Kattesh V Katti
University of Missouri-Columbia, Radiology, Faculty Member
- Globally recognized as the ‘Father of Green Nanotechnology’, Professor Kattesh V. Katti, MSc Ed, PhD, DSc, FRSC, FNA... moreGlobally recognized as the ‘Father of Green Nanotechnology’, Professor Kattesh V. Katti, MSc Ed, PhD, DSc, FRSC, FNAI, Curators’ Professor of Radiology, Director, Institute of Green Nanotechnology, within the Medical School, University of Missouri, Columbia, USA—is internationally renowned as a leader in the interconnecting fields of—chemistry, radiopharmaceutical sciences, nanotechnology/green nanotechnology and nanomedicine—for biomedical applications, specifically for molecular imaging and therapy of living subjects. Dr. Katti is a pioneer in the field of Nano-Ayurvedic Medicine—a new medical modality which he has discovered by the application of Green Nanotechnology to Ayurvedic-Holistic Medicine. The US Patents and Trademarks office has approved the use of ‘Nano-Ayurvedic Medicine’ name in the products of this new medical modality. Several cancer therapy products and antibiotics, discovered by Dr. Katti, are currently used in treating human patients. National Academy of Inventors—the largest Inventors Academy of the World has recently produced a documentary on Dr. Katti’s inventions which are used for combating COVID and related deadly infections: https://www.youtube.com/watch?v=-OVI33BFMtkedit
The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research... more
The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing op...
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Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when... more
Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the 198 Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible 198 AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nano...
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Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular... more
Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular imaging and therapy. Bombesin (BBN) peptides have demonstrated high affinity toward gastrin-releasing peptide (GRP) receptors in vivo that are overexpressed in prostate, breast, and small-cell lung carcinoma. We have synthesized a library of GRP receptor-avid nanoplatforms by conjugating gold nanoparticles (AuNPs) with BBN peptides. Cellular interactions and binding affinities (IC 50 ) of AuNP–BBN conjugates toward GRP receptors on human prostate cancer cells have been investigated in detail. In vivo studies using AuNP–BBN and its radiolabeled surrogate 198 AuNP–BBN, exhibiting high binding affinity (IC 50 in microgram ranges), provide unequivocal evidence that AuNP–BBN constructs are GRP-receptor-specific showing accumulation with high selectivity in G...
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Chelating frameworks based on hydroxymethylene phosphine (HMP) functionalities provides a novel approach to produce chelate-conjugates compatible with development of new Tc-99m and Re-186/188 radiopharmaceuticals. Studies with a bombesin... more
Chelating frameworks based on hydroxymethylene phosphine (HMP) functionalities provides a novel approach to produce chelate-conjugates compatible with development of new Tc-99m and Re-186/188 radiopharmaceuticals. Studies with a bombesin conjugate demonstrates the potential of using HMP-based chelating frameworks to develop radiolabeled receptor-avid agents for targeting cancers.
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Research Interests: Chemistry, Medicine, Humans, Mice, Animals, and 14 moreHigh Performance Liquid Chromatography, Clinical Sciences, Phosphine, In Vivo, Technetium, Water soluble polymers, Cysteine, In Vitro Studies, Radiopharmaceuticals, Histidine, Molecular Structure, Serum albumin, Tissue distribution, and Human serum albumin
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The bidentate, water-soluble phosphine ligands, bis(bis(hydroxymethyl)phosphino)benzene (HMPB, 1) and bis(bis(hydroxymethyl)phosphino)ethane (HMPE, 2) were reacted with the organometallic precursor fac-[ReBr(3)(CO)(3)](2-), 3, to produce... more
The bidentate, water-soluble phosphine ligands, bis(bis(hydroxymethyl)phosphino)benzene (HMPB, 1) and bis(bis(hydroxymethyl)phosphino)ethane (HMPE, 2) were reacted with the organometallic precursor fac-[ReBr(3)(CO)(3)](2-), 3, to produce the complexes fac-[Re(OH(2))(CO)(3)L](+) and fac-[ReBr(CO)(3)L] (L = HMPE, HMPB), respectively, in good yields. The rhenium complexes fac-[ReBr(CO)(3)HMPB], 5, and fac-[ ReBr(CO)(3)HMPE], 8, were characterized using (1)H and (31)P NMR spectroscopy. The structure of fac-[ReBr(CO)(3)HMPB] was confirmed by single-crystal X-ray spectroscopy. The substitution reactions of HMPE/HMPB with the rhenium precursor 3 in aqueous solution were monitored using time-dependent (31)P NMR techniques. A significant discrepancy in the reaction kinetics and the substitution mechanism between the two bidentate ligands could be observed presumably due to the different chemical backbones.
