Overcoming the Oxygen Dilemma in Photoredox Catalysis: Near-Infrared (NIR) Light-Triggered Peroxynitrite Generation for Antibacterial Applications

The peroxynitrite anion (ONOO⁻) is closely associated with many diseases and the creation of ONOO⁻ donors is an essential means of understanding its pathophysiological functions. However, it is challenging to develop ONOO⁻ donors due to the difficulties in simultaneously producing highly reactive and short-lived nitric oxide (NO) and superoxide anion (O₂⋅⁻). Here, we report a novel strategy for constructing ONOO⁻ donors by combining near-infrared (NIR)-mediated type I photosensitization and photoredox catalysis. The key design using a Nile blue analogue that can serve as both a type I photosensitizer and a metal-free photocatalyst. Intriguingly, the formation of O₂⋅⁻ via type I photosensitization avoids oxygen interference and instead activates nitrobenzofurazan-based NO donors via oxygen-tolerant NIR photoredox catalysis. The simultaneous release of O₂⋅⁻ and NO leads to ONOO⁻ release, showing both antibacterial and antibiofilm activities.     

Density functional study on the role of electron donors in propylene polymerization using Ziegler-Natta catalyst

The role of electron donors in propylene polymerization using Ziegler-Natta model catalyst [TiCl₂CH₃]⁺ has been investigated using density functional calculations at B3LYP/6-31G* level. Methyl benzoate (MBz) and para-methoxy methyl benzoate (p-OMe-MBz) are the electron donors considered in this study. We have found two major roles of these electron donors that match well with the corresponding experimental results. First, for both the catalysts having different electron donors, the propylene insertion in Ti-CH₃ bond in syn-fashion rather than anti-fashion has lower activation barriers (E_act). This indicates that the regioselectivity of propylene insertion is maintained in the presence of the electron donors. Secondly, co-ordination of electron donors is found to increase the activation barriers of propylene insertion, which explains the experimentally observed drop in catalytic activity of [TiCl₂Me]⁺ on adding electron donors.     

A 13C n.m.r. study of the charge-transfer complexes between o-chloranil and some aromatic electron donors

The ¹³C n.m.r. spectra of complexes between o-chloranil and aromatic electron donors were studied. Complexation leads to a general diamagnetic shift of the ¹³C n.m.r. signals for the acceptor (o-chloranil), but for signals from the ¹³C nuclei in the donors both diamagnetic and paramagnetic shifts are found. These phenomena are thought to be the result of competing anisotropy and charge-migration effects. Charge migration in o-chloranil complexes appears to be more important than in corresponding 1,3,5-trinitrobenzene complexes.     

Highly Stereoselective β‐Mannopyranosylation via the 1‐α‐Glycosyloxy‐isochromenylium‐4‐gold(I) Intermediates

While the gold(I)‐catalyzed glycosylation reaction with 4,6‐O‐benzylidene tethered mannosyl ortho‐alkynylbenzoates as donors falls squarely into the category of the Crich‐type β‐selective mannosylation when Ph₃PAuOTf is used as the catalyst, in that the mannosyl α‐triflates are invoked, replacement of the ^?OTf in the gold(I) complex with less nucleophilic counter anions (i.e., ^?NTf₂, ^?SbF₆, ^?BF₄, and ^?BAr₄^F) leads to complete loss of β‐selectivity with the mannosyl ortho‐alkynylbenzoate β‐donors. Nevertheless, with the α‐donors, the mannosylation reactions under the catalysis of Ph₃PAuBAr₄^F (BAr₄^F=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate) are especially highly β‐selective and accommodate a broad scope of substrates; these include glycosylation with mannosyl donors installed with a bulky TBS group at O3, donors bearing 4,6‐di‐O‐benzoyl groups, and acceptors known as sterically unmatched or hindered. For the ortho‐alkynylbenzoate β‐donors, an anomerization and glycosylation sequence can also ensure the highly β‐selective mannosylation. The 1‐α‐mannosyloxy‐isochromenylium‐4‐gold(I) complex ( Cα ), readily generated upon activation of the α‐mannosyl ortho‐alkynylbenzoate ( 1 α ) with Ph₃PAuBAr₄^F at ?35 °C, was well characterized by NMR spectroscopy; the occurrence of this species accounts for the high β‐selectivity in the present mannosylation.     

