Alkyl Chain Appended Fe(III) Catecholate Complex as a Dual-Modal T1 MRI-NIR Fluorescence Imaging Agent via Second Sphere Water Interactions.

The C12-alkyl chain-conjugated Fe(III) catecholate complex [Fe(C12CAT)3]3-, Fe(C12CAT)3 [C12CAT = N-(3,4-dihydroxyphenethyl)dodecanamide], was synthesized and characterized, reported as a dual-modal T1-MRI and an optical imaging probe. The DFT-optimized structure of Fe(C12CAT)3 reveals a distorted octahedral coordination geometry around the high spin Fe(III) center. The formation constant (-log K) of Fe(C12CAT)3 was calculated as 45.4. The complex exhibited r1-relaxivity values of 2.31 ± 0.12 and 1.52 ± 0.06 mM-1 s-1 at 25 and 37 °C, respectively, on 1.41 T at pH 7.3 via second-sphere water interactions. The interaction of Fe(C12CAT)3 with human serum albumin showed concomitant enhancement of r1-relaxivity to 6.44 ± 0.15 mM-1 s-1. The MR phantom images are significantly brighter and directly correlate to the concentration of Fe(C12CAT)3. Adding an external fluorescent marker IR780 dye to Fe(C12CAT)3 leads to the formation of self-assembly by C12-alkyl chains. It resulted in the fluorescence quenching of the dye, and its critical aggregation concentration was calculated as 70 µM. The aggregated matrix of Fe(C12CAT)3 and IR780 dye is spherical, with an average hydrodynamic diameter of 189.5 nm. This self-assembled supramolecular system is found to be non-fluorescent and was "turn-on" under acidic pH via dissociation of aggregates. The r1-relaxivity is found to be unchanged during the matrix aggregation and disaggregation. The probe showed MRI ON and fluorescent OFF under physiological conditions and MRI ON and fluorescent ON under acidic pH. The cell viability experiments showed that the cells are 80% viable at 1 mM probe concentration. Fluorescence experiments and MR phantom images showed that Fe(C12CAT)3 is a potential dual model imaging probe to visualize the acidic pH environment of the cells.

Nickel(II) Complexes of Tripodal Ligands as Catalysts for Fixation of Atmospheric CO2 as Organic Carbonates.

The fixation of atmospheric CO2 into value-added products is a promising methodology. A series of novel nickel(II) complexes of the type [Ni(L)(CH3 CN)2 ](BPh4 )2 1-5, where L=N,N-bis(2-pyridylmethyl)-N', N'-dimethylpropane-1,3-diamine (L1), N,N-dimethyl-N'-(2-(pyridin-2-yl)ethyl)-N'-(pyridin-2-ylmethyl) propane-1,3-diamine (L2), N,N-bis((4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-N',N'-dimethylpropane-1,3-diamine (L3), N-(2-(dimethylamino) benzyl)-N',N'-dimethyl-N-(pyridin-2-ylmethyl) propane-1,3-diamine (L4) and N,N-bis(2-(dimethylamino)benzyl)-N', N'-dimethylpropane-1,3-diamine (L5) have been synthesized and characterized as the catalysts for the conversion of atmospheric CO2 into organic cyclic carbonates. The single-crystal X-ray structure of 2 was determined and exhibited distorted octahedral coordination geometry with cis-α configuration. The complexes have been used as a catalyst for converting CO2 and epoxides into five-membered cyclic carbonates under 1 atmospheric (atm) pressure at room temperature in the presence of Bu4 NBr. The catalyst containing electron-releasing -Me and -OMe groups afforded the maximum yield of cyclic carbonates, 34% (TON, 680) under 1 atm air. It was drastically enhanced to 89% (TON, 1780) under pure CO2 gas at 1 atm. It is the highest catalytic efficiency known for CO2 fixation using nickel-based catalysts at room temperature and 1 atm pressure. The electronic and steric factors of the ligands strongly influence the catalytic efficiency. Furthermore, all the catalysts can convert a wide range of epoxides (ten examples) into corresponding cyclic carbonate with excellent selectivity (>99%) under this mild condition.

DFT insights into the mechanism of O2 activation catalyzed by a structural and functional model of cysteine dioxygenase with tris(2-pyridyl)methane-based ligand architecture.

Cysteine dioxygenation is an important step in the metabolism of toxic L-cysteine (Cys) in the human body, carried out by cysteine dioxygenase enzyme (CDO). The disruption of this process is found to elicit neurological health issues. This work reports a computational investigation of mechanistic aspects of this reaction, using a recently reported tris(2-pyridyl)methane-based biomimetic model complex of CDO. The computed results indicate that, the initial SO2 bond formation process is the slowest step in the S-dioxygenation process, possessing an activation barrier of 12.7 kcal/mol. The remaining steps were found to be downhill requiring very small activation energies. The transition states were found to undergo spin crossover between triplet and quintet states, while the singlet surface remained unstable throughout the entire reaction. In essence, the mechanistic scheme and multistate reactivity pattern together with the relatively small computed rate-limiting activation barrier as well as the exothermic formation energy demonstrate that the model complex is an efficient biomimetic CDO model. In addition, the study also substantiates the involvement of Fe(IV)oxido intermediates in the mechanism of S-dioxygenation by the chosen model complex. The insights derived from the O2 activation process might pave way for development of more accurate CDO model catalysts that might be capable of even more efficiently mimicking the geometric, spectroscopic and functional features of the CDO enzyme.