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Recent progress in the synthesis of water-soluble phosphine ligand systems and their corresponding 99mTc complexes prompted the development of a new bifunctional chelating agent (BFCA) based on a tetradentate dithiadiphosphine framework... more
Recent progress in the synthesis of water-soluble phosphine ligand systems and their corresponding 99mTc complexes prompted the development of a new bifunctional chelating agent (BFCA) based on a tetradentate dithiadiphosphine framework (P2S2-COOH). The detailed synthesis of this new BFCA is described here. The corresponding 99mTc complex, 99mTc-P2S2-COOH, can be formed in >95% yield. To demonstrate the potential of this chelate to efficiently label peptides, 99mTc-P2S2-COOH was coupled to the N-terminal region of the truncated nine-amino acid bombesin analogue, 5-Ava-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 [BBN(7-14)], to form 99mTc-P2S2-BBN(7-14). Conjugation to the peptide was performed in borate buffer (pH 8.5) by applying the prelabeling approach in yields of >60%. In competitive binding assays, using Swiss 3T3 mouse fibroblast cells against [125I-Tyr4]bombesin, Re-P2S2-BBN(7-14) exhibited an IC50 value of 0.8 +/- 0.4 nM. The pharmacokinetic studies of 99mTc-P2S2-BBN(7-14) and its ability to target tissue expressing gastrin-releasing peptide (GRP) receptors were performed in normal mice. The 99mTc-P2S2-BBN(7-14) exhibited fast and efficient clearance from the blood pool (0.6 +/- 0.1% ID, 4 h postinjection) and excretion through the renal and hepatobiliary pathways (56.4 +/- 8.2 and 28.1 +/- 7.9% ID, 4 h postinjection, respectively). Significant uptake in the pancreas was observed (pancreatic acini cells express bombesin/GRP receptors), producing pancreas:blood and pancreas:muscle ratios of ca. 22 and 80, respectively, at 4 h postinjection.
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The goal of our study was to demonstrate the utility of nanocrystalline gold as an X-ray contrast agent for imaging tumor in living subjects. Even though significant progress has been achieved in this area by researchers, clinical... more
The goal of our study was to demonstrate the utility of nanocrystalline gold as an X-ray contrast agent for imaging tumor in living subjects. Even though significant progress has been achieved in this area by researchers, clinical translation remains challenging. Here, we investigated biocompatible gum Arabic stabilized gold nanocrystals (GA-AuNPs) as X-ray contrast agent in tumor bearing mice and dog. Single intratumoral injections of GA-AuNP resulted in X-ray contrast change of -26 HU in the tumor region after 1 hour post-injection period. Subsequently, five intratumoral injections were performed in the mice. The change in CT number in tumor region is not progressive; rather it reaches a saturation point after fourth injection. These data suggested that accumulation of GA-AuNP reaches a threshold limit within a short time period (5 h), and is retained in the tumor tissue for the rest of the period of investigation. A pilot study was conducted in a client-owned dog presented with collision tumor of thyroid carcinoma and osteosarcoma. In this study, GA-AuNP was injected intratumorally in dog and a contrast enhancement of 12 deltaHU was observed. The CT images of both mice and dog clearly demonstrated that GA-AuNP was effectively distributed and retained throughout the tumor site. The CT data obtained by the present study would provide the crucial dosimetry information for strategic therapy planning using this construct. Both mice and dog did not show any clinical changes, thereby confirming that GA-AuNP did not induce toxicity and can be explored for future clinical applications.
