493 research outputs found
An Exploration of Therapeutic Applications for Dinitrosyl Iron Complexes (DNIC's)
No full textThe therapeutic nature and mechanisms of in vitro nitric oxide (NO) release from dinitrosyl iron complexes (DNICs) are explored herein. First, the ideal primary coordination environment for the sustained liberation of NO while limiting the toxicity related to iron and NO was investigated. Dimeric RRE-type {Fe(NO)2}9 complexes, SPhRRE [(��-SPh)Fe(NO)2]2 and TGTA-RRE, [(��-S-TGTA)Fe(NO)2]2 (TGTA = 1-thio-��-d-glucose tetraacetate), were found to deliver NO with the lowest effect on cell toxicity (i.e., highest IC50) with TGTA-RRE delivering a higher concentration of NO to the cytosol of SMCs. Monomeric DNICs with bulky N-heterocyclic carbenes (NHC), namely 1,3-bis(2,4,6-trimethylphenyl)imidazolidene (IMes), have IC50���s of ~7 ��M, but didn���t release NO into SMCs. The reduced, mononuclear {Fe(NO)2}10 neocuproine-based DNIC increased intracellular NO.
Given the efficacy of TGTA-RRE, instead of redesigning entirely new DNICs, the release rate of NO was tuned with the addition of biomolecules histidine and glutathione. From the Griess assay and X-band EPR data, decomposition of the histidine-cleaved dimer, [(TGTA)(NHis)Fe(NO)2], generated Fe(III) and increased the NO release rate compared to the TGTA-RRE precursor. In contrast, increasing concentrations of glutathione generated the stable [(TGTA)(GS)Fe(NO)2]- and depressed the NO release rate. This work provides insight into tuning NO release beyond the design of DNICs, through the incubation with biomolecules.
A structure activity relationship between thiolate identity and expected protease inhibition was investigated in silico and in vitro via AutoDock 4.2.6 (AD4) and FRET protease assays respectively. AD4 was validated for coordinatively unsaturated DNIC binding using a crystal structure of a protein-bound DNIC, PDB ��� 1ZGN (calculation RMSD = 1.77). The dimeric DNICs TGTA-RRE and TG-RRE, [(��-S-TG)Fe(NO)2]2 (TG = 1-thio-��-d-glucose), were identified as leads via the in silico study. Computations suggest inhibition at the catalytic Cys145 of SC2Mpro. In vitro studies indicate inhibition of protease activity upon TGTA-RRE treatment, with an IC50 of 38 ��M for TGTA-RRE and 33 ��M for TG-RRE. This study presents a simple computational method for predicting DNIC-protein interactions as well as validating the in silico leads in vitro
Macrocyclic Dibridgehead Diphosphines That Turn Themselves Inside Out and Their Platinum Adducts: A Tour Through Three Oxidation States
No full textThe broad field of molecular rotors is highly relevant to several types of molecular machines and chemists have had an ongoing interest in the sub-nanoscale miniaturization of various macroscopic devices. Two classes of metal complexes with the general formula cis/transPt(Cl)2 (P((CH2 )n )3P) have been intensively studied by Gladysz et al., which are often termed ���gyroscope like��� (trans) or ���parachute like��� (cis) due to their structural similarity to their corresponding macroscopic counterparts. Research on the reactivities and structures is of potential interest, as structure alterations can optimize the dynamic behaviors of such molecules, thereby influencing their performance as molecular rotors. Thus, a comprehensive study of the syntheses, structures, and reactivities of various platinum complexes and related phosphine ligands is detailed in this dissertation.
