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- Title
- TUMOR-ASSOCIATED MUC1-TN GLYCOPEPTIDE INTERACTIONS WITH MACROPHAGE GALACTOSE LECTIN.
- Creator
- Beckwith, Donella Marie, Cudic, Mare, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Mucin 1 (MUC1), the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern in many cancers. The presence of truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play key roles in tumor initiations, progression, and metastasis. Accumulating evidence...
Show moreThe transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Mucin 1 (MUC1), the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern in many cancers. The presence of truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play key roles in tumor initiations, progression, and metastasis. Accumulating evidence suggests that expression of TACAs is associated with escape of immune defenses. Human macrophage galactose-type lectin (hMGL, HML, CD301 or CLEC10A), a C-type lectin expressed by antigen presenting cells (APC), is a receptor of mucin-type TACAs, -GalNAc (Thomsen nouvelle antigen; Tn; CD175) and its 2,6-sialylated derivative (sTn; CD175s). To date, the relative contributions of these glycans, as well as underlying peptide backbone, and different degrees of valency, on binding thermodynamics and kinetics with hMGL remains elusive. In order to discern the subtle utility of these distinct features, chemical syntheses of the MUC1, HGVTSAPDTRPAPGSTAPPA tandem repeat sequence, and its site-specific serine (Ser) and threonine (Thr) glycosylated analogs were carried out. Circular dichroism (CD) spectroscopy experiments detected increasing structural order of the Thr glycopeptides compared to its nonglycosylated analogs. Isothermal titration calorimetry (ITC) data analysis of lectin binding to the Thr glycopeptides invariably showed enthalpy-driven processes. Affinity enhancement of the Thr glycopeptides for hMGL occurred relative to free GalNAc, revealing an increasing trend in affinity by one order of magnitude, for mono- (KD = 6-8 μM) to triglycosylated (KD = 600 nM) MUC1 peptides. To delineate the relevance of the solvent structure in the protein carbohydrate recognition process, experiments in D2O were performed, exposing enthalpy-entropy compensation differences. KinITC analysis highlighted prolonged complex lifetimes. Furthermore, atomic force microscopy (AFM) based dynamic single-molecule force spectroscopy (SMFS) provided molecular level insight into the energy landscapes governing recognition of the MUC1(Tn)-hMGL complexes. In summary, our results suggest that contact with hMGL critically depends on the type of TACA, nature of the vicinity surrounding the glycan, and its density. This highlights the importance and current efforts in design of prophylactic and therapeutic cancer vaccines with special emphasis on the synthetic glycopeptide vaccines.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013750
- Subject Headings
- Antigens, Tumor-Associated, Carbohydrate, Mucin-1, Cancer vaccines, Glycopeptides
- Format
- Document (PDF)
- Title
- Toward the synthesis of organic moieties for use in luminescent lanthanide materials: from benzodithiophene based linkers to a series of 2,3 pyridinedicarboxylate coordination polymers.
- Creator
- Ramirez, Amanda Lyn Staggers., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The main focus of this thesis is to present the structural and photophysical characteristics of the coordination polymers [Ln(C7H3NO4)(C7H4NO4)(H2O)]n (Ln is Pr, Nd, Sm, Eu, and Tb), as well as attempting to synthesize the novel organic linker 4,4'(4,8-Dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-diyl)dibenzoic acid (BDTDC). Various lanthanide salts were coordinated with 2,3-pyridinecarboxylate (2,3- pydc) via hydrothermal synthesis. ... Progress was made toward the synthesis of a novel metal...
Show moreThe main focus of this thesis is to present the structural and photophysical characteristics of the coordination polymers [Ln(C7H3NO4)(C7H4NO4)(H2O)]n (Ln is Pr, Nd, Sm, Eu, and Tb), as well as attempting to synthesize the novel organic linker 4,4'(4,8-Dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-diyl)dibenzoic acid (BDTDC). Various lanthanide salts were coordinated with 2,3-pyridinecarboxylate (2,3- pydc) via hydrothermal synthesis. ... Progress was made toward the synthesis of a novel metal-organic framework linker BDTDC. Synthesis of the intermediate benzo[1,2-b:4,5-b']dithiophene as well as the determination of the crystal structure, were performed successfully and are reported herein.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362561
- Subject Headings
- Metathesis (Chemistry), Supramolecular chemistry, Organic compounds, Synthesis, Macromolecules, Synthesis
- Format
- Document (PDF)
- Title
- Toward lanthanide containing coordination polymers and nanomaterials.