Mn(II) complexes of phenylenediamine based macrocyclic ligands as T1-MRI contrast agents.

The Mn(II) complexes are emerging as alternative T1-MRI contrast agents (CAs) to the currently available Gd-based CAs. The complexes [Mn(L1)] 1 and [Mn(L2)] 2 of o-phenylenediamine based macrocyclic ligands are reported as T1-CAs for MRI applications. The high spin state of the Mn(II) complexes (S = 5/2) is confirmed by EPR spectra. The complexes showed an irreversible Mn(II)/Mn(III) redox potential at pH 7.28, which became more and less positive at the acidic and alkaline pHs, respectively. The species [MnL], [Mn(LH-1), and [Mn(LH-2) are persisted in solution. Complex 1 is inert towards Ca(II), Mg(II), and Zn(II), whereas complex 2 is inert for Ca(II) and Mg(II) and labile under Zn(II) and Cu(II) ions. Complex 1 showed an r1-relaxivity of 3.27 and 2.32 mM-1 s-1 at 1.41 T, 25, and 37 °C respectively via inner-sphere water relaxation, which is lower than that of 2 (r1, 5.56, and 4.19 mM-1 s-1) at pH 7.28 and 1.41 T. The Mn(II) complexes showed a 2-8% enhancement of r1-relaxivity while lowering the pH to acidic, which corresponds to the release of free Mn(II) ions. In contrast, the r1-relaxivity is dropped to 52% and 20% for 1 and 2 respectively under alkaline pH due to the deprotonation of inner-sphere water. Phantom images obtained on Bruker 'BIOSPEC' 47/40 animal research MRI/MRS scanner showed concentration-dependent brightness. The interaction of human serum albumin (HSA) with 1 and 2 exhibited five times higher r1-relaxivities (11.3 and 22.0 mM-1 s-1 at 1.41 T, respectively).

Fixation of atmospheric CO2 as C1-feedstock by nickel(ii) complexes.

The development of molecular catalysts for the activation and conversion of atmospheric carbon dioxide (CO2) into a value-added product is a great challenge. A series of nickel(ii) complexes, [Ni(L)(CH3CN)3](BPh4)2, 1-4 of diazepane based ligands, 4-methyl-1-[(pyridin-2-yl-methyl)]-1,4-diazepane (L1), 4-methyl-1-[2-(pyridine-2-yl)ethyl]-1,4-diazepane (L2), 4-methyl-1-[(quinoline-2-yl)-methyl]-1,4-diazepane (L3) and 1-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl]-4-methyl-1,4-diazepane (L4), have been synthesized and characterized as catalysts for the activation of atmospheric CO2. The single-crystal X-ray structure of 1 shows a distorted octahedral geometry with a cis-ß configuration around the NiN6 coordination sphere. All the complexes are used as catalysts for the conversion of atmospheric CO2 and epoxides into cyclic carbonates at 1 atmosphere (atm) pressure and in the presence of Et3N. Catalyst 4 was found to be the most efficient catalyst and showed a 31% formation of cyclic carbonates with a TON of 620 under 1 atm air as the CO2 source. This yield was enhanced to 94% with a TON of 1880 under 1 atm pure CO2 gas and it is the highest catalytic efficiency known for nickel(ii)-based catalysts. Catalyst 4 enabled the transformation of a wide range of epoxides (eight examples) into corresponding cyclic carbonates with excellent selectivity (>99%) and yields of 59-94% and 11-31% under pure CO2 and atmospheric CO2, respectively. The catalytic efficiency is strongly influenced by the electronic nature of the complexes. The CO2 fixation reactions without an epoxide substrate led to the formation of the carbonate bridged dinuclear nickel(ii) complexes [(LNiII)2CO3](BPh4)21a-4a, which are speculated as catalytically active intermediates. The formation of these species was accompanied by the formation of new absorption bands around 592-681 nm and was further confirmed by the ESI-MS and IR spectral studies. The molecular structures of these carbonate-bridged key intermediates were determined by X-ray analysis. The structures contain two Ni2+-centers bridged via a carbonate ion that originated from CO2. Distorted square pyramidal geometries are adopted around each Ni(ii) center. All these results support that CO2 fixation reactions occur via CO2-bound nickel key intermediates.

Copper(II) complexes of tripodal ligand scaffold (N3O) as functional models for phenoxazinone synthase.

