Linkage Isomers Research Articles

Investigation of nitro-nitrito photoisomerization: crystal structure of trans-chlorido-nitro-(1,4,8,11-tetra-aza-cyclo-tetra-decane-κ4 N,N',N'',N''')cobalt(III) chloride.

The reaction cavity of the nitro group in the crystal of the title compound, [CoCl(NO2)(C10H24N4)]Cl, (I), was investigated to confirm that it offers sufficient free space for linkage isomerization to occur in accordance with the observed photochemical reactivity. The complex cation has crystallographic 2/m symmetry and the nitro and chloro ligands at the trans positions are statistically disordered. The complete cyclam ligand is generated by symmetry from a quarter of the mol-ecule. In the crystal of (I), the complex cations and Cl- ions are linked into a three-dimensional network by N-H⋯Cl(counter-ion) hydrogen bonds.

Ruthenium(II) p-cymene complexes bearing 2‑(1,2,4‑triazol‑3‑yl)pyridines: Linkage isomerism and related NMR/DFT studies

A series of ruthenium(II) p-cymene complexes bearing 2‑(1,2,4‑triazol‑3‑yl)pyridines was obtained. A simple and efficient 1H NMR spectroscopic criterion for determining coordination mode of the 2‑(1,2,4‑triazol‑3‑yl)pyridines as ligands in the complexes is described. The validity of the criterion is corroborated by DFT calculations using B3LYP functional and mixed LANL2DZ/6-31**G basis set. Also, the influence of the size of the substituent in 5-position of the triazole ring on linkage isomers' ratio is discussed.

Rapid discrimination and quantification of isomeric flavonoid-O-diglycosides in Citrus paradisi cv. changshanhuyou by online extraction–quadrupole time-of flight tandem mass spectrometry

Rapid differentiation, characterization and quantification of isomers from complex mixtures by direct mass spectrometry (MS) remained an analytical challenge due to their similar or identical MS/MS spectra and matrix interferences. Here, we reported a novel online extraction–quadrupole time-of-flight tandem mass spectrometry (OLE–QTOF-MS/MS) system to rapid, efficient and sensitive analysis of interglycosidic linkage isomers (hesperidin and neohesperidin) in Citrus paradisi cv. Changshanhuyou (Changshanhuyou). OLE system packed with solid Changshanhuyou (0.02 mg) could be firstly used to online remove interferences with large polarities, and then online extract and enrich hesperidin and neohesperidin, which shows great potential to diminish the analysis time of sample pretreatment, as well as to reduce matrix effects and instrument consumption. Detailed fragmentation analysis found that, under positive ion mode, relative abundance of specific fragment ions m/z 449 to m/z 303 showed linear correlation to the mass content of hesperidin (0% to 100%) with good correlation coefficient (R2 = 0.9958). Utilizing this method, the mass ratio of hesperidin to neohesperidin in Changshanhuyou was relatively quantified as 3.7:96.3 with RSD at 2.9%. Finally, using internal standard method, the absolute quantitative analysis was performed with acceptable reproducibility (RSD 1.3 and 4.5% for intra- and inter-day variations) and recoveries (from 95.9% to 108.9%), acceptable limit of detection (0.33 ng). In general, OLE–QTOF-MS/MS represented a promising and practical method for simple, rapid and effective analysis of isomeric compounds in complex matrices.

