Carboxylato compounds of chromium, copper, rhodium and molybdenum and new advances in the chemistry of V2(NXN)4

This dissertation comprises the investigation of two subjects in the field of dimetal paddlewheel-type compounds containing metal-metal bonds: unsolvated transition metal carboxylates and triply bonded divanadium compounds. The first subject is very mature; dichromium tetraacetate was first synthesized in 1844, and hundreds of dimetal tetracarboxylates have been structurally characterized to date. A general question concerning the complexes of the type M2L4-Xn (where n = 0 to 2) is the extent to which the M-M distances are influenced by the presence of axial ligands, X. However, virtually none of the carboxylato complexes crystallize without axial ligands. In the solid state, in the absence of a coordinating solvent, the dimetal units often act as axial ligands to one another. In order to exclude axial coordination, both from donor solvent molecules, and from the aggregation of M24+ units, we have successfully used the bulky 2,4,6-triisopropylbenzoate ligand to bridge the dimetal core. We have investigated the triisopropylbenzoato complexes of some metals which are known for their ability to form a vast array of tetracarboxylato complexes, namely chromium, copper, molybdenum, and rhodium, and have found that these novel compounds display some interesting structural and chemical properties. The second subject of this dissertation is much more contemporary. Although compounds containing multiple bonds between metal atoms have been known since 1964, the first triply-bonded divanadium compound was not synthesized until 1992, and only two additional compounds of this type have been made in the intervening ten years. In order to extend this chemistry, several additional compounds containing a triply bonded V24+ core have recently been characterized. In our study of these compounds, we have discovered the first example of a stable paddlewheel-type compound with a M23+ core

Carboxylato compounds of chromium, copper, rhodium and molybdenum and new advances in the chemistry of V2(NXN)4

This dissertation comprises the investigation of two subjects in the field of dimetal paddlewheel-type compounds containing metal-metal bonds: unsolvated transition metal carboxylates and triply bonded divanadium compounds. The first subject is very mature; dichromium tetraacetate was first synthesized in 1844, and hundreds of dimetal tetracarboxylates have been structurally characterized to date. A general question concerning the complexes of the type M2L4-Xn (where n = 0 to 2) is the extent to which the M-M distances are influenced by the presence of axial ligands, X. However, virtually none of the carboxylato complexes crystallize without axial ligands. In the solid state, in the absence of a coordinating solvent, the dimetal units often act as axial ligands to one another. In order to exclude axial coordination, both from donor solvent molecules, and from the aggregation of M24+ units, we have successfully used the bulky 2,4,6-triisopropylbenzoate ligand to bridge the dimetal core. We have investigated the triisopropylbenzoato complexes of some metals which are known for their ability to form a vast array of tetracarboxylato complexes, namely chromium, copper, molybdenum, and rhodium, and have found that these novel compounds display some interesting structural and chemical properties. The second subject of this dissertation is much more contemporary. Although compounds containing multiple bonds between metal atoms have been known since 1964, the first triply-bonded divanadium compound was not synthesized until 1992, and only two additional compounds of this type have been made in the intervening ten years. In order to extend this chemistry, several additional compounds containing a triply bonded V24+ core have recently been characterized. In our study of these compounds, we have discovered the first example of a stable paddlewheel-type compound with a M23+ core

A [3]Ferrocenophane polyphenol showing a remarkable antiproliferative activity on breast and prostate cancer cell lines

International audienc

The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells

International audienceWe have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ERα, and between 0.18% and 15.5% for ERβ, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 μM) and antiproliferative at high concentrations (10 μM). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC50 values of 0.8 μM for 2 and 0.65 μM for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols

The replacement of a phenol group by an aniline or acetanilide group enhances the cytotoxicity of 2-ferrocenyl-1,1-diphenyl-but-1-ene compounds against breast cancer cells