Structural characterization,thermal stability,and solvent de-/ad-sorption behavior of two d10 M(II) (M = Cd and Zn) coordination polymers constructed by 1,3,5-tris(4-pyridylsulfanyl-methyl)-2,4,6-trimethyl-benzene (L1)

Two d¹⁰ M(II) (M = Cd and Zn) coordination polymers (CPs) with chemical formulas, {[Cd(L¹)(NCS)₂(H₂O)]⋅C₂H₅OH}_n (1) , and {[Zn(L¹)(NCS)₂]⋅C₂H₅OH⋅0.5H₂O}_n (2) (L¹ = 1,3,5-tris(4-pyridylsulfanylmethyl)-2,4,6-trimethylbenzene) were synthesized and structurally characterized by single-crystal x-ray diffraction method. In compound 1 , the coordination environment of Cd(II) ion is distorted octahedral bonded to three nitrogen donors from three L¹ ligands located in a facial-position, two nitrogen donors from NCS⁻ and one water molecule. The L¹ acts as a bridge ligand with tris-monodentate coordination mode in a cis-cis-cis structural conformation, connecting the Cd(II) to form a two-dimensional (2D) zigzag-like layered metal-organic frameworks. Adjacent 2D layers are then arranged orderly in an ABAB manner to complete its three-dimensional (3D) supramolecular architecture. In compound 2 , the coordination environment of Zn(II) ion is distorted tetrahedral bonded to two nitrogen donors from two L¹ ligands and two nitrogen donors from two NCS⁻ ligands. The L¹ acts as a bridge ligand with bis-monodentate coordination mode in a cis-cis-cis structural conformation, connecting the Zn(II) ions to form a one-dimensional (1D) zigzag-like polymeric chain. Adjacent chains are arranged orderly in an alternate ABAB manner to generate a 2D framework and then further arranged in an AAA manner to complete its 3D supramolecular architecture. The structural characterization as well as thermal-stability and solvents de-/ad-sorption behavior of 1 and 2 are studied and discussed in details.     

(1,3‐Dimethylimidazolidine‐2‐selone‐κSe)bis(1,10‐phenanthroline‐κ2N,N′)copper(II) bis(perchlorate) and bis(2,2′‐bipyridyl‐κ2N,N′)(imidazolidine‐2‐thione‐κS)copper(II) bis(perchlorate)

In the first title salt, [Cu(C₁₂H₈N₂)₂(C₅H₁₀N₂Se)](ClO₄)₂, the Cu^II centre occupies a distorted trigonal–bipyramidal environment defined by four N donors from two 1,10‐phenanthroline (phen) ligands and by the Se donor of a 1,3‐dimethylimidazolidine‐2‐selone ligand, with the equatorial plane defined by the Se and by two N donors from different phen ligands and the axial sites occupied by the two remaining N donors, one from each phen ligand. The Cu—N distances span the range 1.980 (10)–2.114 (11) Å and the Cu—Se distance is 2.491 (3) Å. Intermolecular π–π contacts between imidazolidine rings and the central rings of phen ligands generate chains of cations. In the second salt, [Cu(C₁₀H₈N₂)₂(C₃H₆N₂S)](ClO₄)₂, the Cu^II centre occupies a similar distorted trigonal–bipyramidal environment comprising four N donors from two 2,2′‐bipyridyl (bipy) ligands and an S donor from an imidazolidine‐2‐thione ligand. The equatorial plane is defined by the S donor and two N donors from different bipy ligands. The Cu—N distances span the range 1.984 (6)–2.069 (7) Å and the Cu—S distance is 2.366 (3) Å. Intermolecular π–π contacts between imidazolidine and pyridyl rings form chains of cations. A major difference between the two structures is due to the presence in the second complex of two N—H...O hydrogen bonds linking the imidazolidine N—H hydrogen‐bond donors to perchlorate O‐atom acceptors.     