Fac-99mTc/Re-tricarbonyl complexes with tridentate aminocarboxyphosphonate ligands: Suitability of the phosphonate group in chelate ligand design of new imaging agents

Ligands that coordinate via dianionic phosphonate groups have not been widely utilized in radiopharmaceuticals. N-(phosphonomethyl)iminodiacetic acid (1, PMIDA) and N-(phosphonomethyl)glycine (2, PMG) were investigated as new chelators for the 99mTc/Re-tricarbonyl “core” (fac-M(CO)3, M = 99mTc, Re) present in a major class of radiopharmaceuticals.fac-M(CO)3(PMIDA) and fac-M(CO)3(PMG) complexes were studied by HPLC and 1H/13C/31P NMR methods for M = Re (Re-1 and Re-2) and by HPLC for M = 99mTc (99mTc-1 and 99mTc-2). Re-1 and 99mTc-1 complexes exhibit a similar pH-dependent equilibrium between geometric linkage isomers (M-1a and M-1b). However, only one isomer exists for M-2 under all conditions. Structural characterization by X-ray crystallography reveals the presence of a bond between a phosphonate oxygen and the Re(I) center in fac-Re(CO)3(PMG) (Re-2). Detailed comparisons of NMR data for Re-2 conclusively demonstrate that the phosphonate group is coordinated in Re-1b (isomer favored at high pH) but not in Re-1a, which has a dangling N-(phosphonomethyl) group. To our knowledge, Re-1b and Re-2 and their 99mTc analogs are the first well-documented examples of complexes with these metal-tricarbonyl cores having a dianionic phosphonate group directly coordinated in a fac-M(CO)3-O-P grouping. Pharmacokinetic studies using Sprague-Dawley rats reveal that 99mTc-2 is a robust tracer. Hence, phosphonate groups should be considered in designing 99mTc and 186/188Re radiopharmaceuticals, including agents with bioactive moieties attached to dangling carboxylate or phosphonate groups.

Structural insights into cGAMP degradation by Ecto-nucleotide pyrophosphatase phosphodiesterase 1

ENPP1 (Ecto-nucleotide pyrophosphatase phosphodiesterase 1), a type II transmembrane glycoprotein, hydrolyzes ATP to produce AMP and diphosphate, thereby inhibiting bone mineralization. A recent study showed that ENPP1 also preferentially hydrolyzes 2′3′-cGAMP (cyclic GMP-AMP) but not its linkage isomer 3′3′-cGAMP, and negatively regulates the cGAS-STING pathway in the innate immune system. Here, we present the high-resolution crystal structures of ENPP1 in complex with 3′3′-cGAMP and the reaction intermediate pA(3′,5′)pG. The structures revealed that the adenine and guanine bases of the dinucleotides are recognized by nucleotide- and guanine-pockets, respectively. Furthermore, the structures indicate that 2′3′-cGAMP, but not 3′3′-cGAMP, binds to the active site in a conformation suitable for catalysis, thereby explaining the specific degradation of 2′3′-cGAMP by ENPP1. Our findings provide insights into how ENPP1 hydrolyzes both ATP and cGAMP to participate in the two distinct biological processes.

Mechanistic Insights into the Stepwise Assembly of Ruthenium(II) Tris-heteroleptic Compounds

The ruthenium(II) tris-heteroleptic compounds cis-[Ru(NN)(dcbH2)(NCS)2], NN = polypyridyl ligand and dcbH2 = 2,2'-bipyridine-4,4'-dicarboxylic acid, can be synthesized by a one-pot route starting from [Ru( p-cymene)Cl2]2, followed by the sequential addition of ligands. In this work, each synthetic step for the cis-[Ru(R-phen)(dcbH2)(NCS)2] (R = H, Me, Ph, MeO, or Cl) preparation was individually investigated, aiming to identify reaction intermediates and to establish correlations among temperature, reaction time, reactant concentration, and the identity of the substituent of the polypyridyl ligand with the kinetics of the reactions and distribution of the products. The first step is the cleavage of [Ru( p-cymene)Cl2]2, followed by the coordination of R-phen via an associative mechanism and establishment of a direct correlation between the electron-donating or electron-withdrawing character of R and the reaction rates. The second step is the conversion of [Ru(R-phen)( p-cymene)Cl]Cl to cis-[Ru(R-phen)(dcbH2)Cl2], and the rate-determining step is the formation of the intermediate [Ru(R-phen)Cl2], which exhibits a low dependence on R. The last step is the substitution of Cl- by NCS-, and the N-bound isomer is the major product. The reaction temperature, time, and identity of R influence the relative distribution of the linkage isomers. The comprehension of each of these processes is a key factor to develop new strategies to optimize the one-pot synthetic route.

