Chemistry Commons^™

The Synthesis Of Angucyclines Using An Intramolecular Bradsher Cycloaddition, Abdullah Allaoa, Tony E. Nicolas

Publications and Research

The Angucyclines are natural products which possess a broad spectrum of biological properties. Of particular interest are the natural products which contain the cis-hydroxyl motif at the AB ring junction. Their synthesis is particularly challenging. Our model study has resulted in the synthesis of a model of the angucyclines with the required cis-hydroxyl features. The present work will apply the previously developed chemistry to an intramolecular version which will lead to the synthesis of the ABC ring system

From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford

Publications and Research

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics …

Titanocene−Gold Complexes Containing N‑Heterocyclic Carbene Ligands Inhibit Growth Of Prostate, Renal, And Colon Cancers In Vitro, Yiu Fung Mui, Jacob FernáNdez-Gallardo, Benelita T. Elie, Ahmed Gubran, Irene Maluenda, Mercedes Sanau, Marıá Contel

Publications and Research

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer …

Discovery And Characterisation Of A Novel Toxin From Dendroaspis Angusticeps, Named Tx7335, That Activates The Potassium Channel Kcsa, Ivan O. Rivera-Torres, Tony B. Jin, Martine Cadene, Brian T. Chait, Sébastien F. Poget

Publications and Research

Due to their central role in essential physiological processes, potassium channels are common targets for animal toxins. These toxins in turn are of great value as tools for studying channel function and as lead compounds for drug development. Here, we used a direct toxin pull-down assay with immobilised KcsA potassium channel to isolate a novel KcsA-binding toxin (called Tx7335) from eastern green mamba snake (Dendroaspis angusticeps) venom. Sequencing of the toxin by Edman degradation and mass spectrometry revealed a 63 amino acid residue peptide with 4 disulphide bonds that belongs to the three-finger toxin family, but with a unique modification …

Glass Polymorphism In Glycerol–Water Mixtures: Ii. Experimental Studies, Johannes Bachler, Violeta Fuentes-Landete, David A. Jahn, Jessina Wong, Nicolas Giovambattista, Thomas Loerting

Publications and Research

We report a detailed experimental study of (i) pressure-induced transformations in glycerol–water mixtures at T = 77 K and P = 0–1.8 GPa, and (ii) heating-induced transformations of glycerol–water mixtures recovered at 1 atm and T = 77 K. Our samples are prepared by cooling the solutions at ambient pressure at various cooling rates (100 K s1–10 K h1) and for the whole range of glycerol mole fractions, wg. Depending on concentration and cooling rates, cooling leads to samples containing amorphous ice (wg Z 0.20), ice (wg r 0.32), and/or ‘‘distorted ice’’ (0 o wg r 0.38). Upon compression, we …

Sulfur-Mediated Photochemical Energy Harvesting In Nanoporous Carbons, Alicia Gomis-Berenguer, Mykola Seredych, Jesus Iniesta, Joao C. Lima, Teresa J. Bandosz, Conchi O. Ania

Publications and Research

This work provides new insights in the field of applied photochemistry based on semiconductor-free nanoporous carbons and its application to sunlight energy harvesting. Using carbon materials of increasing average pore size, chemical functionalization to introduce a variety of O- and S-containing functional groups and monochromatic light, we have shown the dependence of the photochemical conversion of phenol in the confinement of the carbons nanopore space with the wavelength of the irradiation source, the dimensions of the pore voids and their surface chemistry. The photochemical conversion of phenol inside the carbons pore space was found to be very sensitive to the …

Water Condensation And Protein Adsorption On Hybrid Superhydrophobic-Hydrophilic Surfaces, Bikash Mondal

Dissertations, Theses, and Capstone Projects

This thesis describes the study of protein adsorption and water condensation on hybrid superhydrophobic-hydrophilic surfaces for various technological applications such as diagnostics, artificial organs and medical devices, water collection, and heat transfer.