The copper(II) complexes [Cu(L)NO3] (1-9) of newer N3O ligands (L1-L9) have been synthesized and characterized. The molecular structure of 1, 4, and 7 exhibited nearly a perfect square pyramidal geometry (τ, 0.04-0.11). The Cu-OPhenolate bonds (~ 1.91 Å) are shorter than the Cu-N bonds (~ 2.06 Å) due to the stronger coordination of anionic phenolate oxygen. The Cu(II)/Cu(I) redox potentials of 1-9 appeared around -0.102 to -0.428 V versus Ag/Ag+ in water. The electronic spectra of the complexes showed the d-d transitions around 643-735 nm and axial EPR parameter (g||, 2.243-2.270; A||, 164-179 × 10-4 cm-1) that corresponds to square pyramidal geometry. The bonding parameters α2, 0.760-0.825; ß2, 0.761-0.994; γ2, 0.504-0.856 and K||, 0.698-0.954 and K⊥, 0.383-0.820 calculated from EPR spectra and energies of d-d transitions. The complexes catalyzed the conversion of substrate 2-aminophenol into 2-aminophenoxazine-3-one using molecular oxygen in the water and exhibited the yields of 41-61%. The formation of the product is accomplished by the appearance of a new absorption band at 430 nm and the rates of formation were calculated as 6.98-15.65 × 10-3 s-1 in water. The reaction follows Michaelis-Menten enzymatic reaction kinetics with turnover numbers (kcat) 9.11 × 105 h-1 for 1 and 4.66 × 105 h-1 for 9 in water. The spectral, redox and kinetic studies were performed in water to mimic the enzymatic oxidation reaction conditions.

Cu(I) complexes obtained via spontaneous reduction of Cu(II) complexes supported by designed bidentate ligands: bioinspired Cu(I) based catalysts for aromatic hydroxylation.

Copper(i) complexes [Cu(L1-7)2](ClO4) (1-7) of bidentate ligands (L1-L7) have been synthesized via spontaneous reduction and characterized as catalysts for aromatic C-H activation using H2O2 as the oxidant. The single crystal X-ray structure of 1 exhibited a distorted tetrahedral geometry. All the copper(i) complexes catalyzed direct hydroxylation of benzene to form phenol with good selectivity up to 98%. The determined kinetic isotope effect (KIE) values, 1.69-1.71, support the involvement of a radical type mechanism. The isotope-labeling experiments using H218O2 showed 92% incorporation of 18O into phenol and confirm that H2O2 is the key oxygen supplier. Overall, the catalytic efficiencies of the complexes are strongly influenced by the electronic and steric factor of the ligand, which is fine-tuned by the ligand architecture. The benzene hydroxylation reaction possibly proceeded via a radical mechanism, which was confirmed by the addition of radical scavengers (TEMPO) to the catalytic reaction that showed a reduction in phenol formation.

Smart dual T1 MRI-optical imaging agent based on a rhodamine appended Fe(III)-catecholate complex.

A rhodamine appended Fe(iii)-catecholate complex Fe(RhoCat)3 is reported as a smart dual-modal T1 MRI-optical imaging probe. The high spin Fe(iii) coordination sphere and rhodamine unit act as MRI and optical reporters, respectively. The probe showed a r1-relaxivity of 4.37 mM-1 s-1 at 1.41 T via the interaction of second sphere water molecules to coordinated oxygen atoms. It produced an enhanced signal intensity of phantom images on the 7.0 T animal research MRI/MRS scanner at 25 °C and pH 7.3. The interaction of the probe with bovine serum albumin (BSA) significantly improved r1 relaxivity (7.09 mM-1 s-1). Moreover, the optical imaging reporter rhodamine moiety exhibited sensitivity towards biomolecule nitric oxide (NO) and acidic pH via the formation of a ring-opened tautomer of rhodamine, wherein the r1 relaxivity of the probe was enhanced to 5.19 mM-1 s-1 for NO and slightly decreased for acidic pH. Further, the probe visualized NO in adenocarcinoma gastric (AGS) cells via a turn-on fluorescence mechanism with 80% cell viability. Thus, Fe(RhoCat)3 is demonstrated as a potential dual "MRI-ON and Fluorescence-ON" molecular imaging probe to visualize the NO molecule and acidic pH in the tumour microenvironment.

Benzene Hydroxylation by Bioinspired Copper(II) Complexes: Coordination Geometry versus Reactivity.