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The application of nanotechnology in nuclear medicine offers attractive therapeutic opportunities for the treatment of various diseases, including cancer. Indeed, nanoparticles-conjugated targeted alpha-particle therapy (TAT) would be... more
The application of nanotechnology in nuclear medicine offers attractive therapeutic opportunities for the treatment of various diseases, including cancer. Indeed, nanoparticles-conjugated targeted alpha-particle therapy (TAT) would be ideal for localized cell killing due to high linear energy transfer and short ranges of alpha emitters. New approaches in radiolabeling are necessary because chemical radiolabeling techniques are rendered sub-optimal due to the presence of recoil energy generated by alpha decay, which causes chemical bonds to break. This review attempts to cover, in a concise fashion, various aspects of physics, radiobiology, and production of alpha emitters, as well as highlight the main problems they present, with possible new approaches to mitigate those problems. Special emphasis is placed on the strategies proposed for managing recoil energy. We will also provide an account of the recent studies in vitro and in vivo preclinical investigations of α-particle therapy...
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A. Y. Al-Yasiri,a M. Khoobchandani,b C. S. Cutler,c L. Watkinson,d T. Carmack,d C. J. Smith,e M. Kuchuk,f S. K. Loyalka,a* A. B. Lugão,g and K. V. Katti,h* aNuclear Science and Engineering Institute (NSEI), University of Missouri,... more
A. Y. Al-Yasiri,a M. Khoobchandani,b C. S. Cutler,c L. Watkinson,d T. Carmack,d C. J. Smith,e M. Kuchuk,f S. K. Loyalka,a* A. B. Lugão,g and K. V. Katti,h* aNuclear Science and Engineering Institute (NSEI), University of Missouri, Columbia, MO 65211, USA bDepartment of Radiology, Institute of Green Nanotechnology, University of Missouri, One Hospital Drive, Columbia, MO, 65212, USA cNuclear Science and Engineering Institute (NSEI), University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65211, USA dHarry S. Truman Memorial Veterans Hospital, University of Missouri, One Hospital Drive, Columbia, MO, 65212, USA eDepartment of Radiology, Harry S. Truman Memorial Veterans Hospital, University of Missouri, One Hospital Drive, Columbia, MO, 65212, USA fUniversity of Missouri Research Reactor (MURR), University of Missouri, One Hospital Drive, Columbia, MO, 65212, USA gNuclear and Energy Research Institute – IPEN/CNEN/Sao Paulo, Brazil hNuclear Science and Engi...
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Introduction We report, herein, in vitro, and in vivo toxicity evaluation of silver nanoparticles stabilized with gum arabic protein (AgNP-GP) in Daphnia similis, Danio rerio embryos and in Sprague Dawley rats. Purpose The objective of... more
Introduction We report, herein, in vitro, and in vivo toxicity evaluation of silver nanoparticles stabilized with gum arabic protein (AgNP-GP) in Daphnia similis, Danio rerio embryos and in Sprague Dawley rats. Purpose The objective of this investigation was to evaluate in vitro and in vivo toxicity of silver nanoparticles stabilized with gum arabic protein (AgNP-GP), in multispecies due to the recognition that toxicity evaluations beyond a single species reflect the environmental realism. In the present study, AgNP-GP was synthesized through the reduction of silver salt using the tri-alanine-phosphine peptide (commonly referred to as “Katti Peptide”) and stabilized using gum arabic protein. Methods In vitro cytotoxicity tests were performed according to ISO 10993–5 protocols to assess cytotoxicity index (IC50) values. Acute ecotoxicity (EC50) studies were performed using Daphnia similis, according to the ABNT NBR 15088 protocols. In vivo toxicity also included evaluation of acute e...