Stereoselectivity of glycosylations of conformationally restricted mannuronate esters

Glycosidation of conformationally unrestricted mannuronate ester donors proceeds in a highly β-selective fashion, whereas condensations of mannuronate ester donors, which are conformationally constrained by a 3,4-butanedimethylacetal or a 2,3-isopropylidene function, provide α-selective products. We hypothesize that the difference in stereochemical outcome of these condensations results from the different conformations of the product forming oxacarbenium intermediate. The formation of the β-linked products from the flexible mannuronates is thought to originate from the most favorable ³H₄ oxacarbenium ion, which is not accessible from the conformationally restrained donors. Although an α-triflate intermediate is formed upon activation of the 3,4-butanedimethylacetal protected mannuronate ester thio donor, this is not the product forming intermediate. The anomeric triflate serves as a reservoir for the ⁴H₃ oxacarbenium ion, which is glycosidated to provide the α-linked mannuronates.     

Crystallographic Evidence for a Sterically Induced Ferryl Tilt in a Non‐Heme Oxoiron(IV) Complex that Makes it a Better Oxidant

Oxoiron(IV) units are often implicated as intermediates in the catalytic cycles of non‐heme iron oxygenases and oxidases. The most reactive synthetic analogues of these intermediates are supported by tetradentate tripodal ligands with N‐methylbenzimidazole or quinoline donors, but their instability precludes structural characterization. Herein we report crystal structures of two [Fe^IV(O)(L)]²⁺ complexes supported by pentadentate ligands incorporating these heterocycles, which show longer average Fe–N distances than the complex with only pyridine donors. These longer distances correlate linearly with log k₂′ values for O‐ and H‐atom transfer rates, suggesting that weakening the ligand field increases the electrophilicity of the Fe=O center. The sterically bulkier quinoline donors are also found to tilt the Fe=O unit away from a linear N‐Fe=O arrangement by 10°.     

Cathodic Hydrogen Evolution from Aqueous Solutions of Acetic Acid

In continuation of the work on establishing hydrogen donors in the hydrogen evolution reaction from different acid molecules, cathodic evolution of hydrogen on silver is investigated from solutions of monobasic acetic acid with the aim to establish the origin of reduced hydrogen. Solutions of 0.2 M acetic acid with 0.2 M perchloric acid, neutralized to different pH values by NaOH, are used. The earlier established criterion is used for discerning between two possible hydrogen evolution mechanisms: (1) from dissociated hydrogen ions and (2) from undissociated hydrogen atoms in the molecule. At medium pH values, the undissociated acid molecules participate as hydrogen donors. Rate constants for reactions 1 and 2, evaluated at a potential of –800 mV (SCE), at which the entire pH range can be scanned, are 2.9 × 10^–6 and 1.9 × 10^–8.     

Synthesis and phase-transfer catalytic activity of crown ethers bound to microporous polystyrene resins by oxyethylene spacers

Crown ethers bound to microporous polystyrene resins by oxyethylene spacers were prepared by the reaction of monoazacrown ethers with 2-tosyloxyethoxymethylated or 2-(2-tosyloxyethoxy)ethoxymethylated polystyrene resins crosslinked with 2 mol % of divinylbenzene. The activity of the immobilized lariat crowns for halogen exchange reactions under triphase conditions has been studied as a function of catalyst structure, loading, substrate structure, reagent structure, and solvent. The lariat catalysts with extra oxygen donors in the spacer chain exhibited higher activity than the corresponding immobilized catalysts without the donors in the spacer. The increased activity of the catalyst containing 15-crown-5 unit and two extra donors for the reaction of 1-bromooctane with KI was concluded to result from the enhanced complexation with the K⁺ ion, induced by the cooperative coordination of the crown unit donors and the donors in the spacer chain. The recovered catalysts could be re-used without decrease in activity.     