A series of bioinspired copper(II) complexes of N4-tripodal and sterically crowded diazepane-based ligands have been investigated as catalysts for functionalization of the aromatic C-H bond. The tripodal-ligand-based complexes exhibited distorted trigonal-bipyramidal (TBP) geometry (τ, 0.70) around the copper(II) center; however, diazepane-ligand-based complexes adopted square-pyramidal (SP) geometry (τ, 0.037). The Cu-NPy bonds (2.003-2.096 Å) are almost identical and shorter than Cu-Namine bonds (2.01-2.148 Å). Also, their Cu-O (Cu-Owater, 1.988 Å; Cu-Otriflate, 2.33 Å) bond distances are slightly varied. All of the complexes exhibited Cu2+ → Cu+ redox couples in acetonitrile, where the redox potentials of TBP-based complexes (-0.251 to -0.383 V) are higher than those of SP-based complexes (-0.450 to -0.527 V). The d-d bands around 582-757 nm and axial patterns of electron paramagnetic resonance spectra [g∥, 2.200-2.251; A∥, (146-166) × 10-4 cm-1] of the complexes suggest the existence of five-coordination geometry. The bonding parameters showed K∥ > K⊥ for all complexes, corresponding to out-of-plane π bonding. The complexes catalyzed direct hydroxylation of benzene using 30% H2O2 and afforded phenol exclusively. The complexes with TBP geometry exhibited the highest amount of phenol formation (37%) with selectivity (98%) superior to that of diazepane-based complexes (29%), which preferred to adopt SP-based geometry. Hydroxylation of benzene likely proceeded via a CuII-OOH key intermediate, and its formation has been established by electrospray ionization mass spectrometry, vibrational, and electronic spectra. Their formation constants have been calculated as (2.54-11.85) × 10-2 s-1 from the appearance of an O (π*σ) → Cu ligand-to-metal charge-transfer transition around 370-390 nm. The kinetic isotope effect (KIE) experiments showed values of 0.97-1.12 for all complexes, which further supports the crucial role of Cu-OOH in catalysis. The 18O-labeling studies using H218O2 showed a 92% incorporation of 18O into phenol, which confirms H2O2 as the key oxygen supplier. Overall, the coordination geometry of the complexes strongly influenced the catalytic efficiencies. The geometry of one of the CuII-OOH intermediates has been optimized by the density functional theory method, and its calculated electronic and vibrational spectra are almost similar to the experimentally observed values.

Catalytic Conversion of Atmospheric CO2 into Organic Carbonates by Nickel(II) Complexes of Diazepane-Based N4 Ligands.

Activation of CO2 and conversion into value-added products is an effective option to mitigate CO2 emission. The nickel(II) complexes [Ni(L1)](ClO4)2 1, [Ni(L2)](ClO4)2 2, and [Ni(L3)(CH3CN)2](Ph4B)2 3 of diazepane-based ligands [1,4-bis[(pyridin-2-yl-methyl)]-1,4-diazepane (L1), 1,4-bis[2-(pyridin-2-yl)ethyl]-1,4-diazepane (L2), and 4-bis[2-(quinoline-2-yl)-methyl]-1,4-diazepane (L3)] have been synthesized and structurally characterized. The complexes were employed as the catalysts for the conversion of atmospheric CO2 into organic carbonates in the absence of cocatalyst at 1 atm pressure. The single-crystal X-ray structures of 1 and 2 exhibit distorted square-planar geometry with almost identical Ni-N bond distances (1.891-1.946 Å). The geometry of the complexes rearranged into octahedral in acetonitrile, which was studied by paramagnetic 1H NMR and electronic spectra. The complexes selectively captured CO2 from the atmospheric air and readily converted epoxides into cyclic carbonates without any cocatalyst. They showed a maximum yield of 25% (TON, 500) using 1 atm air, which is drastically enhanced up to 89% (TON, 1780) using 1 atm pure CO2 gas. This is the highest catalytic efficiency reported for CO2 fixation using nickel-based catalysts to date. The CO2 fixation reaction without organic substrate showed the formation of carbonate-bridged dinuclear nickel(II) complexes. They showed characteristic absorption bands around 571-612 nm and were further confirmed by electrospray ionization mass spectrometry, IR, and single-crystal X-ray structures. The molecular structure of carbonate-bridged intermediates exhibited two Ni2+-centers with distorted square pyramidal geometries for 2a and 3a but distorted octahedral and square pyramidal geometries for 1a. The CO2 fixation reactions possibly proceeded via the formation of CO2-bound nickel species.

Bioinspired models for an unusual 3-histidine motif of diketone dioxygenase enzyme.

Bioinspired models for contrasting the electronic nature of neutral tris-histidine with the anionic 2-histidine-1-carboxylate facial motif and their subsequent impact on catalysis are reported. Herewith, iron(ii) complexes [Fe(L)(CH3CN)3](SO3CF3)21-3 of tris(2-pyridyl)-based ligands (L) have been synthesized and characterized as accurate structural models for the neutral 3-histidine triad of the enzyme diketone dioxygenase (DKDO). The molecular structure of one of the complexes exhibits octahedral coordination geometry and Fe-N11py bond lengths [1.952(4) to 1.959(4) Å] close to the Fe-NHis bond distances (1.98 Å) of the 3-His triad in the resting state of the enzyme, as obtained by EXAFS studies. The diketonate substrate-adduct complexes [Fe(L)(acacR)](SO3CF3) (R = Me, Ph) of 1-3 have been obtained using Na(acacR) in acetonitrile. The Fe2+/3+ redox potentials of the complexes (1.05 to 1.2 V vs. Fc/Fc+) and their substrate adducts (1.02 to 1.19 V vs. Fc/Fc+) appeared at almost the same redox barrier. All diketonate adducts exhibit two Fe(ii) → acac MLCT bands around 338 to 348 and 430 to 490 nm. Exposure of these adducts to O2 results in the decay of both MLCT bands with a rate of (kO2) 5.37 to 9.41 × 10-3 M-1 s-1. The kO2 values were concomitantly accelerated 20 to 50 fold by the addition of H+ (acetic acid), which nicely models the rate enhancement in the enzyme kinetics by the glutamate residue (Glu98). The oxygenation of the phenyl-substituted adducts yielded benzoin and benzoic acid (40% to 71%) as cleavage products in the presence of H+ ions. Isotope-labeling experiments using 18O2 showed 47% incorporation of 18O in benzoic acid, which reveals that the oxygen originates from dioxygen. Thus, the present model complexes exhibit very similar chemical surroundings to the active site of DKDO and mimic its functions elegantly. On the basis of these results, the C-C bond cleavage reaction mechanism is discussed.