Three Isomers in Equilibrium: Phosphine Exchange of Coordinated and Pendant Phosphines in a Unique Complex, (OC)5WL (L = 1,2-Bis(diphenylphosphino)-1-di-p-tolylphosphinoethane), and Implications for Understanding the k2 Term in the Rate Law for Phosphine Substitution in Group 6 Metal Carbonyl Complexes

The linkage isomers [(OC)5W{κ1-PPh2CH2CH(PPh2)[P(p-tol)2]}] 3a, [(OC)5W{κ1-P(p-tol)2CH(PPh2)CH2PPh2}] 3b, and [(OC)5W{κ1-PPh2CH[P(p-tol)2]CH2PPh2}] 3c isomerize at ambient temperatures to give a mixture of the three isomers in equilibrium. Rates of isomerization and equilibrium constants have been measured at temperatures from 10 to 55 °C, and from these, enthalpies and entropies have been determined. The isomerization reactions are initiated by a nucleophilic attack of a pendant phosphine on a bound carbonyl group followed by dissociation of a coordinated phosphine. These studies lead us to suggest that the k2 term in the rate law for CO replacement by phosphines is based on a similar mechanism and offers a plausible clarification of the currently accepted understanding. The crystal structure of 3b, the most stable of the three isomers, has been determined.

Identification of sialic acid linkage isomers in glycans using coupled InfraRed Multiple Photon Dissociation (IRMPD) spectroscopy and mass spectrometry

The gas phase IR spectra of α2,3 and α2,6 linkage isomers of sialic acid-containing human milk oligosaccharides and N-glycans epitopes are measured in the 3 µm spectral range using IRMPD spectroscopy in protonated and Na+ charge states. Each linkage isomer has a unique IRMPD fingerprint, providing a convenient diagnostic of the sialic acid position. Finally, a generic trend is observed: 3-linked sialic acid results in a significant broadening of the spectroscopic signature regardless of the glycan core and the charge state which suggests a drastic influence of the sialic acid position on the glycan conformation.

Synthesis, structure and properties of (NH4)2[RuNO(NO2)4OH] and NH4[RuNO(L)(NO2)3OH] (L=NH3, Py)

The ammonium salt (NH4)2[RuNO(NO2)4OH] was prepared, characterized by thermogravimetric analysis, IR spectroscopy and its molecular and crystal structures were determined. Heating of the salt was investigated in organic solvents (pyridine and acetonitrile) using 15N-NMR spectroscopy and the reaction led to the preparation of the [RuNO(NO2)3(Py)OH]- anion with good yield (60%). Crystal structures of the two products (NH4)[RuNO(NO2)3(Py)OH] and NH4[RuNO(NO2)3(NH3)OH] were determined. Both (NH4)2[RuNO(NO2)4OH] and (NH4)[RuNO(NO2)3(Py)OH] underwent photo-induced (445 nm) linkage isomerization (RueNO to Ru–ON) but the population of the metastable isomer did not exceed 5–7%.

Theoretical Study of the Solvent Effect on the Electronic and Vibrational Properties of [CpFe(CO)2(NCS)] and [CpFe(CO)2(SCN)] Linkage Isomers