In the chapter 1, a general introduction to wetting theories, superhydrophobic surface, and hybrid surfaces is given. In chapter 2, design and fabrication of a hybrid superhydrophobic surface for studying dropwise condensation and heat transfer is discussed. Effect of surface chemistry and wettability on protein adsorption is discussed in the chapter 3. Finally, in chapter 4, the protein adsorption study on hybrid superhydrophobic surfaces made by 3D-printing and …

Design Rules For The Nucleation, Growth, And Encapsulation Of Gold Nanoparticles With Applications To Cancer Imaging, Matthew A. Wall

Dissertations, Theses, and Capstone Projects

Surface-enhanced Raman scattering (SERS) nanoparticles are exciting candidates for high-precision cancer imaging due to their highly specific spectral signature (Raman “fingerprint”) and propensity for passive targeting of cancerous tissues. However, the signal intensity of currently available SERS nanoparticles is insufficient for cancer imaging via passive targeting in most solid tumors. The overarching aim of this body of work is to develop a new generation of SERS nanoparticles with sufficiently low limits of detection to enable robust detection of various solid tumors in vivo.

The complexity of SERS nanoparticles requires significant advances to the theoretical and experimental understanding of metal …

Ultrafast Spectroscopy And Energy Transfer In An Organic/Inorganic Composite Of Zinc Oxide And Graphite Oxide, Jeff A. Secor

Dissertations, Theses, and Capstone Projects

The energy transfers and nature of defect levels of an organic/inorganic composite of Zinc Oxide and Graphite are studied with multidimensional spectroscopy. The edge and surface states of each composite are uncovered using excitation emission experiments showing which defect states are mediating the energy transfer from the metal oxide to the graphite oxide. Multidimensional time resolved spectroscopy further describes the effect of the carbon phase on the energy transfer pathways in the material.

Synthesis And Characterization Of Segmented Fluorescent Conjugated Polymers Via Acyclic Diene Metathesis (Admet), Gagandeep Singh

Dissertations, Theses, and Capstone Projects

This doctoral thesis is focused on the novel and facile synthesis and characterization of segmented conjugated polymers featuring various electro-optically active segments, with or without heteroatom linkages. The polymers were synthesized, via acyclic diene metathesis (ADMET) using ruthenium-based Grubbs-type catalysts. All products are soluble, and have a well-defined all-trans microstructure without defects. Some of the polymers were also synthesized via Suzuki polycondensation for comparison purposes. All monomers utilized were designed and synthesized in the laboratory.

Segmented conjugated polymers have received a great deal of attention in organic electronics, such as organic light emitting-diodes, organic field-effect transistors and organic solar …

Characterization Of 1, 4, 7-Trithiacyclononane, [9]Anes3 As A Potential Toxic Heavy Metal Chelator, Nahid Bakhtari

Student Theses and Dissertations

Toxic heavy metal poisoning with metals including lead, mercury, and cadmium, whether in the environment or through ingestion, remains a persistent problem. Remediation of metal contamination and poisoning has generally been treated with chelating agents that bind metals, rendering them inert, and allow for easier removal. Chelation involves the formation of two or more separate coordinate covalent bonds between a polydentate ligand and a single central atom. However, chelators are not without side effects. Due to the similar size of metal ions and lack of specificity of ligands, chelators can also remove beneficial metals like iron and zinc from the …

Pore Structure And Synergy In Antimicrobial Peptides Of The Magainin Family, Almudena Pino-Angeles, John M. Leveritt Iii, Themis Lazaridis

Publications and Research

Magainin 2 and PGLa are among the best-studied cationic antimicrobial peptides. They bind preferentially to negatively charged membranes and apparently cause their disruption by the formation of transmembrane pores, whose detailed structure is still unclear. Here we report the results of 5–9 μs all-atom molecular dynamics simulations starting from tetrameric transmembrane helical bundles of these two peptides, as well as their stoichiometric mixture, and the analog MG-H2 in DMPC or 3:1 DMPC/DMPG membranes. The simulations produce pore structures that appear converged, although some effect of the starting peptide arrangement (parallel vs. antiparallel) is still observed on this timescale. The peptides …

Density Functional Investigation Of The Inclusion Of Gold Clusters On A Ch3s Self-Assembled Lattice On Au(111), Darnel J. Allen, Wayne E. Archibald, John A. Harper, John C. Saputo, Daniel Torres

Publications and Research

We employ first-principles density functional theoretical calculations to address the inclusion of gold (Au) clusters in a well-packed CH3S self-assembled lattice. We compute CH3S adsorption energies to quantify the energetic stability of the self-assembly and gold adsorption and dissolution energies to characterize the structural stability of a series of Au clusters adsorbed at the SAM-Au interface. Our results indicate that the inclusion of Au clusters with less than four Au atoms in the SAM-Au interface enhances the binding of CH3S species. In contrast, larger Au clusters destabilize the self-assembly.We attribute this effect to the low-coordinated gold atoms in the cluster. …