- Creator
- Greig, Natalie E., De Lill, Daniel T., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The focus of this thesis is to develop lanthanide (Ln) luminescent materials through the exploration of coordination polymers and nanomaterials. Herein, dimethyl-3,4- furanedicarboxylate acid undergoes hydrolysis under hydrothermal conditions to form coordination polymers with lanthanide ions. The resulting coordination polymers exhibited luminescent properties, with quantum yields and lifetimes for the Eu-and Tb-CP of 1.14+-0.32% and 0.387=-0.0001 mx, and 3.33=-0.82% and 0.769=-0.006 ms,...
Show moreThe focus of this thesis is to develop lanthanide (Ln) luminescent materials through the exploration of coordination polymers and nanomaterials. Herein, dimethyl-3,4- furanedicarboxylate acid undergoes hydrolysis under hydrothermal conditions to form coordination polymers with lanthanide ions. The resulting coordination polymers exhibited luminescent properties, with quantum yields and lifetimes for the Eu-and Tb-CP of 1.14+-0.32% and 0.387=-0.0001 mx, and 3.33=-0.82% and 0.769=-0.006 ms, respectively. While the incorporation of lanthanides was not achieved in this work, progress toward the production of pure phase InP in the nanoregime has been made, using a low-cost, hydrothermal method. Through SEM and PXRD conflict, it is believed that pure INP particles with a size range of 58-81 nm were successfully synthesized.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358558
- Subject Headings
- Metallic composites, Speciation, Lanthanide shift reagents, Rare earth metals catalysts, Nanostructured materials
- Format
- Document (PDF)
- Title
- Therapeutic potential, mechanism of action, and ecology of novel marine natural products.
- Creator
- Winder, Priscilla L., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the...
Show moreThe projects described in this dissertation are focused on compounds derived from the marine environment. Chapter 1 gives an introduction to the study of marine natural products to treat human ailments and a thorough review on compounds from lithistid sponges that have been isolated or synthesized since 2000. Chapter 2 describes the isolation and structure elucidation of two sesquiterpene substituted benzoquinone derivatives, petrosiquinones A and B, from a deep-water marine sponge from the Family Petrosiidae. Although initially purified following activity in a (Sb(B-catenin/Tcf4 assay they were later followed using tumor cell line cytotoxicity assays. Petrosiquinone A was the more active of the two compounds with moderate cytotoxicity in the DLD-1, PANC-1, and AsPC-1 cell lines. In Chapter 3, the isolation and structure elucidation of two new marine-derived macrolides, madeirolide A and B, isolated from a deep-water lithistid sponge of the genus Leiodermatium is described., They were isolated using numerous chromatographic techniques and the structures were elucidated on the basis of 1D and 2D NMR spectra coupled with high resolution-mass spectrometry (HR-MS) data. Madeirolide A and B inhibited the growth of the fungal pathogen Candida albicans with minimum inhibitory concentrations (MIC) of 12.5 and 25 (So(Bg/mL, respectively, but were not cytotoxic in tumor cell assays under the conditions tested. Chapter 4 describes work performed to determine the molecular target of lasonolide A using affinity chromatography. The target of lasonolide A is of interest since lasonolide A is known to kill cancer cells in vitro through a unique mechanism., This chapter highlights the research performed to create an affinity matrix with immobilized lasonolide. A target has not been confirmed but there are a number of interesting hits that are being pursued. In Chapter 5, a liquid chromatography-mass spectrometry (LC-MS) screening method was established in order to rapidly identify the metabolites from numerous collections of Lyngbya spp. obtained from Broward and Lee County, Florida sites that may help marine ecologists assess the effects of Lyngbya spp. blooms on the environment. A link between the metabolites produced and nutrients from both the algal tissue and water column was also explored.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/369392
- Subject Headings
- Natural products, Therapeutic use, Sponges, Ecology, Marine resources, Research, Marine biotechnology
- Format
- Document (PDF)
- Title
- THE ROLE OF MATRIX METALLOPROTEINASE-28 IN HEALTH AND DISEASE.
- Creator
- Tokmina-Roszyk, Dorota, Fields, Gregg B., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Matrix Metalloproteinase-28 (MMP-28) is the newest and least characterized member of MMP family. To date several potential substrate candidates for MMP-28 have been proposed but no in vivo substrates for this enzyme were confirmed. In the central nervous system (CNS) MMP-28 is believed to be important factor during myelination of the developing nervous system as well as during remyelination that follows neuronal injury. On the other hand, MMP-28 has been found in actively demyelinating...