The research on the substitution chemistry of the square planer gyroscope like dichloride complexes trans-Pt(Cl)2 (P((CH2 )n )3P) is first elaborated in chapter 2. Normally, isomerization to the cis configuration occurs upon reactions with alkyl lithium reagents to give the dialkyl complexes cis-Pt(R)2 (P((CH2 )n )3P) (R = Me, Et). These subsequently react with HCl to generate trans-Pt(Cl)(R)(P((CH2 )n )3P). In the case of R = Me, cis-Pt(Cl)(Me)(P((CH2 )n )3P) is isolated, which easily converts to its trans isomer over silica gel or at elevated temperature. A series of thermolyses experiments and DFT calculations indicate that the trans/gyroscope complexes have lower energies than cis/parachute complexes, except for dialkyl complexes which have comparable energies.
Chapter 3 turns attention to a closely related field of macrocyclic dibridgehead diphosphines P((CH2 )n )3P), which are prepared by demetalation of cis/trans-Pt(Cl)2 ((P((CH2 )n )3P) with a nucleophile MC���X, in certain cases in decent yields. These ligand frameworks demonstrated high flexibility with extensive conformational manifolds and coordination modes. Apparent configurational isomerizations between in,in/out,out and in,out/out,in species are showcased, and the homeomorphic isomerizations within each manifold are further characterized by variable temperature NMR data.
Studies on octahedral platinum(IV) complexes are described in chapter 4. The gyroscope like platinum(IV) tetrahalide complexes trans-Pt(X)4 (P((CH2 )n )3P) (X = Cl, Br) are obtained by treating the square planar platinum(II) dihalide complexes trans-Pt(X)2 (P((CH2 )n )3P) with excess X2 . Their crystal structures are compared to those of Pt(II) precursors. In one exploratory attempt, trans-Pt(Me)4 (P((CH2 )n )3P) was isolated in a reaction of trans-Pt(Br)2 (P((CH2 )n )3P) with MeMgBr, as verified crystallographically. The cis parachute isomer was obtained by treatment of the free dibridgehead diphosphine P((CH2 )14)3P with the PtMe4 source Pt2Me8 (��-SMe2 )2 .
Chapter 5 of this dissertation deals with an ongoing pursuit of the platinum(0) complex trans-Pt(P((CH2 )14)3P), which has been generated by the reaction of trans-Pt(Cl)2 (P((CH2 )14)3P) and C8K in C6D6 or diethyl ether. The NMR data (31P{1H} chemical shift and JPPt) closely resembles similar trans-Pt(PR3 )2 species in the literature. Treatments of this transient species with MeI and H2 afford the corresponding platinum(II) oxidative addition products, as evidenced by 31P{1H} and 1H NMR. Moreover, additions of ethylene and diphenylacetylene give 1:1 �� adducts, believed to have trigonal geometries based upon similar literature compounds
Complexes Containing a Direct, Unsupported Lanthanide-Transition Metal Bond
No full textThe synthesis and characterization of molecules containing a direct, unsupported lanthanide transition metal bond is an ambitious task. Adding to this challenge, it is difficult to design a system in which both the lanthanide and transition metal can be interchanged to assess the nature of this interaction. As metal-metal bonding has provided significant insights into chemical bonding, catalysis, and electronic structure, it is important to pursue this rarely reported interaction. Additionally, lanthanide-transition metal heterometallics have drawn recent interest in the field of single-molecule magnetism (SMMs).
Initially, dinuclear lanthanide complexes containing bridging chloride (Cl��) or triflate (OCF3SO2 - ) ligands were isolated as synthons for future reactions. These complexes were successfully prepared by reacting a dysprosium salt with the previously reported 2,6- bis(methylenecyclopentadienyl)pyridine disodium salt Nav2PyCp2 (PyCpv2 = 2,6- (CHv2Cv5H3)2C5Hv3N]^2- ) to yield [(PyCpv2)Dy(��-OTf)]v2 and [(PyCp2)Dy(��-Cl)]2. Of note, this was the first structurally characterized organometallic dysprosium triflate complex. These complexes exhibited properties of an SMM as evidenced by static and dynamic magnetic measurements. Despite the identity of the bridging ligand differing in the compounds, both exhibited a similar energy barrier (U) to reorient spin.