International audienceWe have previously shown that conjugated ferrocenyl p-phenols show strong cytotoxic effects against both the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines, possibly via oxidative quinone methide formation. We now present a series of analogous amine and acetamide compounds: 2-ferrocenyl-1-(4-aminophenyl)-1-phenyl-but-1-ene (Z+E-2), 2-ferrocenyl-1-(4-N-acetylaminophenyl)-1-phenyl-but-1-ene (Z-3), and their corresponding organic molecules 1-(4-aminophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-4) and 1-(4-N-acetamidophenyl)-1,2-bis-phenyl-but-1-ene (Z+E-5). All of the compounds have adequate relative binding affinity values for the estrogen receptor; between 2.8% and 5.7% for ERα, and between 0.18% and 15.5% for ERβ, as well as exothermic ligand binding in in silico ER docking experiments. Compounds 2 and 3 show dual estrogenic/cytotoxic activity on the MCF-7 cell line; they are proliferative at low concentrations (0.1 μM) and antiproliferative at high concentrations (10 μM). On the MDA-MB-231 cell line, the ferrocenyl complexes 2 and 3 are antiproliferative with IC50 values of 0.8 μM for 2 and 0.65 μM for 3, while the purely organic molecules 4 and 5 show no effect. Electrochemical experiments suggest that both 2 and 3 can be transformed to oxidized quinoid-type species, analogous to what had previously been observed for the ferrocene phenols

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Ferrocifens and Ferrocifenols as New Potential Weapons against Breast Cancer

Depending on the presence or absence of the estrogen receptor in the cells, breast cancer today is often treated by endocrine therapy (tamoxifen) or chemotherapy, respectively. We present now a new paradigm for breast cancer treatment, taking advantage of concepts in bioorganometallic chemistry. In this way, we have synthesized molecules containing an organometallic moiety (ferrocene), and a biovector (hydroxytamoxifen), yielding compounds which display a new therapeutic spectrum consisting of antiestrogenicity and cytotoxicity. A structure–activity relationship study has shown that a ferrocene group, linked to a para-phenol group by a conjugated spacer, is a necessary motif for strong cytotoxic effects to be observed

Selective estrogen receptor modulators in the ruthenocene series. Synthesis and biological behavior

A series of ruthenocene derivatives, 1-[4-(O(CH2)nN(CH3)2)phenyl]-1-(4-hydroxyphenyl)-2-ruthenocenylbut-1-ene, with n = 2-5, based on the structure of the breast cancer drug tamoxifen has been prepared. These compounds were obtained, via a McMurry cross-coupling reaction, as a mixture of Z and E isomers that could not be separated by HPLC. The relative binding affinity values for estrogen receptor α (ERα) for n = 2 and 3 were very high (85 and 53%) and surpassed even that of hydroxytamoxifen (38.5%), the active metabolite of tamoxifen. Ruthenocene derivatives act as anti-estrogens as effective (n = 2) or slightly more effective (n = 3-5) than hydroxytamoxifen on ERα-positive breast cancer cell lines but, unlike ferrocifens, do not show antiproliferative effects on ERα-negative breast cancer cell lines. Electrochemical studies showed that the ruthenocifen radical cations are unstable, which may account for this behavior. Some of these compounds could be useful as radiopharmaceuticals for ERα-positive breast cancer tumors

Rapid discrimination of crystal handedness by XNCD mapping

An original method for determining the handedness of individual non‐centrosymmetric crystals in a mixture using a tightly‐focused, circularly polarized X‐ray beam is presented. The X‐ray natural circular dichroism (XNCD) spectra recorded at the metal K‐edge on selected crystals of [Δ‐M(en)3](NO3)2 and [Λ‐M(en)3](NO3)2 (M=CoII, NiII) show extrema at the metal pre‐edge (7712 eV for Co, 8335 eV for Ni). A mapping of a collection of some 220 crystals was performed at the respective energies by using left and right circular polarizations. The difference in absorption for the two polarizations, being either negative or positive, directly yielded the handedness of the crystal volume probed by the beam. By using this technique, it was found that the addition of l‐ascorbic acid during the synthesis of [Co(en)3](NO3)2 resulted in an enantiomeric enrichment of the Λ‐isomer of 67±13 %, whereas the Ni analogue was similarly, but conversely, enriched in the Δ‐isomer (65±22 %)

Facile synthesis and strong antiproliferative activity of disubstituted diphenylmethylidenyl-[3]ferrocenophanes on breast and prostate cancer cell lines

International audienceA series of new 1-[di-(4-R-phenyl)-methylidenyl)]-[3]ferrocenophanes, where R = OH, NH2, NHAc, and the phenyl substitution is mixed or identical, are highly antiproliferative against MDA-MB-231 and PC-3 cancer cells, with IC50 values ranging from 0 05-5 6 mu M on MDA-M B-231 and 0 02-12 5 mu M on PC-