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Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as... more
Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the differentiation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticles (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of antitumor cytokines (IL-12 and TNF-) with concomitant reductions in the levels of pro-tumor cytokines (I...
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Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants... more
Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants contain phytochemicals that has been used traditionally for treatment of various diseases, and proved to be non-toxic to healthy tissues. These phytochemicals play an important role in bio-reduction processes as reducing and stabilizing agents, and renders NPs selective toxicity towards diseased tissues. The study reports on the synthesis of AuNPs using Acai berry (AB) and Elderberry (EB) extracts and their anti-cancer properties. Formation of berry-AuNPs was confirmed through measurement of physico-chemical properties. The stability of the AuNPs was tested in biocompatible solutions. Anti-cancer activity of berry extracts and AuNPs was evaluated on the prostate (PC-3) and pancreatic (Panc-1) cancer cells. The berry extracts did not show toxicity t...
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The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological... more
The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological diseases such as acne. Acne is defined as a chronic inflammatory disorder based on its ability to persist for long periods throughout an individual’s life. The synthesis of gold nanoparticles (AuNPs) was performed using the bottom-up approach by reduction of a gold salt (HAuCl4.3H2O) by the methanol extract (HO-MeOH) and aqueous decoction prepared from the dried aerial parts of Helichrysum odoratissimum (HO-Powder). The HO-MeOH and HO-Powder AuNPs were prepared as unstabilised (−GA) or stabilized (+GA) by the omission or addition of Gum Arabic (GA) as the capping agent. The characterization of the AuNPs was performed using Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), Ultraviolet-Visual spectroscopy (UV-Vis), Thermogravimetri...
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We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to... more
We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-(198)AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin induced in mice which overexpress this receptor subtype. Detailed in vivo therapeutic efficacy studies, through the intratumoral delivery of MGF-(198)AuNPs, show the retention of over 80% of the injected dose (...
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In our previous work, we have extensively evaluated the physiochemical characteristics of Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs; 15-18nm) and reported their effectiveness in stopping the tumor initiation via inhibiting the... more
In our previous work, we have extensively evaluated the physiochemical characteristics of Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs; 15-18nm) and reported their effectiveness in stopping the tumor initiation via inhibiting the pre-neoplastic lesions in liver. The rationale of this study is to detect the efficiency of using GA-AuNPs in photothermal application as a non-invasive technique against lung tumor. We investigated the cytotoxicity of GA-AuNPs on A549 cells, and then studied their apoptotic, anti-inflammatory, lipid peroxidation and anti-neovascular effect in in vivo model using a chemically-induced lung cancer in mice. The histopathological changes due to GA-AuNPs were investigated. In the presence of laser irradiation, GA-AuNPs had a considerable cytotoxicity against A549 cells. The treatment of lung tumor-bearing mice with GA-AuNPs followed by laser exposure enhanced the apoptotic pathway and this was obvious from the histopathological investigations and the ele...
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This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model.... more
This study validates the utility of Gum Arabic-conjugated gold nanoparticles (GA-AuNPs) and laser to induce photothermal inhibition of hepatocarcinogenesis, via employing a diethylnitrosamine (DEN)-mediated hepatocellular carcinoma model. This work included both of in vitro and in vivo studies; to investigate the GA-AuNPs cytotoxicity and phototoxicity in hepatic cell line; to delineate the GA-AuNPs therapeutic efficiency in DEN-induced preneoplastic lesions (PNLs) in the liver of Balb-C mice. The therapeutic effects of GA-AuNPs on the mediators of apoptosis, inflammation, and tumor initiation, as well as the histopathological changes in preneoplastic liver have been investigated. Our results infer that GA-AuNPs in combination with laser irradiation led to a significant reduction in the cell viability and in histone deacetylase activity in hepatocarcinoma HepG2 cells. In chemically-induced PNLs mice model our results have demonstrated that GA-AuNPs, with or without laser irradiation, induced cancer cell apoptosis through the activation of death receptors DR5 and caspase-3 and inhibited both of the PNLs incidence and the initiation marker (placental glutathione S-transferase; GST-P). The laser-stimulated GA-AuNPs significantly reduced the tumor necrosis factor-α levels. In summary, GA-AuNPs with laser treatment inhibited liver PNLs via the induction of the extrinsic apoptosis pathway and the inhibition of inflammation.