As dysprosium garners substantial attention in the field of SMMs, complexes containing a Dy-TM were first targeted. The reaction between [(PyCpv2)Dy(��-OTf)]v2 and anionic transition metal fragments KFp or KRp (Fp = [CpFe(CO)v2] - , Rp = [CpRu(CO)v2]), afforded the complexes PyCpv2Dy-FeCp(CO)v2 and PyCp2Dy-RuCp(CO)v2. Infrared and M��ssbauer spectroscopic studies suggested this interaction to be strong TM���Dy bonding interactions which is further supported by computational analysis.
Magnetization dynamics performed in this study determined both compounds exhibited field induced slow magnetic relaxation with similar barriers despite different relaxation times. A later study compared the spectroscopic and magnetic properties of (thf)PyCpv2Ce-FeCp(CO)v2 to that of PyCpv2Dy-FeCp(CO)2 and concluded that the identity of the lanthanide has an influence on the magnetic properties of these heterobimetallic systems. Spectroscopic and computational analysis demonstrated weaker TM���Ln interactions in the (thf)PyCp2CeFeCp(CO)2 as compared to PyCp2Dy-FeCp(CO)v2. Preliminary findings on other Ln-TM bonded complexes isolated with this ligand system will be shared
Theoretical Aspects of Werner Complexes and Molecular Devices
No full textThis dissertation begins with the first comprehensive review of molecular gyroscopes. The following two chapters feature combined experimental/computational studies. In the first, equilibria involving gyroscope-like complexes and geometric isomers are measured and the data interpreted with molecular dynamics simulations and DFT calculations. In the second, trigonal bipyramidal diiron tetraphosphorus complexes that have parallel P���Fe���P axes and the potential for coupled Fe(CO)3 rotators are examined. Here the DFT studies focus mainly on electronic structure and IR properties.
The rotators can be removed from the gyroscope-like complexes to give unprecedented dibridgehead diphosphines with long (CH2)n linkers. Their conformational, dynamic, and NMR properties are interrogated by simulated annealing and DFT calculations, helping to rationalize observed behavior and predicting properties of molecules that remain to be synthesized.
Another major class of molecules investigated is polyynes H(C���C)n'H which are of special interest at long chain lengths (models for the polymeric sp carbon allotrope carbyne). Nucleus independent chemical shifts are revealing an absence of special shielding regions and DFT calculations provide highly accurate chemical shift values, including polyynes with platinum endgroups. Complexes with four platinum corners and four ���(C���C)2��� edges can be accessed. Electrostatic potential maps show highly negatively charged cores that explain the strong affinities of these species for ammonium salts. DFT calculations also establish very similar energies for planar vs. puckered conformations, both of which have been observed crystallographically: electronic structures and equilibria involving Pt3 and Pt5 homologs are also thoroughly explored.