The present study illustrates the stability of [CpFe(CO)2(NCS)] and [CpFe(CO)2(SCN)] linkage isomers by the use of MPW1PW91 quantum method in the gas and solution phases. Our results reveal that the [CpFe(CO)2(NCS)] isomer is more stable than the [CpFe(CO)2(SCN)] isomer. Based on the polarizable continuum model, the effect of the solvent polarity on the stability, structural parameters, frontier orbital energies, and vibrational modes of carbonyl ligands (νCO) of these linkage complexes is explored. The molecular orbital analysis suggests that the major contributions to HOMO and LUMO arise from the ambidentate ligand and Fe in two isomers, respectively. In addition, the bonding interaction between the CpFe(CO)2 fragment and the ambidentate ligand is studied by means of the energy decomposition analysis. The back-bonding effect in Fe–CO bonds is revealed in the calculation of the quadrupole polarization of the carbon atom by the QTAIM analysis. The character of Fe–N and Fe–S bonds in these complexes is analyzed by the natural bond orbital analysis.

Theoretical Studies of Solvent Effect on the Structure, Вonding, and Spectroscopic Рroperties (IR, NMR) in the cis-[Pt(PH3)2(NCS)2] and [Pt(PH3)2(SCN)2] Linkage Isomers

The present investigation explores the stability of linkage isomers of cis-[Pt(PH3)2(NCS)2] and [Pt(PH3)2(SCN)2] by the use of MPW1PW91 quantum method. The polarity of solvent effect on dipole moment, structural parameters, and electronic properties, spectroscopic properties (IR and NMR) was studied. The selected vibrations of IR-active in different solvents were obtained and correlated with Kirkwood–Bauer–Magat equation (KBM). The d-orbitals energies of platinum were calculated by NBO analysis. It was seen good correlation were obtained between 195Pt chemical shifts and the spectral parameters obtained from the energies of electronic transitions between Pt d-orbitals in the cis-[Pt(PH3)2(NCS)2] complex. Also, 1J(Pt–N) values were correlated with Pt–N distances.

Enzymatic Cascade Synthesis Provides Novel Linear Human Milk Oligosaccharides as Reference Standards for xCGE-LIF Based High-Throughput Analysis.

A rising amount of known health benefits leads to an increased attention of science and nutrient industry to human milk oligosaccharides (HMOS). The unique diversity of HMOS includes several rare, complex, and high molecular weight structures. Therefore, identification and elucidation of complex structures, which may occur only in traces, poses a daunting analytical challenge, further complicated by the limited access to suitable standards. Regarding this, inherent diversity of HMOS and their structural complexity make them difficult to synthesize. The use of recombinant Leloir-glycosyltransferases offers a common strategy to overcome the latter issues. In this study, linear long-chained Lacto-N-biose-type (LNT) and Lacto-N-neo-type (LNnT) HMOS are tailored far beyond the known naturally occurring length. Thereby novel well-defined reference standards for screening HMOS composition by high performance and high throughput analytics are provided. It is shown here for the first time the synthesis of LNT oligomers up to 26 and LNnT oligomers up to 30 sugar units in a semi-sequential one-pot synthesis as analyzed by high performance multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF). While being a high-throughput method, xCGE-LIF can also handle long chained linkage isomers of challenging similarity, some of them even present only in trace amounts.

Watching chemistry happen – dynamic studies of light-induced transformations in linkage isomerism complexes

Watching chemistry happen – dynamic studies of light-induced transformations in linkage isomerism complexes

Cyanide Docking and Linkage Isomerism in Models for the Artificial [FeFe]-Hydrogenase Maturation Process.

Linkage isomerization of the cyanide on the [2Fe] subsite of the [FeFe]-H2ase active site was reported to occur during the docking of various synthetic diiron complexes onto a carrier protein, apo-HydF, as the initial step for the artificial maturation of the [FeFe]-H2ase enzyme (Berggren et al., Nature, 2013, 499, 66-70). An investigation of our triiron organometallic models (FeFe-CN/NC-Fe') revealed that, once a Fe-CN-Fe connection is formed, high barriers prevent such cyanide linkage isomerization ( Chem. Sci., 2016, 7, 3710-3719). To explore effects of variable oxidation states of the receiver unit, we introduce copper(I/II) fragments, precedented in Holm's models of cytochrome c oxidase to induce cyanide isomerization (Cu-CN/NC-Fe), to the diiron synthetic analogues of [FeFe]-H2ase. For comparison, a zinc variant of the cytochrome c oxidase model is also examined. According to the oxidation state of copper, a cyanide flip was induced during the formation of both Zn-NC-Cu and FeFe-CN-Cu complexes. Density functional theory calculations are used to predict the mechanisms for such linkage isomerization and account for optimal conditions including oxidation states of metals, spin states, and solvation. These results on synthetic paradigms imply a role for oxidation state control of cyanide isomerization during hydrogenase active site assembly.