Self-Assembly Of Gold Supraparticles With Crystallographically Aligned And Strongly Coupled Nanoparticle Building Blocks For Sers And Photothermal Therapy, S. Paterson, S. A. Thompson, J. Gracie, A. W. Wark, R. De La Rica

Publications and Research

A new method is introduced for self-assembling citrate-capped gold nanoparticles into supraparticles with crystallographically aligned building blocks. It consists in confining gld nanoparticles inside a cellulose acetate membrane. The constituent nanoparticles are in close contact in the superstructure, and therefore generate hot spots leading to intense Surface-Enhanced Raman Scattering (SERS) signals. They also generate more plasmonic heat than the nanoparticle building blocks. The supraparticles are internalized by cells and show low cytotoxicity, but can kill cancer cells when irradiated with a laser. This, along with the improved plasmonic properties arising from their assembly, makes the gold supraparticles promising materials for …

Adsorption Of Antibiotics By Vermiculite, Mosa J. Ferdous

Dissertations and Theses

The occurrence of residual antibiotics in the environment has been a worldwide issue and warrants the development of inexpensive yet effective methods for antibiotics removal from contaminated water. In this thesis work, the adsorption of four antibiotics, namely chlorotetracycline (CTC), oxytetracycline (OTC), ofloxacin (OFL), and enrofloxacin (ENR), onto natural vermiculite has been studied using batch (static) and column (dynamic) adsorption techniques. The Langmuir and Freundlich isotherm models were initially used to explain the adsorption processes. The separation factor (RL) values derived from the Langmuir model and the 1/n values derived from Freundlich model in the present investigation were less than …

Julia-Kocienski Approach To 4-Substituted 1- Alkenyl-1h-1,2,3-Triazoles, Kunga Tsetan

Dissertations and Theses

A modular approach to the synthesis of 4-substituted N-vinyltriazoles was
developed. The triazole cores were assembled by copper-catalyzed 1,3-dipolar
cycloaddition of 1-phenyl-1H-tetrazol-5-yl (PT) azidomethyl sulfide with: pmethoxyphenyl, 2-pyridyl, and triisopropylsilyl alkynes. Subsequent oxidation of the sulfides furnished 4-substituted triazoles with a Julia-Kocienski olefination handle attached at the N1 atom of the triazole. Olefination reactions of triazole-derived Julia-Kocienski reagents with paraformaldehyde gave 1-ethenyl-1H-1,2,3-triazoles. Heck reactions of these products with phenyl or p-methoxyphenyl iodide led to further functionalization of the terminal carbon, with E/Z-olefin ratios ≥ 92%. Heck reaction with p-cyanophenyl iodide gave low conversion, and that with 2-thienyl iodide did not …

Quantitative Model For Rationalizing Solvent Effect In Noncovalent Ch-Aryl Interactions, Bright C. Emenike, Sara N. Bey, Brianna C. Bigelow, Srinivas V.S. Chakravartula

Publications and Research

The strength of CH–aryl interactions (ΔG) in 14 solvents was determined via the conformational analysis of a molecular torsion balance. The molecular balance adopted folded and unfolded conformers in which the ratio of the conformers in solution provided a quantitative measure of ΔG as a function of solvation. While a single empirical solvent parameter based on solvent polarity failed to explain solvent effect in the molecular balance, it is shown that these ΔG values can be correlated through a multiparameter linear solvation energy relationship (LSER) using the equation introduced by Kamlet and Taft. The resulting LSER …

Hybrid Sol–Gel Glasses With Glass-Transition Temperatures Below Room Temperature, Andrei Jitianu, Guadalupe Gonzalez, Lisa C. Klein

Publications and Research

Melting gels are hybrid gels that have the ability to soften and flow at around 100 ° C for some combinations of mono- and di-substituted alkoxysiloxanes, where substitutions are either all aromatic or all aliphatic. In this study, melting gels were prepared using phenyltriethoxysilane (PhTES) and dimethyldiethoxysilane (DMDES), meaning both an aromatic and aliphatic substitution. Differential scanning calorimetry was performed to identify glass-transition temperatures, and thermal gravimetric analysis coupled with differential thermal analysis (TGA-DTA) was performed to measure weight loss. The glass-transition temperatures ( T g ) ranged from – 61 ° C to + 5.6 ° C, which are …