Show moreMatrix Metalloproteinase-28 (MMP-28) is the newest and least characterized member of MMP family. To date several potential substrate candidates for MMP-28 have been proposed but no in vivo substrates for this enzyme were confirmed. In the central nervous system (CNS) MMP-28 is believed to be important factor during myelination of the developing nervous system as well as during remyelination that follows neuronal injury. On the other hand, MMP-28 has been found in actively demyelinating lesions in both experimental autoimmune encephalopathy (EAE) and multiple sclerosis patients suggesting its possible role in pathological events associated with autoimmune neurodegenerative processes. In addition, MMP-28 has been linked to modulation of immune response and activation of macrophages which presents another role of this enzyme in autoimmune pathologies. In the study described herein, MMP-28 has been shown to affect myelin composition and appearance, mitochondrial protein content, and vesicular transport proteins. Moreover, the decrease in myelin basic protein quantity observed in healthy MMP-28KO animals affected the myelin staining intensity in various brain regions including corpus callous. Cellular energetic studies did not reveal differences in mitochondrial function in MMP-28KO animals and no difference in reactive oxygen species was observed. In the EAE model, MMP-28 deletion increased the occurrence of atypical form of EAE characterized by increased inflammation of arbor vitae of the brain. In addition, MMP-28 deletion decreased the inflammatory infiltrates present in brains obtained from EAE animals. Lastly, MMP-28 has been shown to affect cellular energetics and activation of bone marrow derived macrophages during the initial stages and after 24 h activation. In addition, MMP-28 deletion increased proinflammatory cytokines and receptors CD86 and iNOS found in M1 polarized macrophages.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013601
- Subject Headings
- Matrix Metalloproteinases, Multiple sclerosis, Neurodegenerative disease
- Format
- Document (PDF)
- Title
- Targeted Drug Delivery Utilizing a Mini-Collagen Ligand Recognized by CD44/CSPG Melanoma Receptor.
- Creator
- Khan, David R., Florida Atlantic University, Fields, Gregg B., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Liposomes of varying lipid compositions are currently used as drug carriers. and great efforts have been made to target these vehicles to specific cellular receptors. Previous targeting components include peptides. proteins. antibodies. or vitamins. CD44/CSPG is among the receptors overexpressed in metastatic melanoma. and the sequence to which it binds within the type IV collagen triple-helix has been identified. A triple-helical '·peptide-amphiphile .. (al(JV)1263-1277 PA) which binds CD44...
Show moreLiposomes of varying lipid compositions are currently used as drug carriers. and great efforts have been made to target these vehicles to specific cellular receptors. Previous targeting components include peptides. proteins. antibodies. or vitamins. CD44/CSPG is among the receptors overexpressed in metastatic melanoma. and the sequence to which it binds within the type IV collagen triple-helix has been identified. A triple-helical '·peptide-amphiphile .. (al(JV)1263-1277 PA) which binds CD44/CSPG has been constructed and incorporated into liposomes of differing lipid compositions. Liposomes containing distearoyl phosphatidylcholine (DSPC) as the major bilayer component. in combination with distearoyl phosphatidylglycerol (DSPG) and cholesterol. were more stable than analogous liposomes containing dipalmitoyl phosphatidylcholine (DPPC) instead of DSPC. The presence of the al(JV)1263-1277 PA conferred greater stability to the DPPC liposomal systems. and did not affect the stability of the DSPC liposomes. The addition of either PEG 750 or PEG 2000 (5 mol %) to DSPG/DSPC/Chol liposomes did not affect the stability of this system. Fluorophore delivery of rhodamine loaded liposomes to cells varymg 111 CD44/CSPG expresston was determined usmg fluorescence microscopy. The CD44/CSPG receptor content for two normal fibroblast cell lines, BJ and Hs895Sk, and a highly metastatic melanoma derived cell line, M 14#5. was determined using whole cell ELISA. The results of the ELISA showed varying levels of CD44 receptors amongst the cell lines. with M 14#5 cells having the most. A positive correlation was observed for cellular fluorophore delivery by the ai(IV)1263-1277 PA liposomes and CD44/CSPG receptor content. Conversely, non-targeted liposomes delivered minimal fluorophore to cells regardless of the CD44/CSPG receptor content. When cells were treated with exogeneous a I (IV) 1263-1277, prior to incubation with a I (IV) 1263 -1277 PA liposomes, a dose-dependent decrease in the amount of fluorophore delivered was observed with respect to increasing concentrations of exogeneous al(IV)1263-1277. In addition, we have found a positive correlation between the cytotoxic effect of ai(IV)l263-1277 PA targeted liposomes (with and without PEG) loaded with doxorubicin and the CD44/CSPG content amongst the three different cell lines. This trend was not observed with non-targeted liposomes. These findings provide the possibility of a novel drug carrier system to be used in future clinical applications against metastatic melanoma.