Exploring Inner-Sphere Water Interactions of Fe(II) and Co(II) Complexes of 12-Membered Macrocycles To Develop CEST MRI Probes.

Several paramagnetic Co(II) and Fe(II) macrocyclic complexes were prepared with the goal of introducing a bound water ligand to produce paramagnetically shifted water 1H resonances and for paramagnetic chemical exchange saturation transfer (paraCEST) applications. Three 12-membered macrocycles with amide pendent groups including 1,7-bis(carbamoylmethyl)-1,4,7,10-tetraazacyclodocane (DCMC), 4,7,10-tris(carbamoylmethyl)-,4,7,10-triaza-12-crown-ether (N3OA), and 4,10-bis(carbamoylmethyl)-4,10-diaza-12-crown-ether (NODA) were prepared and their Co(II) complexes were characterized in the solid state and in solution. The crystal structure of [Co(DCMC)]Br2 featured a six-coordinated Co(II) center with distorted octahedral geometry, while [Co(NODA)(OH2)]Cl2 and [Co(N3OA)](NO3)2 were seven-coordinated. The analogous Fe(II) complexes of NODA and NO3A were successfully prepared, but the complex of DCMC oxidized rapidly to the Fe(III) form. Similarly, [Fe(NODA)]2+ oxidized over several days, forming crystals of the Fe(III) complex isolated as the µ-O bridged dimer. Magnetic susceptibility values and paramagnetic NMR spectra of the Fe(II) complexes of NODA and N3OA, as well as Co(II) complexes of DCMC, NODA, and N3OA, were consistent with high spin complexes. CEST peaks ranging from 60 ppm to 70 ppm, attributed to NH groups of the amide pendents, were identified. Variable-temperature 17O NMR spectra of Co(II) and Fe(II) NODA complexes were consistent with rapid exchange of the water ligand with bulk water. Notably, the Co(II) and Fe(II) complexes presented here produced substantial paramagnetic shifts of bulk water 1H resonances, independent of having an inner-sphere water.

A Structural and Functional Model for the Tris-Histidine Motif in Cysteine Dioxygenase.

The iron(II) complexes [Fe(L)(MeCN)3 ](SO3 CF3 )2 (L are two derivatives of tris(2-pyridyl)-based ligands) have been synthesized as models for cysteine dioxygenase (CDO). The molecular structure of one of the complexes exhibits octahedral coordination geometry and the Fe-Npy bond lengths [1.953(4)-1.972(4) Å] are similar to those in the Cys-bound FeII -CDO; Fe-NHis : 1.893-2.199 Å. The iron(II) centers of the model complexes exhibit relatively high FeIII/II redox potentials (E1/2 =0.988-1.380 V vs. ferrocene/ferrocenium electrode, Fc/Fc+ ), within the range for O2 activation and typical for the corresponding nonheme iron enzymes. The reaction of in situ generated [Fe(L)(MeCN)(SPh)]+ with excess O2 in acetonitrile (MeCN) yields selectively the doubly oxygenated phenylsulfinic acid product. Isotopic labeling studies using 18 O2 confirm the incorporation of both oxygen atoms of O2 into the product. Kinetic and preliminary DFT studies reveal the involvement of an FeIII peroxido intermediate with a rhombic S= 1 / 2 FeIII center (687-696 nm; g≈2.46-2.48, 2.13-2.15, 1.92-1.94), similar to the spectroscopic signature of the low-spin Cys-bound FeIII CDO (650 nm, g≈2.47, 2.29, 1.90). The proposed FeIII peroxido intermediates have been trapped, and the O-O stretching frequencies are in the expected range (approximately 920 and 820 cm-1 for the alkyl- and hydroperoxido species, respectively). The model complexes have a structure similar to that of the enzyme and structural aspects as well as the reactivity are discussed.

Coordination geometry-induced optical imaging of l-cysteine in cancer cells using imidazopyridine-based copper(ii) complexes.