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... Stabilized Fischer Carbenes Hanadi F. Sleiman, Bruce A. Arndtsen, and Lisa McElwee-White" Department of Chemistty, Stanford Universiw, Stanford, California 94305 Received December 18. 1990 Summary: The low-valent ...
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New approaches to heteroatomic chelation of early and late transition metals. Synthesis and characterization of cyclometallaphosphosphoranimine- and cyclometallaphosphoraniminatophosphanes (and arsanes) of Mo(O), W(O), Rh(I), and Ir(I) derived from novel heterodifunctional phosphorus and arsenic ...more
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ABSTRACT Nanotechnology and the various properties of gold nanoparticles (AuNPs) are quickly changing the field of cancer detection and treatment. Photoacoustic detection methods show an increase in sensitivity using gold nanoparticle... more
ABSTRACT Nanotechnology and the various properties of gold nanoparticles (AuNPs) are quickly changing the field of cancer detection and treatment. Photoacoustic detection methods show an increase in sensitivity using gold nanoparticle antibody conjugation, which selectively targets melanoma cancer cells. Instead of targeting melanoma tumors, we tag single cells, analogous to circulating metastatic melanoma cells. Using an in vitro, stationary cell system and planar samples, we demonstrate an average of 24% improved optical detectability of melanoma cells tagged with AuNPs over unprocessed melanoma cells. Tagged cells showed a raised plateau of absorbance from 470nm to 550nm. Untagged cells showed a general decline in absorption as wavelength increased. The results of our study have the potential to not only better develop photoacoustic detection of melanoma, but also extend the viability and use of photoacoustics into detection of otherwise unpigmented cancers.
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Transition Metal Chemistry of Main Group Hydrazides. Part 16: (Phosphanyl)hydrazines R2PN(Me)N(Me)PR2 As a Novel Class of Chelating Bis(phosphines). Synthesis, Coordination Chemistry, and X-ray Structures of cis-[PdCl2{(p-BrC6H4O)2PN- (Me)N(Me)P(OC6H4Br-p)2}] and cis-[W(CO)4{(PhO)2PN(Me)N(Me)P(OP...more
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Transition Metal Chemistry of Main Group Hydrazides. 8. A new Long-Chain Diphosphine with the PIII-N-N-PV-N-N-PIII Backbond as a Chelating Ligand for Molybdenum, Platinum, and Palladium. Crystal and Molecular Structures of cis-[Mo(CO)4{PhP(S)[N(Me)NHP(i-Pr)2]2}] and cis-[PtCl2{PhP(S)[N(Me)NHP(i-P...more
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Transition metal chemistry of main group hydrazides. 4. Phosphorus hydrazido ferrocenes as novel synthons to new iron(II)-palladium(II) heterotrimetallic organometallic compounds. Synthesis and characterization of palladium(II) chloride complexes of ferrocene functionalized phosphorus hydrazides....more
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Transition metal chemistry of main group hydrazides. IV: Phosphorus hydrazido ferrocenes as novel synthons to new iron(II)-palladium(II) heterotrimetallic organometallic compounds. Synthesis and characterization of palladium(II) chloride complexes of ferrocene functionalized phosphorus hydrazides...more