Werner complexes of the type [Co(en)3]3+ 3X��� (en = 1,2-ethylenediamine) have also been extensively investigated. In one study, the intricate stereochemical and conformation properties are reviewed including substituted derivatives using conventions from both organic and inorganic chemistry. In another, >150 crystal structures of [Co(en)3]3+ salts have been analyzed with respect to hydrogen bonding between the NH groups and the counteranions. Diverse motifs could be identified and a nomenclature syntax developed
Structures and Applications of Porous Coordination Cages
No full textWell defined porous coordination cages (PCCs) are cage-like compounds constructed from the self-assembling of organic ligands and metal ions through coordination interactions. These metalorganic materials can exist in solution as standalone cage-like host systems that can be structurally tuned towards specific purpose. The unique environment that PCCs create in solution allows for interesting guest-binding behaviors inside the cavity, which has been exploited as catalytic sites, gas binding and storage and drug binding for cellular delivery. This dissertation work seeks to gain more understanding into the PCC as a host system in the context of structural dynamics in solution and host-guest interactions, which can provide important insights into the application implications in catalysis and drug delivery. In Chapter 2, using PCC-20 as a model PCC system, I aimed to understand how the PCC host systems exist and maintain structural integrity in solution. The structural manipulation and control over the shape and size of PCC-20 were found to be achievable by external stimuli, such as, heat, light, guest molecules and solvent environments. In Chapter 3 and 4, using PCC-2 as a host system, I sought to understand how the electrostatic interactions of PCCs with their guests, including rhodamine B and metal nanoclusters, can induce changes in the guest structures and shape the guest towards certain direction. These host-guest interactions can be exploited to catalytic applications. In Chapter 5, PCC-1, as a model PCC for drug delivery, was assessed for biocompatibility
Developing Commercially Scalable Iron and Titanium Metal-Organic Frameworks for Gas Storage and Water Purification
No full textSince their discovery in the late 1990s, Metal-Organic Frameworks (MOFs) have turned into one of the fastest growing classes of materials studied in the chemical literature. MOFs have shown promise in applications such as gas storage, chemical separations, chemical sensing, catalysis, and even drug delivery. Their wide range of potential applications can be attributed to their ultra-high surface area, high crystallinity and tunable physical and chemical properties. However, the potential applications of MOFs have been slow to develop into viable and sustainable products at the commercial or industrial level.
Chapter I of this dissertation discusses the background of Metal-Organic Frameworks (MOFs), the current limitations of MOFs that prevent wide spread commercial production such as stability, processing cost, and synthesis cost as well as how the research performed aimed to address these challenges.
In Chapter II details a method that was developed in order to synthesize a Hierarchally Porous (HP) variant of a commercially available MOF named PCN-250(Fe3O). The method developed utilizes the addition of fatty acids during MOF synthesis in order to induce and engineer hierarchal porosity within PCN-250(Fe3O). The resulting Hierarchally Porous MOFs (HP-MOF) exhibited completely different mesoporosity in size, volume, and position. Furthermore, the PCN-250(C9-1.4M) material obtained adsorbs/removes 100% of Methylene Blue, a common organic dye, from aqueous solution, as compared to the microporous variant of PCN-250(Fe3O), which only removes 31%
Chapter III builds on the use of PCN-250(Fe3O) as a material for removing organic dyes from water, but utilizes PCN-250(Fe3O) as a catalyst, not just an adsorbent. PCN-250 was reported to be a successful and recyclable Fenton and photo-Fenton catalyst that degrades 100% of Methylene Blue. Overall, 4 different variants of PCN-250 were synthesized and named PCN-250(Fe3O), PCN-250(Fe2Ni), PCN-250(Fe2Co) and PCN-250(Fe2Mn). The catalytic degradation efficiency for both Fenton and photo-Fenton reactions was improved by the isomorphic substitution of Mn and Co for Fe, but inhibited by the incorporation of Ni.
Chapter IV details the development of a photo-catalytic system for the degradation of Per/Poly-Fluorinated Alkyl Substances (PFASs) using a commercially scalable Ti-Based MOF. With the developed photo-catalytic system, the concentration of Perfluorooctanoic acid (PFOA) can be reduced by 49% and with a 21.1% fluoride mineralization efficiency in 24 hours. Overall, this work has shown the ability to successfully design Metal-Organic Frameworks based photo-catalytic platforms for chemically reducing (degrading) Per- and polyfluoroalkyl substances (PFAS) in water and is to the best of our knowledge the first successful example of using MOFs for PFAS degradation.