Photoactive Ruthenium Nitrosyls: Effects of Light and Potential Application as NO Donors

In recent years, various exogenous nitric oxide (NO) donors have been synthesized to modulate NO concentrations in cellular environments and control physiological processes that are regulated by NO. Transition metal complexes of NO (metal nitrosyls) are one such class of NO donors. Since complexes of ruthenium are in general more stable, a variety of ruthenium nitrosyls have been isolated and studied in detail in terms of their NO donating capacities. A large number of {Ru–NO}⁶ type of nitrosyls release NO upon exposure to UV light. Several research groups have studied their photochemistry to evaluate their potential as NO donors under the control of light. In general, the nitrosyls with non-porphyrin ligands (such as amines, Schiff bases, thiolates and ligands with carboxamide groups) readily release NO upon illumination and generate Ru(III) photoproducts. In contrast, NO photorelease from ruthenium nitrosyls derived from porphyrins remains limited due to rapid recombination. In some cases, the {Ru–NO}⁶ nitrosyls are photochemically converted to nitrite species (especially in water at neutral pH) while a few afford Ru(II) photoproducts. UV irradiation of selected ruthenium nitrosyls in the solid state results in NO linkage isomerism. To date, notable progress has been made in the area of nitrosyl-polymer hybrids that could be used for site-specific delivery of NO. Various strategies have also been developed to make these nitrosyls release NO under the influence of visible and/or near IR light. Although some ruthenium nitrosyls are stable under physiological conditions and are capable to NO delivery to proteins such as myoglobin and cytochrome c oxidase, so far success has been limited in using these nitrosyls as light-activated NO donors in cellular and tissue models. In this review, the effects of light on ruthenium nitrosyls derived from a wide variety of ligands (reported so far) have been summarized and their utility as NO donors have been discussed.     

Thermochemical and spectrophotometrical study of Ni(II) Complexes with Thiadiamines

Ni(II) complexes of some linear tridentates with one sulphur and two nitrogen donors have been studied in aqueous solution at 25°C in 0.5 M (K)NO₃ medium by means of the calorimetric and spectrophotometric technique. It is shown that the percentage facial isomer in the NiL²⁺ complexes becomes more important with increasing substitution on the nitrogen or sulphur donor atoms. The NiL₂²⁺ complexes most probably have a trans-facial tetragonally distorted structure with four equatorially bound nitrogen donors and in axial position the sulphide donors. The same {Ni-(N₄S₂)}²⁺ cation was also present in the NiL₂(NO₃)₂ solid state compounds.     

Rate constants for hydrogen abstraction by resonance stabilized radicals in high temperature liquids

Benzylic H-atom abstraction rates by diphenylmethyl radicals from a series of donors were determined in nonpolar liquids at elevated temperatures. Relative rates were converted to absolute rates via available equilibrium constant data for the dimerization of diphenylmethyl radicals. Abstraction by diphenylmethyl from 1, 2, 3, 4-tetrahydronaphthalene (tetralin) was studied over the temperature range 489–573 K. Its Arrhenius expression is 10^9.9±0.3 exp{?(10183 ± 373)/T} M^?1 s^?1. Abstraction from other donors was studied at 548 K. Rate constant values ranged from a low of 3.6 M^?1 s^?1 for toluene to a high of 3000 M^?1 s^?1 for 9, 10-dihydroanthracene. Similar reactions with the fluorenyl radical were also studied. In this case, relative rates were converted to absolute rates with an equilibrium constant for fluorenyl dimerization determined from the observed homolysis rate of the dimer and an assumed recombination rate. In addition, forward and reverse rate measurements yielded the equilibrium constant for hydrogen transfer between fluorenyl and diphenylmethyl. At 548 K, fluorenyl is favored by a factor of 13 over diphenylmethyl.     