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …

Two Distinct Modes Of Metal Ion Binding In The Nuclease Active Site Of A Viral Dna-Packaging Terminase: Insight Into The Two-Metal-Ion Catalytic Mechanism, Haiyan Zhao, Zihan Lin, Anna Y. Lynn, Brittany Varnado, John A. Beutler, Ryan P. Murelli, Stuart F.J. Le Grice, Liang Tang

Publications and Research

Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg2+. A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 A° . Such proximity of the two metal ions may play an essential role in catalysis by …

Zirconium-89: Radiochemistry And Ligand Development Toward Improved Pet Applications, Melissa Ann Deri

Dissertations, Theses, and Capstone Projects

Antibodies are attractive targeting vectors for positron emission tomography (PET) based imaging agents due to their high affinity and selectivity to a variety of biological targets. Creating such imaging agents requires a radionuclide with suitable decay characteristics. This role has been filled by zirconium-89 which has a 78.41 h half-life that ideally matches the multi-day biological half-life of IgG antibodies.

However, the use of a radiometal necessitates the use of a bifunctional chelator to bind the metal and conjugate to the antibody. For ⁸⁹Zr this has been the purview of various derivatives of desferrioxamine B (DFO); however, the observed …

Accessing Medicinally-Relevant Scaffolds Via Organocatalyzed Cascade Reactions, Joshua Hadley Jones

Dissertations, Theses, and Capstone Projects

The field of asymmetric catalysis embodies the efforts of chemists to mimic the stereoselectivity routinely achieved by biological systems. Asymmetric organocatalysis, a sub-field of asymmetric catalysis, is broadly based on the catalytic activity of non-transition metal, small molecules that transmit chirality to substrates. This dissertation describes experimental work towards the construction of versatile, medicinally-relevant molecular scaffolds using chiral, diarylprolinol silyl ether organocatalysts. Specifically, these catalysts were used in 1-pot, iminium-enamine catalyzed cascade reactions to functionalize α,β-unsaturated aldehydes. A comprehensive review of iminium and enamine organocatalysis is provided, including its development towards iminium-enamine cascade reactions. This review provides background for the …

Density Functional Theory For The Investigation Of Transition Metal Complexes: Structure, Binding, And Spectroscopy Of Metal-Siderophores And The Catalase-Peroxidase Enzyme, Bonnie I. Kruft

Dissertations, Theses, and Capstone Projects

Since the development of quantum mechanics in the 1920's and with the introduction of the Schrödinger equation in 1926, various methods to solve the Schrödinger equation have evolved. With advances in these computational methods, we are now able to solve the Schrödinger equation for systems that did not seem possible less than a century ago. Density functional theory (DFT) is a valuable tool for the exploration of the molecular properties of biological systems, and is based upon the theory that the exact energy could be determined from the knowledge of the electron density. The purpose of this dissertation is to …

Large-Pore Mesoporous Organosilicas And Related Polymer Nanocomposites, Amanpreet Singh Manchanda

Dissertations, Theses, and Capstone Projects

The research work in this dissertation covers the synthesis of mesoporous organosilicas and (organo)silica/polymer nanocomposites. The content can be divided into 4 parts (8 chapters).

The first part of the dissertation is the introduction, which covers the background and progress in the field of mesoporous silicas, periodic mesoporous organosilicas and related inorganic/polymer nanocomposites. The second part of the dissertation (Chapter 2-5) involves the synthesis of mesoporous organosilicas from different organosilane precursors at mild acid concentration (0.1 M HCl) and low temperature (0 or 7 ℃) using Pluronic F127 (EO₁₀₆PO₇₀EO₁₀₆) as a surfactant template. Chapter …

Polymer Pen Printing: A Tool For Studying 2d Enzymatic Lithography And Printing 3d Carbon Features, Zhantong Mao

Dissertations, Theses, and Capstone Projects

Polymer Pen Lithography (PPL) is a promising molecular printing approach which combines the advantages of both microcontact printing (low cost, high-throughput) and the dip pen lithography (DPN) (arbitrary writing, high-resolution) into one cohesive lithography method to create 2 dimensional (2-D) patterns with micro/nano-features on different substrates. The goal of this dissertation is to design and develop a new tool based upon PPL, which is not limited to forming 2D parallel patterns, but can also create 3D complex microstructures, finding applications in both biotechnology and Micro-Electro-Mechanical systems (MEMS) technology. This novel approach is named Polymer Pen Printing. Different from PPL using …