Show less - Date Issued
- 2007
- PURL
- http://purl.flvc.org/fau/fd/FA00000866
- Subject Headings
- Tumor suppressor proteins, Antioncogenes, Drug targeting, Melanoma--Treatment
- Format
- Document (PDF)
- Title
- SYNTHETIC AND MECHANISTIC STUDY OF ENANTIO- AND STEREOSELECTIVE HOUSE–MEINWALD REARRANGEMENT OF CONGESTED TRISUBSTITUTED SPIRO-EPOXIDES.
- Creator
- Jeedimalla, Nagalakshmi, Roche, Stephane P., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Published Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357. The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro...
Show morePublished Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357. The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro-epoxides. Chapter 1 will present the efforts towards the biomimetic total synthesis of meroterpenoid natural product (+)-liphagal, which possess a recognizable biological activity. The shortcomings associated with its stereochemical assignment, and also the revision of stereochemical assignment of siphonodictyal B, through which the biosynthesis of (+)-liphagal was proposed were discussed. Chapter 2 will focus on the study of regio and chemoselective HMR reaction. In addition, a three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β, β’-disubstituted benzylidene cycloalkanes using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Second, an epoxidation followed by the HMR of spiro-epoxides is reported to produce a number of α -arylated cycloalkanones upon the ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), demonstrating the difficulty to achieve the ring enlargement for electron deficient spiro-epoxides. On the other hand, via catalysis with aluminium trichloride the rearrangement proceeded typically in high yields and with remarkable regioselectivity. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enabled this method to be successfully extended to some chemo specific arene shifts and it can also synthesize aldehydes derivatives bearing a α-quaternary carbon.
Show less - Date Issued
- 2019
- PURL
- http://purl.flvc.org/fau/fd/FA00013320
- Subject Headings
- Epoxy compounds, Epoxides, Biomimetic Materials--chemical synthesis
- Format
- Document (PDF)
- Title
- Synthesis, structural characterization and biological studies of organotin polyethers (Sn-O).
- Creator
- Barot, Girish Vallabhbhai., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin...
Show moreCancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture., These results support the starting premise that the polymers may exhibit cancer cell selectivity. In general, it was found that the presence of unsaturation increased the probability that the polyether would inhibit the growth of various cancer cell lines. Further, in some cases, polyethers with short distances between the oxygen atoms showed a superior ability to inhibit the growth of various cancer cell lines in comparison to those with longer distances between the oxygen atoms. These results provide a framework for the discovery of novel cancer therapeutics.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/186672
- Subject Headings
- Organometallic polymers, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Antineoplastic agents, Testing, Polymers in medicine
- Format
- Document (PDF)
- Title
- Synthesis of new materials containing metal-metal quadruple bonds: Complexes containing 2,2';6'2''-terpyridine, 4'-phenyl-2,2';6'2''-terpyridine, 2,3,5,6-tetrakis(alpha-pryidyl)pyrazine, and 1,3-bis(4-methylimino)isoindoline.
- Creator
- Hu, Chiwei, Florida Atlantic University, Baird, Donald M., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The presence of multiply bonded dimetal units in materials offers opportunities for tuning properties of solids. Materials containing molybdenum-molybdenum quadruple bonds have recently begun being reported. This thesis reports the products of the reactions of dimethyl sulfide (DMS), acetonitrile (ACN) and acetate complexes, Mo2CI4(DMS)4, Mo2(ACN)10ABF4, and Mo2(0Ac)4 with 2,2';6,2"-terpyridine, 4'-phenyl 2,2';6,2"-terpyridine, 2,3,5,6-tetrakis (alpha-pyridyl) pyrazine and 1,3-bis(4...
Show moreThe presence of multiply bonded dimetal units in materials offers opportunities for tuning properties of solids. Materials containing molybdenum-molybdenum quadruple bonds have recently begun being reported. This thesis reports the products of the reactions of dimethyl sulfide (DMS), acetonitrile (ACN) and acetate complexes, Mo2CI4(DMS)4, Mo2(ACN)10ABF4, and Mo2(0Ac)4 with 2,2';6,2"-terpyridine, 4'-phenyl 2,2';6,2"-terpyridine, 2,3,5,6-tetrakis (alpha-pyridyl) pyrazine and 1,3-bis(4-methylimino)isoindoline. Among these ligands, 2,3,5,6-tetrakis (alpha-pyridyl) pyrazine may lead to linear arrays of metal-metal bonds as well as other ordered structures. 1H-NMR, electronic absorption, and infrared data will be quoted to support any structural assignments.