Probing the dynamics of dithiooxamide coordinated to gold nanoparticles using SERS

AbstractThe substitution kinetics and specific binding modes of the dithiooxamide (dto) ligand at the metal surface have been investigated and interpreted on the light of theoretical and experimental Raman studies. By monitoring the vibrational properties of this ligand, it was shown that gold nanoparticles employed as surface‐enhanced effects (SERS) probes are strongly dependent on the coordination chemistry of the ligands at the metal interface. The binding of dto to the gold nanoparticles led to linkage isomers, and at low concentrations, the bidentate form, corresponding to bis‐thione‐Au bond in cis configuration {Au‐S(NH2)CC(NH2)S‐Au}, was the predominating species. Even at high concentrations, the cis‐configuration was observed first; but as the ligand competition dynamics proceeded, the binding mode gradually changed into a monodentate thione‐Au mode {AuS(NH2)CCS(NH2)}. In this mode, the dto ligand adopts a thermodynamically favorable trans‐conformation geometry, producing dramatic changes in the SERS spectra. Such dynamic behavior of the ligand at the metal plasmonic surface is of crucial importance, as one of the possible factors associated with lack of reproducibility of the SERS spectra frequently reported in the literature.

Transient metal-centered states mediate isomerization of a photochromic ruthenium-sulfoxide complex

Ultrafast isomerization reactions underpin many processes in (bio)chemical systems and molecular materials. Understanding the coupled evolution of atomic and molecular structure during isomerization is paramount for control and rational design in molecular science. Here we report transient X-ray absorption studies of the photo-induced linkage isomerization of a Ru-based photochromic molecule. X-ray spectra reveal the spin and valence charge of the Ru atom and provide experimental evidence that metal-centered excited states mediate isomerization. Complementary X-ray spectra of the functional ligand S atoms probe the nuclear structural rearrangements, highlighting the formation of two metal-centered states with different metal-ligand bonding. These results address an essential open question regarding the relative roles of transient charge-transfer and metal-centered states in mediating photoisomerization. Global temporal and spectral data analysis combined with time-dependent density functional theory reveals a complex mechanism for photoisomerization with atomic details of the transient molecular and electronic structure not accessible by other means.

Linkage Photoisomerization of an Isolated Ruthenium Sulfoxide Complex: Sequential versus Concerted Rearrangement.

Ruthenium sulfoxide complexes undergo thermally reversible linkage isomerization of sulfoxide ligands from S- to O-bound in response to light. Here, we report photoisomerization action spectra for a ruthenium bis-sulfoxide molecular photoswitch, [Ru(bpy)2(bpSO)]2+, providing the first direct evidence for photoisomerization of a transition metal complex in the gas phase. The linkage isomers are separated and isolated in a tandem drift tube ion mobility spectrometer and exposed to tunable laser radiation provoking photoisomerization. Direct switching of the S,S-isomer to the O,O-isomer following absorption of a single photon is the predominant isomerization pathway in the gas phase, unlike in solution, where stepwise isomerization is observed with each sulfoxide ligand switching in turn. The change in isomerization dynamics is attributed to rapid vibrational quenching that suppresses isomerization in solution. Supporting electronic structure calculations predict the wavelengths and intensities of the peaks in the photoisomerization action spectra of the S,S- and S,O-isomers, indicating that they correspond to metal-to-ligand charge transfer (MLCT) and ligand-centered ππ* transitions.