Overexpression of cysteine cathepsins proteases has been documented in a wide variety of cancers, and enhances the l-cysteine concentration in tumor cells. We report the synthesis and characterization of copper(ii) complexes [Cu(L1)2(H2O)](SO3CF3)2, 1, L1 = 3-phenyl-1-(pyridin-2-yl)imidazo[1,5-a]pyridine, [Cu(L2)2(SO3CF3)]SO3CF3, 2, L2 = 3-(4-methoxyphenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine, [Cu(L3)2(H2O)](SO3CF3)2, 3, L3 = 3-(3,4-dimethoxy-phenyl)-1-pyridin-2-yl-imidazo[1,5-a]pyridine and [Cu(L4)2(H2O)](SO3CF3)2, 4, L4 = dimethyl-[4-(1-pyridin-2-yl-imidazo[1,5-a]pyridin-3-yl)phenyl]amine as 'turn-on' optical imaging probes for l-cysteine in cancer cells. The molecular structure of complexes adopted distorted trigonal pyramidal geometry (τ, 0.68-0.87). Cu-Npy bonds (1.964-1.989 Å) were shorter than Cu-Nimi bonds (2.024-2.074 Å) for all complexes. Geometrical distortion was strongly revealed in EPR spectra, showing g‖ (2.26-2.28) and A‖ values (139-163 × 10-4 cm-1) at 70 K. The d-d transitions appeared around 680-741 and 882-932 nm in HEPES, which supported the existence of five-coordinate geometry in solution. The Cu(ii)/Cu(i) redox potential of 1 (0.221 V vs. NHE) was almost identical to that of 2 and 3 but lower than that of 4 (0.525 V vs. NHE) in HEPES buffer. The complexes were almost non-emissive in nature, but became emissive by the interaction of l-cysteine in 100% HEPES at pH 7.34 via reduction of Cu(ii) to Cu(i). Among the probes, probe 2 showed selective and efficient turn-on fluorescence behavior towards l-cysteine over natural amino acids with a limit of detection of 9.9 × 10-8 M and binding constant of 2.3 × 105 M-1. The selectivity of 2 may have originated from a nearly perfect trigonal plane adopted around a copper(ii) center (∼120.70°), which required minimum structural change during the reduction of Cu(ii) to Cu(i) while imaging Cys. The other complexes, with their distorted trigonal planes, required more reorganizational energy, which resulted in poor selectivity. Probe 2 was employed for optical imaging of l-cysteine in HeLa cells and macrophages. It exhibited brighter fluorescent images by visualizing Cys at pH 7.34 and 37 °C. It showed relatively less toxicity for these cell lines as ascertained by the MTT assay.

Nickel(ii) complexes of a 3N ligand as a model for diketone cleaving unusual nickel(ii)-dioxygenase enzymes.

Diketone substrate bound nickel(ii) complexes of 2,6-bis(1-methylbenzimidazolyl)pyridine have been synthesized and characterized as relevant active site models for unusual diketone cleaving Ni(ii)-dependent enzymes Ni-ARD and DKDO. The average Ni-Npy/benzim bond distances (2.050-2.107 Å) of model complexes are almost identical to the Ni-NHis bond distances of NiII-ARD (2.02-2.19 Å). The reaction of these adducts with dioxygen exhibited C-C cleavage with the rate of kO2, 5.24-73.71 × 10-3 M-1 s-1. The phenyl substituted adduct regioselectively elicits 52% of benzoic acid as the major product.

Catalytic fixation of atmospheric carbon dioxide by copper(ii) complexes of bidentate ligands.

New copper(ii) complexes, [Cu(L1)2(H2O)](ClO4)2, 1 [L1 = 2-pyridin-2-yl-quinoline], [Cu(L2)2(H2O)](ClO4)2, 2 [L2 = 2-pyridin-2-yl-quinoxaline], [Cu(L3)2(H2O)](ClO4)2, 3 [L3 = 6,7-dimethyl-2-pyridin-2-yl-quinoxaline], [Cu(L4)2(H2O)](ClO4)2, 4 [L4 = 4-phenyl-2-pyridin-2-yl-quinoline] and [Cu(L5)2(H2O)](ClO4)2, 5 [L5 = 4-phenyl-2-pyridin-2-yl-quinazoline], were synthesized and characterized as catalysts for selective fixation of atmospheric CO2. The molecular structure of 2 was determined by single-crystal X-ray studies and shown to have an unusual trigonal bipyramid geometry (τ, 0.936) around the copper(ii) center, with the coordination of two ligand units and a water molecule. The Cu-Nquin (2.040, 2.048 Å) bonds are slightly longer than the Cu-Npyr (1.987 Å) bonds but shorter than the Cu-Owater bond (2.117 Å). Well-defined Cu(ii)/Cu(i) redox potentials of around 0.352 to 0.401 V were observed for 1-5 in acetonitrile. The electronic absorption spectra of 1-5 showed ligand-based transitions at around 208-286 nm with a visible shoulder at around 342-370 nm. The d-d transitions appeared at around 750-800 and 930-955 nm in acetonitrile. The rhombic EPR spectra of 1-5 exhibited three different g values gx, 2.27-2.34; gy, 2.06-2.09; and gz, 1.95-1.98 at 70 K. Atmospheric CO2 was successfully fixed by 1-5 using Et3N as a sacrificial reducing agent, resulting in CO32--bound complexes of type [Cu(L)CO3(H2O)] that display an absorption band at around 614-673 nm and a νst at 1647 cm-1. This CO32--bound complex of 1 was crystallized from the reaction mixture and it displayed a distorted square pyramidal geometry (τ, 0.369) around the copper(ii) center via the coordination of only one ligand unit, a carbonate group, and water molecules. Furthermore, treatment of the carbonate-bound Cu(ii) complexes with one equivalent of H+ under N2 atmosphere resulted in the liberation of bicarbonate (HCO3-) and regenerated the parent complexes. These regenerated catalysts were active enough to fix CO2 in eight repeating cycles without any change in efficiency. The fixation of CO2 possibly occurs via the formation of Cu(i)-species, which is accompanied by the formation of an MLCT band at around 450-500 nm. The rates of Cu(i)-species formation, kobs, were determined and found to be 5.41-10.31 × 10-3 s-1 in the presence of Et3N in acetonitrile at 25 °C. Interestingly, the copper(i)-species of 3 has been successfully crystallized and displayed a distorted tetrahedral geometry through the coordination of two units of ligand L3.