Show less - Date Issued
- 1995
- PURL
- http://purl.flvc.org/fcla/dt/15212
- Subject Headings
- Molybdenum compounds, Metal-metal bonds, Electronic structure
- Format
- Document (PDF)
- Title
- Synthesis of Fluorogenic Probes Specific for Matrix Metalloproteinase 13.
- Creator
- Ibrahim, Mariam, Fields, Gregg B., Leventouri, Theodora, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Matrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity...
Show moreMatrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity and selectivity of MMP-13 and other MMPs against these probes were studied through two approaches. It was found that these probes were cleaved by all MMPs, but MMP-13 showed the highest activity and selectivity towards these peptides.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013507
- Subject Headings
- Matrix Metalloproteinases, Peptides, Fluorogenic probes
- Format
- Document (PDF)
- Title
- The synthesis of bis(dimolybdenum)-1,3,5,7-tetrakis(2-pyridylimino) benzodipyrrole as a precursor for an inorganic, quadruple bond containing polymer.
- Creator
- Kavanaugh, David John, Florida Atlantic University, Baird, Donald M., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
The planar, dinuclear, tridentate ligands, 1,3,5,7-tetrakis(2-pyridylimino)benzodipyrrole (TAII) and 1,3,5,7-tetrakis(4,6-dimethyl-2-pyridylimino)benzodipyrrole (DiMeTAII) were synthesized and characterized as were all intermediates characterized by both infrared and 1H-NMR spectra. Evidence is presented for the formation of Mo4(OAc)6-(DiMeTAII) (I), the dinuclear analog of Mo2(OAc)3-BAII using UV/Vis to show the delta--->delta* transition typical of the quadruple bond and for the...
Show moreThe planar, dinuclear, tridentate ligands, 1,3,5,7-tetrakis(2-pyridylimino)benzodipyrrole (TAII) and 1,3,5,7-tetrakis(4,6-dimethyl-2-pyridylimino)benzodipyrrole (DiMeTAII) were synthesized and characterized as were all intermediates characterized by both infrared and 1H-NMR spectra. Evidence is presented for the formation of Mo4(OAc)6-(DiMeTAII) (I), the dinuclear analog of Mo2(OAc)3-BAII using UV/Vis to show the delta--->delta* transition typical of the quadruple bond and for the determination of percent molybdenum which is consistent with the proposed structure. A review of recent studies into the field of quadruply bonded metal containing polymers will be discussed along with application of compound (I) in this field.
Show less - Date Issued
- 1993
- PURL
- http://purl.flvc.org/fcla/dt/14950
- Subject Headings
- Ligands (Biochemistry), Metal-metal bonds, Diffusion bonding (Metals)
- Format
- Document (PDF)
- Title
- The synthesis of a new polymeric ligand poly[5-(1,3-bis-(2'-pyridylimino)isoindolyloxy)ethylene] (PBPIIIOE).
- Creator
- Jiang, Yi, Florida Atlantic University, Carraher, Charles E., Baird, Donald M., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
A new polymeric ligand, poly[5-(1,3-bis-(2'-pyridylimino) isoindolyloxy)ethylene], was synthesized. At same time, 1,3-bis-(2 '-pyridylimino)-5-hexadecanyloxyisoindoline was also synthesized. These two products were characterized with fourier transform infrared spectrometry, ultraviolet spectrometry, mass spectral analysis and elemental analysis. Their complexes of Cu+2 were prepared.
- Date Issued
- 2000
- PURL
- http://purl.flvc.org/fcla/dt/12663
- Subject Headings
- Ligands, Organometallic polymers
- Format
- Document (PDF)
- Title
- Synthesis and testing the intermediacy of diketopiperazines in the biosynthesis of ecteinascidins.
- Creator
- Jeedigunta, Shanti, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
-
Ecteinascidin 743 is a trace secondary metabolite isolated from the marine tunicate, Ecteinascidia turbinata. Ecteinacidin 743 a most potent antitumor agent, is currently in Phase II clinical trials in Europe and in the USA. A cell-free extract of Ecteinascidia turbinata was used to investigate the biogenetic origin of the ecteinascidins. Incubation experiments with radiolabeled diketopiperazines indicated that the diketopiperazine of tyrosine is the first committed intermediate in the...