Six-Coordinate Nitrato Complexes of Iron Porphyrins with Trans S-Donor Ligands.

The reaction of dimethyl sulfide (DMS) and tetrahydrothiophene (THT) with thin, amorphous layers of the nitrato complexes Fe(Por)(η2-O2NO) (Por = meso-tetraphenylporphyrinato dianion or meso-tetra- p-tolylporphyrinato dianion) at low temperature leads to formation of the corresponding six-coordinate complexes Fe(Por)(L)(η1-ONO2) (L = DMS, THT) as characterized by Fourier transform infrared and optical spectroscopy measurements. Adduct formation was accompanied by bidentate-to-monodentate linkage isomerization of the nitrato ligand, with the FeIII center remaining in a high-spin electronic state. These adducts are thermally unstable; warming to room temperature restores the initial Fe(Por)(η2-O2NO) species.

Tetranuclear Ru 2 Ln 2 complexes of heavier lanthanides (Gd, Tb, Dy, Ho, Lu) with [RuNO(NO 2 ) 4 OH] 2− anion, combining SMM properties and photoswitchable Ru-NO group

Abstract Five new heterometallic complexes with a {Ln[RuNO(µ-NO2)4(µ3-OH)]2Ln} (Ln = Gd, Tb, Dy, Ho, Lu) core were prepared by the reaction of Na2[RuNO(NO2)4OH] with lanthanide nitrates. Investigation of magnetic properties showed that magnetic interactions between lanthanide ions become apparent at temperatures lower than 40–50 K, while at temperatures higher than 100 K the dependencies of magnetic susceptibility of the complexes are well explained by the presence of two non-interacting paramagnetic centres. Frequency dependencies of magnetic susceptibility for the dysprosium complex in the temperature range 10–30 K revealed single molecule magnet (SMM) properties with a thermally activated slow magnetic relaxation process. The anisotropy barrier is 89.4 cm−1 (112 K) and τ0 = 7.6 × 10−7 s. Irradiation of the Dy2Ru2 complex with blue light (443 nm) at 80 K resulted in the formation of nitrosyl linkage isomers of the RuNO fragment; the Td of reverse isomerisation is 195 K.

A biomimetic design for a sialylated, glycan-specific smart polymer

Increasing evidence has indicated that glycans and their interactions with glycan-specific binding proteins have crucial roles in most physiological processes. One emerging topic in biomaterials is the construction of smart materials capable of recognizing and responding to these valuable glycans. However, because of the complicated compositions and structures as well as the low abundances and microheterogeneity of glycans, developing glycan-responsive materials with a high sensitivity and specificity is a long-term, challenging goal. Here, we report a biomimetic polymer capable of capturing and discriminating sialo-complex-type glycans with the core Neu5Ac-Gal-GlcNAc-Man sequence, which is one of the most effective biomarkers for cancer detection. As an optimized dipeptide, L-Asp-L-Phe has a strong but differential binding affinity for N-acetyl-neuraminic acid (Neu5Ac), N-acetyl-glucosamine (GlcNAc), galactose (Gal), and mannose (Man), which are the core construction units of sialylated glycans. In addition, the L-Asp-L-Phe-grafted polyethyleneimine film displays remarkable adsorption behavior for the model sialylated glycans and can discriminate their linkage isomers, which is accompanied by significant changes in the surface morphology and stiffness. These features facilitate the highly selective capture of sialylated glycopeptides from complex protein samples using PEI-g-L-Asp-L-Phe-modified mSiO2@SiO2@Fe3O4 core-shell microspheres. The mechanism analysis demonstrates that the favorable polymeric spatial structures and multiple synergetic hydrogen-bonding interactions among the dipeptides and glycan are the main driving forces, indicating a clear direction for designing glycan-specific biomaterials.