides indicate the high potential utility of this method in pharmaceutical science and organic synthesis.

The simple, catalyst-free sulfonylation of boronic acids with sulfonamides via a visible light-mediated N–S bond cleavage is described, affording diaryl sulfones with high efficiency. Late-stage functionalization of sulfonamide drugs was shown.     

Exploring benzylic gem-C(sp3)–boron–silicon and boron–tin centers as a synthetic platform

A stepwise build-up of multi-substituted C_sp³ carbon centers is an attractive, conceptually simple, but often synthetically challenging type of disconnection. To this end, this report describes how gem-α,α-dimetalloid-substituted benzylic reagents bearing boron/silicon or boron/tin substituent sets are an excellent stepping stone towards diverse substitution patterns. These gem-dimetalloids were readily accessed, either by known carbenoid insertion into C–B bonds or by the newly developed scalable deprotonation/metallation approach. Highly chemoselective transformations of either the C–Si (or C–Sn) or the C–B bonds in the newly formed gem-C_sp³ centers have been achieved through a set of approaches, with a particular focus on exploiting the synthetically versatile polarity reversal in organometalloids by λ³-aryliodanes. Of particular note is the metal-free arylation of the C–Si (or C–Sn) bonds in such gem-dimetalloids via the iodane-guided C–H coupling approach. DFT calculations show that this transfer of the (α-Bpin)benzyl group proceeds via unusual [5,5]-sigmatropic rearrangement and is driven by the high-energy iodine(iii) center. As a complementary tool, the gem-dimetalloid C–B bond is shown to undergo a potent and chemoselective Suzuki–Miyaura arylation with diverse Ar–Cl, thanks to the development of the reactive gem-α,α-silyl/BF₃K building blocks.

This work explores divergent reactivity of the benzylic gem-boron–silicon and boron–tin double nucleophiles, including the arylation of the C–B bond with Ar–Cl, along with a complementary oxidative λ³-iodane-guided arylation of the C–Si/Sn moiety.     

Site-selective amination and/or nitrilation via metal-free C(sp2)–C(sp3) cleavage of benzylic and allylic alcohols

Benzylic/allylic alcohols are converted via site-selective C(sp²)–C(sp³) cleavage to value-added nitrogenous motifs, viz., anilines and/or nitriles as well as N-heterocycles, utilizing commercial hydroxylamine-O-sulfonic acid (HOSA) and Et₃N in an operationally simple, one-pot process. Notably, cyclic benzylic/allylic alcohols undergo bis-functionalization with attendant increases in architectural complexity and step-economy.

Benzylic/allylic alcohols are converted via site-selective C(sp²)–C(sp³) cleavage to value-added nitrogenous motifs, viz., anilines and/or nitriles as well as N-heterocycles, utilizing commercial hydroxylamine-O-sulfonic acid (HOSA) and Et₃N in an operationally simple, one-pot process.