Show moreEcteinascidin 743 is a trace secondary metabolite isolated from the marine tunicate, Ecteinascidia turbinata. Ecteinacidin 743 a most potent antitumor agent, is currently in Phase II clinical trials in Europe and in the USA. A cell-free extract of Ecteinascidia turbinata was used to investigate the biogenetic origin of the ecteinascidins. Incubation experiments with radiolabeled diketopiperazines indicated that the diketopiperazine of tyrosine is the first committed intermediate in the biosynthesis of ecteinascidins. Phenylalanine diketopiperazine was not transformed into the ecteinascidins indicating that this cyclic dipeptide is not an intermediate in the biosynthesis of ecteinascidins. The diketopiperazine of DOPA was used as a cold carrier demonstrating that the diketopiperazine of tyrosine is oxidized to DOPA diketopiperazine and then further transformed to the ecteinascidins.
Show less - Date Issued
- 2000
- PURL
- http://purl.flvc.org/fcla/dt/15754
- Subject Headings
- Sea squirts, Dopa, Tunicata
- Format
- Document (PDF)
- Title
- Synthesis and structural characterization of intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease.
- Creator
- Chamely-Wiik, Donna M., Florida Atlantic University, Haky, Jerome E., Carraher, Charles E., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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We have synthesized intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease. A synthetic strategy was devised to be more reproducible than the original strategy. We discovered some very interesting chemistry of one of the intermediates produced from this new scheme. We synthesized L-N-(butyloxycarbonyl)-3-(3-hydroxy-ethyl-4-(benzyloxy)-phenyl)alanine benzylester, a compound containing a secondary alcohol moiety that...
Show moreWe have synthesized intermediates towards the preparation of a polyphosphonate ester containing L-dopa for the potential treatment of Parkinson's disease. A synthetic strategy was devised to be more reproducible than the original strategy. We discovered some very interesting chemistry of one of the intermediates produced from this new scheme. We synthesized L-N-(butyloxycarbonyl)-3-(3-hydroxy-ethyl-4-(benzyloxy)-phenyl)alanine benzylester, a compound containing a secondary alcohol moiety that had a unique set of characteristics. Upon reduction of the N-(tert-butyloxycarbonyl)-3-(3-acetyl-4-benzyloxyphenyl)-L-alanine benzylester, which contained a ketone moiety, to produce the secondary alcohol, we discovered that the materials that were formed included a pair of diastereomers of the secondary alcohol, each diastereomer also exhibiting two individually stable conformational isomers. We believe that the conformational isomers were generated by rotation of the C-N bond of the BOC carbamate, and were so stable that they could be separated by HPLC and NMR techniques. Energy optimization studies and molecular modeling techniques were performed using HyperChem, and rotational barrier energy values were calculated for the different conformational isomers for each of the diastereomers. HPLC and NMR techniques were also used to obtain information about these materials. Using the calculated data from these studies, and analyzing the HPLC chromatograms and NMR spectra we were able to fully determine the assignments for the diastereomers and the individual conformational isomers. We discovered that the SS form was synthesized preferentially over the SR form and that in both cases the E conformation was energetically more stable than the Z form. Octanol/water partition coefficient values (Log P0ct) were also determined and compared to L-dopa and dopamine. We concluded that the values for the dimeric compound that we synthesized and many of its potential products of degradation were significantly higher than that for both L-dopa and dopamine. This may be an indication that this material has a higher degree of lipophilicity than L-dopa itself, having more potential to cross the blood brain barrier. We believe that these intermediate materials serve as good indication of how a polyphosphonate ester containing L-dopa would compare as a potential drug for Parkinson's disease.
Show less - Date Issued
- 2004
- PURL
- http://purl.flvc.org/fcla/dt/12108
- Subject Headings
- Parkinson's disease--Treatment, Antiparkinsonian agents, Dopa, Organophosphorus compounds--Synthesis, Chemistry, Analytic
- Format
- Document (PDF)
- Title
- Synthesis and photophysical measurements of a series of lanthanide-benzenedicarboxylate coordination polymers.
- Creator
- Clark, Jessica Montressa., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Within solid-state chemistry, coordination polymers have gained interest for use in various applications such as sensing, catalysis, display technology, hydrogen storage, etc. The use of lanthanide ions in these materials provides a mean of exploring how structure may affect luminescence efficiency. In this study, the photophysics of several lanthanide benzenecarboxylates was studied. This data combined with data from other coordination polymers created in our lab indicate that the...