Copper(ii)-benzimidazole complexes as efficient fluorescent probes for l-cysteine in water.

Copper(ii) complexes [Cu(L1)(H2O)2](SO3CF3)21 and [Cu(L2)(H2O)2](SO3CF3)22 based on 2,6-bis(benzimidazolyl)pyridine were synthesized and are reported herein as highly selective "turn-on" optical probes for l-cysteine. The Cu(ii)/Cu(i) redox potential of probe 1 (0.14 V vs. NHE) was lower than that of 2 (0.233 V vs. NHE) in water. The molecular structure of 2 adopted a square pyramidal geometry (τ = 0.2545), with the Cu-Npy bond (1.958 Å) of its middle pyridine unit being shorter than the other two Cu-Nbenzim bonds (Cu-N, 1.995, 2.000 Å). The axial Cu-O2 bond distance (2.247 Å) was slightly longer than the equatorial Cu-O1 bond distance (1.953 Å). The square-based geometry was further supported by the A∥ value of 156 × 10-4 cm-1 in EPR at 70 K. The d-d and ligand-based transitions appeared at 662 and 314-356 nm for 1 and 651 and 313-360 nm for 2, respectively, in HEPES buffer at pH 7.34. These probes showed selective and efficient "turn-on" fluorescence behaviour towards Cys over other natural amino acids with a binding constant for 1 of 5.4 × 104 and 1.30 × 104 M-1 for 2 and a limit of detection of 2.9 × 10-8 M and 3.32 × 10-8 M, respectively, for 1 and 2 at pH 7.34. The quantum yield for the detection of Cys by 1 (14.7%) was much lower than by 2 (23%). The fluorescence intensity of 1 and 2 were also slightly enhanced by histidine, but at a relatively lower level than that exhibited by Cys.

Nickel(II) complexes of tripodal 4N ligands as catalysts for alkane oxidation using m-CPBA as oxidant: ligand stereoelectronic effects on catalysis.

Several mononuclear Ni(II) complexes of the type [Ni(L)(CH(3)CN)(2)](BPh(4))(2) 1-7, where L is a tetradentate tripodal 4N ligand such as N,N-dimethyl-N',N'-bis(pyrid-2-ylmethyl)ethane-1,2-diamine (L1), N,N-diethyl-N',N'-bis(pyrid-2-ylmethyl)ethane-1,2-diamine (L2), N,N-dimethyl-N'-(1-methyl-1H-imidazol-2-ylmethyl)-N'-(pyrid-2-ylmethyl)ethane-1,2-diamine (L3), N,N-dimethyl-N',N'-bis(1-methyl-1H-imidazol-2-ylmethyl)ethane-1,2-diamine (L4), N,N-dimethyl-N',N'-bis(quinolin-2-ylmethyl)ethane-1,2-diamine (L5), tris(benzimidazol-2-ylmethyl)amine (L6) and tris(pyrid-2-ylmethyl)amine (L7), have been isolated and characterized using CHN analysis, UV-Visible spectroscopy and mass spectrometry. The single-crystal X-ray structures of the complexes [Ni(L1)(CH(3)CN)(H(2)O)](ClO(4))(2) 1a, [Ni(L2)(CH(3)CN)(2)](BPh(4))(2) 2, [Ni(L3)(CH(3)CN)(2)](BPh(4))(2) 3 and [Ni(L4)(CH(3)CN)(2)](BPh(4))(2) 4 have been determined. All these complexes possess a distorted octahedral coordination geometry in which Ni(II) is coordinated to four nitrogen atoms of the tetradentate ligands and two CH(3)CN (2, 3, 4) or one H(2)O and one CH(3)CN (1a) are located in cis positions. The Ni-N(py) bond distances (2.054(2)-2.078(3) Å) in 1a, 2 and 3 are shorter than the Ni-N(amine) bonds (2.127(2)-2.196(3) Å) because of sp(2) and sp(3) hybridizations of the pyridyl and tertiary amine nitrogens respectively. In 3 the Ni-N(im) bond (2.040(5) Å) is shorter than the Ni-N(py) bond (2.074(4) Å) due to the stronger coordination of imidazole compared with the pyridine donor. In dichloromethane/acetonitrile solvent mixture, all the Ni(ii) complexes possess an octahedral coordination geometry, as revealed by the characteristic ligand field bands in the visible region. They efficiently catalyze the hydroxylation of alkanes when m-CPBA is used as oxidant with turnover number (TON) in the range of 340-620 and good alcohol selectivity for cyclohexane (A/K, 5-9). By replacing one of the pyridyl donors in TPA by a weakly coordinating -NMe(2) or -NEt(2) donor nitrogen atom the catalytic activity decreases slightly with no change in the selectivity. In contrast, upon replacing the pyridyl nitrogen donor by the strongly σ-bonding imidazolyl or sterically demanding quinolyl/benzimidazolyl nitrogen donor, both the catalytic activity and selectivity decrease, possibly due to destabilization of the intermediate [(4N)(CH(3)CN)Ni-O˙](+) radical species. Adamantane is selectively (3°/2°, 12-17) oxidized to 1-adamantanol, 2-adamantanol and 2-adamantanone while cumene is selectively oxidized to 2-phenyl-2-propanol. In contrast to cyclohexane oxidation, the incorporation of sterically hindering quinolyl/benzimidazolyl donors around Ni(ii) leads to a high 3°/2° bond selectivity for adamantane oxidation. A linear correlation between the metal-ligand covalency parameter (ß) and the turnover number has been observed.