Chapter V, details the development of a novel MOF processing method that maximizes the surface area while minimizing cost. The method is a suspension-based processing 3 step method that maximizes the porosity of MOFs by more effectively solubilizing unreacted starting materials and more importantly, removing area of low crystallinity from the surface of MOF particles. In the last chapter, Chapter VI, a summary of the current work is given along with my thoughts and outlooks on future of MOFs
Measurements of the inclusive semileptonic branching ratio and average lifetime of b-hadrons at LEP and the determination of
No full textThe Kinetics of the Dehydrogenative Borylation of Terminal Alkynes and Exploration of the Reactivity of PXP Ligated Cobalt Complexes
No full textCatalytic synthesis of borylated organic molecules has been of great interest given the synthetic utility of borylated material in cross-coupling reactions. However, a glaring absence from the synthetic chemist���s repertoire was the catalytic synthesis of borylated alkynes. In 2013, the Ozerov group disclosed pincer iridium complexes capable of performing the dehydrogenative borylation of terminal alkynes (DHBTA). In the following years, second generation catalysts were disclosed using the 2,2���-bis(dialkylphosphino)diphenylamide (PNP) ligand.
Here we continue the development of PNP ligated iridium DHBTA catalysts and disclose a full mechanistic investigation coupling experimental results with computational investigation. Also disclosed is the first example of a readily available, air-stable iridium DHBTA precatalyst. We have discovered that the DHBTA reaction is moderately tolerant to air and moisture with sufficient pinacolborane present. The ease of handling this new precatalyst will hopefully inspire widespread use of catalytic methods for the construction of alkynylboronates.
Inspired by our success with (POCOP)Rh(Ar)(SAr���) and (PNP)Rh(Ar)(SAr���) in C���S bond formation reactions, (POCOP)Co(Ar)(SAr���) and (PNP)Co(Ar)(SAr���) were synthesized and their efficacy in C���S bond formation was investigated. The (POCOP)Co and (PNP)Co platforms were determined to be incapable of supporting catalysis. The former was prone to reductive elimination involving the pincer aryl and the latter was plagued by a swift comproportionation reaction after concerted two electron C���S reductive elimination. The mechanism of thiolate scrambling and C���S coupling in the (PNP)Co system was investigated in detail. A series of aryl halides were added to the (PNP)Co system to capture cobalt after reductive elimination hopefully eliciting oxidative addition to the unsaturated (PNP)Co fragment; however, halogen atom abstraction predominated. The halogen atom abstraction and scrambling of ligands between cobalt centers was investigated.
Esterified phenols are attractive substrates for Suzuki-style coupling reactions given the ubiquity of phenols and the stability of the corresponding ester. To this end, the (PNP)Co system was applied to the C���O cleavage of esters. Although the active CoI/III comproportionation reaction prevents catalysis, this is the first documented example of cobalt mediated aryl ester C���O bond activation.
Lastly, the synthesis, characterization, and structural characterization of various cobalt silylene complexes are disclosed
Structures and Applications of Porous Coordination Cages
No full textWell defined porous coordination cages (PCCs) are cage-like compounds constructed from the self-assembling of organic ligands and metal ions through coordination interactions. These metalorganic materials can exist in solution as standalone cage-like host systems that can be structurally tuned towards specific purpose. The unique environment that PCCs create in solution allows for interesting guest-binding behaviors inside the cavity, which has been exploited as catalytic sites, gas binding and storage and drug binding for cellular delivery. This dissertation work seeks to gain more understanding into the PCC as a host system in the context of structural dynamics in solution and host-guest interactions, which can provide important insights into the application implications in catalysis and drug delivery. In Chapter 2, using PCC-20 as a model PCC system, I aimed to understand how the PCC host systems exist and maintain structural integrity in solution. The structural manipulation and control over the shape and size of PCC-20 were found to be achievable by external stimuli, such as, heat, light, guest molecules and solvent environments. In Chapter 3 and 4, using PCC-2 as a host system, I sought to understand how the electrostatic interactions of PCCs with their guests, including rhodamine B and metal nanoclusters, can induce changes in the guest structures and shape the guest towards certain direction. These host-guest interactions can be exploited to catalytic applications. In Chapter 5, PCC-1, as a model PCC for drug delivery, was assessed for biocompatibility
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