Show moreWithin solid-state chemistry, coordination polymers have gained interest for use in various applications such as sensing, catalysis, display technology, hydrogen storage, etc. The use of lanthanide ions in these materials provides a mean of exploring how structure may affect luminescence efficiency. In this study, the photophysics of several lanthanide benzenecarboxylates was studied. This data combined with data from other coordination polymers created in our lab indicate that the established guidelines for producing highly efficient materials may not correlate directly from solution to the solid state and that structure may also play a role.
Show less - Date Issued
- 2013
- PURL
- http://purl.flvc.org/fcla/dt/3362332
- Subject Headings
- Rare earth metals catalysts, Metallic composites, Speciation, Lanthanide shift reagents, Organic compounds, Synthesis, Polymers, Biotechnology
- Format
- Document (PDF)
- Title
- Synthesis and new reactions of allenyl carbonyls: studies towards the total synthesis of anti-thrombotic natural products Vitisinol D and C.
- Creator
- Maity, Pradip., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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We report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method...
Show moreWe report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique monoand dianion mechanisms which are described. Our design of a Morita-Baylis-Hilman (MBH) reaction to include a fast silyl 1,3- Brook rearrangement has enabled the first ever anion-catalysis. This new reaction makes possible the addition of both aliphatic and aromatic aldehydes to s ilylallenes leading to carbinol allenoates. These new MBH reactions products allow for a fasttracked synthesis of [3.2.1] bisoxa-bicycles which make up the framework of many biologically active natural products including Vitisinol D. The development of cyclic addition of hydrazine nitrogen to unactivated alkynes catalyzed by non-metals is reported. Starting from readily accessible silyl allenyl esters, alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles were also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway., The racemic synthesis of fully functionalized bicyclic core of Vitisinol D was achieved using allenyl ester as a key intermediate. The required electron withdrawing group (EWG) at the position was screened for better addition followed by the compatibility towards successive transformation and, finally, the ease of removal. A reductive aldol method to transform lactone-enol to the desired [3.2.1] bicycle was extensively studied to understand the stereoelectronic requirements for the formation of such bicyclic structures. Due to the necessity of selective protection and deprotection of many phenolic and aliphatic hydroxyls as well as ester groups, orthogonal protecting groups were established accordingly.
Show less - Date Issued
- 2011
- PURL
- http://purl.flvc.org/FAU/3332717
- Subject Headings
- Organic compounds, Synthesis, Carbonyl compounds, Synthesis, Cardiovascular system, Diseases, Treatment
- Format
- Document (PDF)
- Title
- Synthesis and In Vitro Evaluation of Some Novel Nucleoside analogs and DNA lntercalators as Potential Anticancer or Antiviral Agents.
- Creator
- Zhao, Yuxiang, Florida Atlantic University, Parkanyi, Cyril, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Thiadiazoles can be considered as analogs of pyrimidines because of the well known analogy between a -CH=CH- group in benzenoid hydrocarbons and bivalent sulfur, -S-, in aromatic heterocycles. Therefore, 5-amino-2H-1 ,2,4-thiadiazole-3-one and 5-amino-3H-1 ,3,4-thiadiazole-2-one are the analogs of cytosine. In our first project, the preparation of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1 ,2,4- thiadiazol-3-one (1), 5-amino-2-(tetrahydrofuran-2-yl)-1 ,2,4-thiadiazol-3...
Show moreThiadiazoles can be considered as analogs of pyrimidines because of the well known analogy between a -CH=CH- group in benzenoid hydrocarbons and bivalent sulfur, -S-, in aromatic heterocycles. Therefore, 5-amino-2H-1 ,2,4-thiadiazole-3-one and 5-amino-3H-1 ,3,4-thiadiazole-2-one are the analogs of cytosine. In our first project, the preparation of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1 ,2,4- thiadiazol-3-one (1), 5-amino-2-(tetrahydrofuran-2-yl)-1 ,2,4-thiadiazol-3-one (2), 5- amino-3-((2' -hydroxyethoxy)methyl)-1 ,3,4-thiadiazol-2-one (3), 5-amino-3-( 4' -hydroxy- 2' -hydroxyrnethyl-butyl)-1 ,3,4-thiadiazole-2-thione ( 4), (R)-5-am ino-3-(2' ,3' - dihydroxypropyl)-1 ,3,4-thiadiazole-2-thione (5), and (S)-5-amino-3-(2' ,3 ' - dihydroxypropyl )-1 ,3,4-thiadiazole-2-thione (6). (R)-5-amino-3-(2' ,3' -dihydroxypropyl)-1,3,4-thiadiazole-2-thione (5) and (S)-5-amino-3-(2' ,3' -dihydroxypropyl)-1 ,3,4- thiadiazole-2-thione (6) are stereoisomers. Their racemic mixture 7 was also prepared and tested. The synthesis, characterization, and properties of these new synthesized thiadiazole derivatives are discussed. A dimerization of 5-amino-3H-1 ,3 ,4-thiadiazole-2- thione (18) to produce di-(5-amino-1 ,3,4-thiadiazol-2-yl) disulfide (23) by sodium nitrite with either acetic acid or stannic chloride is also reported. Preliminary results indicate that 3 and 23 possess antimicrobial activity. In the second project, the synthesis of three series of bis-aminochloropyrimidine derivatives with different types of linkers as potential DNA intercalators is described. The first series are aminochloropyrimidines bridged by polyrnethylene chain linkers with various lengths. The second series are bridged by polyether linkers to lower the lipophilicity. The third series are bridged by linkers containing benzene rings to limit the flexibility. The spectral data and other physical properties of the new compounds are discussed. The preliminary screening results indicate that many new synthesized bisintercalators are biologically active. The relationship between bioactivity and structure is discussed as well.