Studies Toward A General Synthesis Of Poly-Substituted Alpha-Hydroxytropolones, Christine Marie Meck

Dissertations, Theses, and Capstone Projects

Chapter 1: This chapter gives a brief history of α-hydroxytropolones, how they were discovered and unique properties of these substrates. Included is a background on the bioactivity of these substrates in cellular targets such as bacteria, fungi, parasites, tumors and toxicity, as well as their ability to inhibit various metallo-based enzymes. Structure activity relationships studies are reviewed on important metalloenzymes HIV-Reverse Transcriptase (RT) and Inositol monophosphatase (IMPase). Finally the chapter finishes with a synthetic overview of α-hydroxytropolones including natural product targets such as puberulic acid, puberulonic acid, β-thujaplicinol, and β-hydroxytropolone.

Chapter 2: A brief review on β-hydroxy-γ-pyrone based oxidopyrylium cycloadditions …

Molecular Helices As Electron Acceptors In High-Performance Bulk Heterojunction Solar Cells, Yu Zhong, M. Tuan Trinh, Rongsheng Chen, Geoffrey E. Purdum, Petr P. Khlyabich, Melda Sezen, Seokjoon Oh, Haiming Zhu, Brandon Fowler, Boyuan Zhang, Wei Wang, Chang-Yong Nam, Matthew Y. Sfeir, Charles T. Black, Michael L. Steigerwald, Yueh-Lin Loo, Fay Ng, X.-Y. Zhu, Colin Nuckolls

Publications and Research

Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non-fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealed …

A Mechanism For Biologically Induced Iodine Emissions From Sea Ice, A. Saiz-Lopez, Christopher S. Blaszczak-Boxe, L. J. Carpenter

Publications and Research

Ground- and satellite-based measurements have reported high concentrations of iodine monoxide (IO) in coastal Antarctica. The sources of such a large iodine burden in the coastal Antarctic atmosphere remain unknown.We propose a mechanism for iodine release from sea ice based on the premise that micro-algae are the primary source of iodine emissions in this environment. The emissions are triggered by the biological production of iodide (I�) and hypoiodous acid (HOI) from micro-algae (contained within and underneath sea ice) and their diffusion through sea-ice brine channels, ultimately accumulating in a thin brine layer (BL) on the surface of sea ice. Prior …

Comparative Sorption Of Methylene Blue Onto Hydrophobic Clays, Alvaro D. Sponza, Natalia J. Fernandez, David Yang, Karla A. Ortiz, Abel E. Navarro

Publications and Research

Chemical modifications of clay to remove methylene blue (MB) from aqueous solutions at room temperature were compared. Natural bentonite (NC) was modified by cation exchange with hexadecyltrimethylammonium chloride (HC), bencyltriethylammonium chloride (BC), and tetramethylammonium chloride (TC) to reverse the surface polarity of the hydrophilic bentonite. The adsorption of MB was studied and fitted by the adsorption theories of Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin. Equilibrium parameters were calculated, indicating that chemical modification did not improve the adsorption, due to the electrostatic adsorption mechanism. Specific surface area was determined, reporting the following trend: NC > TC > BC > HC. Isotherms show that TC is …

Polycations Xxii. Ru(Bpy)2l2 And Ru(Phen)2l2 Systems With Cationic 4,4’-Bipyridine Ligands: Syntheses, Characteristics, And Interactions With Dna, Jasmine Hatcher, Freida Zavurov, Leslie Babukutty, Thomas Strekas, Robert Engel

Publications and Research

Earlier efforts have been concerned with the association of Ruthenium octahedral complexes with DNA. Since the positively charged ruthenium species has been found to associate with the electron rich major groove of double-stranded DNA, it was proposed the addition of cationic sites on the ligands attached to ruthenium would facilitate such association. Thus, we have synthesized several series of octahedral ruthenium complexes bearing ligands having within themselves cationic sites. These have been investigated in their interaction with calf thymus DNA using fluorescence titration analysis. The introduction of the cationic ligands has been found to exhibit enhanced association of the ruthenium …