O→S Relay Deprotection: A General Approach to Controllable Donors of Reactive Sulfur Species

Reactive sulfur species (RSS) are biologically important molecules. Among them, H₂S, hydrogen polysulfides (H₂S_n, n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur‐related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O‐silyl‐mercaptan‐based sulfur‐containing molecules which undergo pH‐ or F^?‐mediated desilylation to release the corresponding H₂S, H₂S_n, RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH‐ or F^?‐triggered RSS donors. Moreover, we have demonstrated that the O‐silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase‐activated donors).     

Diverse Coordination Geometries Derived from Trisaminocyclohexane Ligands with Appended Outer-Sphere Hydrogen Bond Donors

With the aim of constructing hydrogen-bonding networks in synthetic complexes, two new ligands derived from cis,cis-1,3,5-triaminocyclohexane (TACH) have been prepared that feature pendant pyrrole or indole rings as outer-sphere H-bond donors. The TACH framework offers a facial arrangement of three N-donors, thereby mimicking common coordination motifs in the active sites of nonheme Fe and Cu enzymes. X-ray structural characterization of a series of Cu^I-X complexes (X=F, Cl, Br, NCS) revealed that these neutral ligands (H₃L^R, R=pyrrole or indole) coordinate in the intended facial N₃ manner, yielding four-coordinate complexes with idealized C₃ symmetry. The N−H units of the outer-sphere heterocycles form a hydrogen-bonding cavity around the axial (pseudo)halide ligand, as verified by crystallographic, spectroscopic, and computational analyses. Treatment of H₃L^pyrrole and H₃L^indole with divalent transition metal chlorides (M^IICl₂, M=Fe, Cu, Zn) causes one heterocycle to deprotonate and coordinate to the M(II) center, giving rise to tetradentate ligands with two remaining outer-sphere H-bond donors. Further ligand deprotonation is observed upon reaction with Ni(II) and Cu(II) salts with weakly coordinating counteranions. The reported complexes highlight the versatility of TACH-based ligands with pendant H-bond donors, as the resulting scaffolds can support multiple protonation states, coordination geometries, and H-bonding interactions.     

HNO trapping and assisted decomposition of nitroxyl donors by ferric hemes

The role of nitric oxide (NO) as a signalling molecule in biological systems has been thoroughly studied in the last decades. More recently, there has been an increasing interest in the one-electron reduction product of NO, namely nitroxyl (HNO/NO⁻). Some studies suggest that nitroxyl can be produced by nitric oxide synthases under certain conditions, and that distinct pharmacological effects are observed for NO and nitroxyl donors. HNO is capable of react with heme proteins, thiols, molecular oxygen, NO and HNO itself. However, only recently the different reactivity patterns are being thoroughly understood. Heme model compounds offer the opportunity to study the reaction kinetics without the complexity arising from ligand interactions with the protein matrix. In this study we analyzed the reaction between the commonly used nitroxyl donors sodium trioxodinitrate and toluene sulfohydroxamic acid, with the ferric model compounds microperoxidase-11 (MP11) and the cationic metalloporphyrin [Fe^IIITEPyP]⁵⁺ (Tetrakis N-ethylpyridinium-2yl porphyne). Our results show that there are two alternative modes of reactivity for nitroxyl donors towards heme in aqueous solutions. The first one comprises the heme assisted decomposition of the donor, enhancing its decomposition rate more than 100-fold. In the second, the donor produces HNO which subsequently reacts with the porphyrin. The observed rate constants (of about 10⁵ M⁻¹ s⁻¹) are consistent with the estimated data for the HNO reaction with heme proteins, and may be controlled by the leaving water ligand. This rate constant probably represents an upper limit for the bimolecular rate constant of HNO towards these proteins.     