Faster oxygen atom transfer catalysis with a tungsten dioxo complex than with its molybdenum analog.

The synthesis and characterization of a series of molybdenum ([MoO(2)Cl(L(n))]; L(1) (1), L(2) (3)) and tungsten ([WO(2)Cl(L(n))]; L(1) (2), L(2) (4)) dioxo complexes (L(1) = 1-methyl-4-(2-hydroxybenzyl)-1,4-diazepane and L(2) = 1-methyl-4-(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diazepane) of tridentate aminomonophenolate ligands HL(1) and HL(2) are reported. The ligands were obtained by reductive amination of 1-methyl-1,4-diazepane with the corresponding aldehyde. Complexes 3 and 4 were obtained by the reaction of [MO(2)Cl(2)(dme)(n)] (M = Mo, n = 0; W, n = 1) with the corresponding ligand in presence of a base, whereas for the preparation of 1 and 2 the ligands were deprotonated by KH prior to the addition to the metal. They were characterized by NMR and IR spectroscopy, by cyclic voltammetry, mass spectrometry, elemental analysis and by single-crystal X-ray diffraction analysis. Solid-state structures of the molybdenum and tungsten cis-dioxo complexes reveal hexa-coordinate metal centers surrounded by two oxo groups, a chloride ligand and by the tridentate monophenolate ligand which coordinates meridionally through its [ONN] donor set. In the series of compounds 1-4, complexes 3 and 4 have been used as catalysts for the oxygen atom transfer reaction between dimethyl sulfoxide (DMSO) and trimethyl phosphine (PMe(3)). Surprisingly, faster oxygen atom transfer (OAT) reactivity has been observed for the tungsten complex [WO(2)Cl(L(2))] (4) in comparison to its molybdenum analog [MoO(2)Cl(L(2))] (3) at room temperature. The kinetic results are discussed and compared in terms of their reactivity.

Mechanistic insight into the reactivity of oxotransferases by novel asymmetric dioxomolybdenum(VI) model complexes.

The asymmetric molybdenum(VI) dioxo complexes of the bis(phenolate) ligands 1,4-bis(2-hydroxybenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-4-methylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-3,5-dimethylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-4-flurobenzyl)-1,4-diazepane, and 1,4-bis(2-hydroxy-4-chlorobenzyl)-1,4-diazepane (H(2)(L1)-H(2)(L6), respectively) have been isolated and studied as functional models for molybdenum oxotransferase enzymes. These complexes have been characterized as asymmetric complexes of type [MoO(2)(L)] 1-6 by using NMR spectroscopy, mass spectrometry, elemental analysis, and electrochemical methods. The molecular structures of [MoO(2)(L)] 1-4 have been successfully determined by single-crystal X-ray diffraction analyses, which show them to exhibit a distorted octahedral coordination geometry around molybdenum(VI) in an asymmetrical cis-ß configuration. The Mo-O(oxo) bond lengths differ only by ≈0.01 Å. Complexes 1, 2, 5, and 6 exhibit two successive Mo(VI)/Mo(V) (E(1/2), -1.141 to -1.848 V) and Mo(V)/Mo(IV) (E(1/2), -1.531 to -2.114 V) redox processes. However, only the Mo(VI)/Mo(V) redox couple was observed for 3 and 4, suggesting that the subsequent reduction of the molybdenum(V) species is difficult. Complexes 1, 2, 5, and 6 elicit efficient catalytic oxygen-atom transfer (OAT) from dimethylsulfoxide (DMSO) to PMe(3) at 65 °C at a significantly faster rate than the symmetric molybdenum(VI) complexes of the analogous linear bis(phenolate) ligands known so far to exhibit OAT reactions at a higher temperature (130 °C). However, complexes 3 and 4 fail to perform the OAT reaction from DMSO to PMe(3) at 65 °C. DFT/B3LYP calculations on the OAT mechanism reveal a strong trans effect.