Show less - Date Issued
- 2007
- PURL
- http://purl.flvc.org/fau/fd/FA00000886
- Subject Headings
- Biopharmaceutics, Antineoplastic agents--Pharmacodynamics, Nucleosides--Metabolism, Pharmaceutical chemistry, Antiviral agents--Synthesis
- Format
- Document (PDF)
- Title
- Synthesis and characterization of tin-containing polymers derived from amino acids.
- Creator
- Li, Fengmai, Florida Atlantic University, Carraher, Charles E., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Tin-containing polymers were synthesized by reaction of amino acids (4-aminobenzoic acid, ampicillin, glycylglycine and glycyl-D-phenylalanine) with organotin dichloride via the interfacial condensation technique. The products were characterized using Fourier Transform Infrared spectrometry, Ultraviolet spectrometry, light scattering photometry and mass spectral analysis. The biological activities of the products were tested against selected microorganisms and human cells.
- Date Issued
- 1998
- PURL
- http://purl.flvc.org/fcla/dt/15611
- Subject Headings
- Organometallic polymers, Organotin compounds
- Format
- Document (PDF)
- Title
- Synthesis and characterization of polyazo-group IVB metallocene dichloride derivatives.
- Creator
- Kloss, John Edward, Florida Atlantic University, Carraher, Charles E., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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Reaction of Group IVB metallocene dichlorides with a monoaza dye yields a polymer in which the metal is bonded to a sulfonic and a hydroxyl group. The structure and bonding of the polymer was confirmed using infrared, mass spectrometry and 1H-NMR spectroscopy. Thermo and elemental analysis was used to confirm the presence of the metal. The stability of the polydye to the monomer unit was compared employing an argon laser in the visible region.
- Date Issued
- 1993
- PURL
- http://purl.flvc.org/fcla/dt/14912
- Subject Headings
- Metallocenes, Organometallic polymers, Infrared spectroscopy, Azo compounds
- Format
- Document (PDF)
- Title
- Synthesis and Characterization of Organotin Polyamine Esters from Diglycine.
- Creator
- Slawek, Paul Peter, Carraher, Charles E., Haky, Jerome E., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
- Abstract/Description
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This research is part of a long-term project aimed at elucidating important structural features, of both ligands and metals, that are needed to produce effective anti-cancer agents. The specific goal is the synthesis of organotin polymers containing amino acids, in this case the diamino acid diglycine. The desired materials were synthesized with percent yields ranging from 32-99%. The products were synthesized employing the interfacial polymerization technique. The polymers were then...
Show moreThis research is part of a long-term project aimed at elucidating important structural features, of both ligands and metals, that are needed to produce effective anti-cancer agents. The specific goal is the synthesis of organotin polymers containing amino acids, in this case the diamino acid diglycine. The desired materials were synthesized with percent yields ranging from 32-99%. The products were synthesized employing the interfacial polymerization technique. The polymers were then characterized utilizing the following physical characterization techniques: light scattering photometry (LS), Infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), and matrix assisted laser desorption mass spectroscopy (MALDI). Physical characterization showed evidence of formation of desired adducts in addition to data that was consistent with the formation of materials containing multiple repeat units. The materials were then analyzed for biological activity. The synthesized materials displayed the ability to inhibit tested cancer cell lines.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013158
- Subject Headings
- Organotin Compounds, Glycylglycine, Antineoplastic agents--Development
- Format
- Document (PDF)