O-(1-Phenyl-1H-tetrazol-5-yl) Glycosides: Alternative synthesis and transformation into glycosyl fluorides

A number of new glycosyl donors, O-(1-phenyl-1H-tetrazol-5-yl) glycosides, are prepared from the corresponding hemiacetals, commercially available 5-chloro-1-phenyl-1H-tetrazole ( 2 ), and tetrabutylammonium fluoride (Bu₄NF) in either THF or DMF. The mild reaction conditions are compatible with a variety of protecting groups. The glycosyl donors are treated with hydrogen fluoride-pyridine complex (HF·py) to rapidly provide glycosyl fluorides in good-to-excellent yields, apparently by a (single or double) S_N2 mechanism as studied by both ¹H- and ¹⁹F-NMR spectroscopy. Under acidic conditions, glycosyl fluorides equilibrate partially or completely, equilibration requiring a large excess of HF · py.     

DFT and IsoStar Analyses to Assess the Utility of σ- and π-Hole Interactions for Crystal Engineering

The interpretation of 36 charge neutral ‘contact pairs’ from the IsoStar database was supported by DFT calculations of model molecules 1 – 12 , and bimolecular adducts thereof. The ‘central groups’ are σ-hole donors (H₂O and aromatic C−I), π-hole donors (R−C(O)Me, R−NO₂ and R−C₆F₅) and for comparison R−C₆H₅ (R=any group or atom). The ‘contact groups’ are hydrogen bond donors X−H (X=N, O, S, or R₂C, or R₃C) and lone-pair containing fragments (R₃C−F, R−C≡N and R₂C=O). Nearly all the IsoStar distributions follow expectations based on the electrostatic potential of the ‘central-’ and ‘contact group’. Interaction energies (ΔE^BSSE) are dominated by electrostatics (particularly between two polarized molecules) or dispersion (especially in case of large contact area). Orbital interactions never dominate, but could be significant (∼30 %) and of the n/π→σ*/π* kind. The largest degree of directionality in the IsoStar plots was typically observed for adducts more stable than ΔE^BSSE≈−4 kcal⋅mol⁻¹, which can be seen as a benchmark-value for the utility of an interaction in crystal engineering. This benchmark could be met with all the σ- and π-hole donors studied.     

Physical and Chemical Interaction of Homoconjugated Dienes with Tetracyanoethylene

EDA-complexes of bicyclo[2,2,n]alkadienes (n = 1, 2, 3, 4) ( 1 (n)-series), 1,4-cyclohexadiene ( 2 ) and various other cyclic monoenes, dienes and trienes as donors and tetracyanoethylene (TCNE) as acceptor were investigated. Spectroscopic and thermodynamic constants of the complexes were determined and correlated with the ionisation potentials (I^D) of the hydrocarbon donors obtained from PE. spectroscopy. The nature of the dominant energy contributions to the ground state and the two lowest CT-states of these weak complexes is discussed and structural conclusions are drawn. The role of the complexes in the addition reaction of the hydrocarbon components and TCNE is discussed. The homo Diels-Alder addition product of 1 (2) and TCNE, 9,9,10,10-tetracyanoquadricyclo[2,2,2,0^2,6,2^3,5]decane, and the ‘ene’-addition product of 2 and TCNE, 5-[1′,1′,2′,2′-tetracyanoethyl]-1,3-cyclohexadiene were prepared and characterized. Preliminary results for the mechanistic scheme governing the dehydrogenation of 2 by TCNE are reported.     

Effect of the 67Zn isotope on leukemic cells and normal lymphocytes

Porphyrinofullerene nanoparticles (NP) containing magnetic isotopes ²⁵Mg and ⁶⁷Zn (²⁵Mg-NP and ⁶⁷Zn-NP) and the natural isotopic composition of zinc (Zn) were tested on human leukemic cells of patients with acute leukemia and on lymphocytes of healthy donors. The fundamental differences in the cytotoxic effect of magnetic and nonmagnetic zinc isotopes on tumor cells were observed, as well as the complete absence of the influence of the magnetic magnesium isotope and pristine nanoparticles. The ⁶⁷Zn-NP manifested high cytotoxicity towards cells of acute B-lymphoblast leukemia with LD₅₀ almost three times lower than that of healthy donors and four times lower than that of the Zn-NP. Apoptosis was evaluated by cytofluorimetry for the drugs used.