Gallium Complexes Research Articles

A Hexanuclear Gallium(III) Complex with a {GaIII6(μ‐OH)10} Core Supported by Two Naphthalenediolate‐Based Ligands

AbstractWe have developed a family of 2,7‐disubstituted 1,8‐naphthalenediol ligands to pre‐organize two metal ions to the distance of two neighboring phosphate diesters of 6–7 Å in the DNA backbone by a rigid backbone. As complexes with divalent ions (CuII and NiII) bind to DNA, interferes DNA synthesis via PCR, and kills human cancer cells more efficiently than human stem cells of the same proliferation rate, we intended to increase the binding affinity by going from divalent to trivalent ions‐especially FeIII. Here, we apply GaIII as redox inactive model for FeIII and obtain for the first time a complex with trivalent ions. However, the structural characterization provides not a dinuclear GaIII complex, but a hexanuclear GaIII complex with a central {GaIII6(μ‐OH)10} core, that is yet unprecedented.

Triscyanocorrole, the Newest and Most Intriguing Member of the C1-Substituted Corrole Family.

Considering the potential advantages of minimally sized corroles for diverse applications, this study reports a facile access to cyano-substituted derivatives via a rare CF3/CN conversion. Investigation of the fully characterized gallium, phosphorus, and cobalt complexes discloses multiple effects of the meso-nitrile groups attached to the macrocycle. This corrole appears to be the most electron poor derivative which comes into play in the redox potentials of the corresponding complexes. Compared to its precursor, both the absorption and emission are strongly red shifted and the fluorescence lifetime and quantum yield are much larger. The coordination chemistry is affected as well, by virtue of axial ligands being perpendicular rather than parallel relative to each other.

Bis(thiosemicarbazide)gallium(III) Complexes as Potent Anticancer Agents by ROS Induction and Mitochondrial Pathway Activation

ABSTRACTA series of bis(thiosemicarbazide)gallium (III) complexes were synthesized and characterized by infrared spectroscopy, mass spectrometry, nuclear magnetic resonance, single‐crystal x‐ray crystallography, and density functional theory (DFT) calculation. The cytotoxicity of these gallium(III) complexes (CP 1–4) was subsequently evaluated against HCT‐116, HeLa, MDA‐MB‐231, and A549 cancer cell lines, as well as the normal cell line LO2, by MTT assays. The results indicated that CP‐1 displayed potent inhibitory effects against human colorectal cancer cells (HCT‐116) (IC50 = 0.03 ± 0.01) and human breast cancer cells (MDA‐MB‐231) (IC50 = 0.02 ± 0.01), significantly outperforming cisplatin. Moreover, CP‐2 exhibited notable selectivity towards MDA‐MB‐231 cells (IC50 = 5.01 ± 0.40) with minimal toxicity towards normal cells. Mechanistic studies revealed that treatment with CP 1–2 led to elevated intracellular reactive oxygen species (ROS) levels, resulting in cell cycle arrest at different phases. Specifically, CP‐1 induced G2/M phase arrest, inhibiting cancer cell proliferation, whereas CP‐2 hindered DNA synthesis (S phase) to impede cell proliferation. Furthermore, both CP‐1 and CP‐2 caused a reduction in mitochondrial membrane potential, activating the mitochondrial apoptotic pathway and inducing apoptosis in cancer cells. Molecular docking experiments demonstrated strong interactions between CP 1–2 and protein disulfide isomerase (PDI) at the molecular level. These findings suggest that CP‐1 and CP‐2 serve as potential anticancer agents, particularly showing promising potential in the treatment of breast cancer.

High-Efficiency Solar Transformation of Sugars via a Heterogenous Gallium(III) Catalyst.

Extremely limited research exploring the photocatalytic potential of main group metals, such as aluminum, gallium, and tin, has been undertaken due to their weak light harvesting properties. This study reports the efficient transformation of sugars to 5-hydroxymethylfurfural (HMF) with high yield employing an original heterogeneous photocatalyst comprising a gallium(III) complex immobilized on an alumina support. Under visible light irradiation, the reaction rate of HMF formation is ~143 times higher than the equivalent thermal reaction performed in the absence of light. The turnover number (TON) of the heterogeneous gallium(III) photocatalyst was as high as 1500, which was ca. two orders of magnitude higher than the TON of the homogeneous gallium(III) system. It is proposed that photoirradiation significantly enhances the Lewis acidity of the catalyst by forming a semi-coordination state between gallium(III) and N-donor ligands, enabling the increased interaction of reactant sugar molecules with gallium(III) active sites. Consistent with this, the photoresponsive coordination of the gallium(III) complex and the abstraction of the hydroxy group by the metal under irradiation with visible light is observed by NMR spectroscopy for the first time. These findings demonstrate that efficient photocatalysts derived from the main group elements can facilitate biomass conversion using visible light.

High‐Efficiency Solar Transformation of Sugars via a Heterogenous Gallium(III) Catalyst

AbstractExtremely limited research exploring the photocatalytic potential of main group metals, such as aluminum, gallium, and tin, has been undertaken due to their weak light harvesting properties. This study reports the efficient transformation of sugars to 5‐hydroxymethylfurfural (HMF) with high yield employing an original heterogeneous photocatalyst comprising a gallium(III) complex immobilized on an alumina support. Under visible light irradiation, the reaction rate of HMF formation is ~143 times higher than the equivalent thermal reaction performed in the absence of light. The turnover number (TON) of the heterogeneous gallium(III) photocatalyst was as high as 1500, which was ca. two orders of magnitude higher than the TON of the homogeneous gallium(III) system. It is proposed that photoirradiation significantly enhances the Lewis acidity of the catalyst by forming a semi‐coordination state between gallium(III) and N‐donor ligands, enabling the increased interaction of reactant sugar molecules with gallium(III) active sites. Consistent with this, the photoresponsive coordination of the gallium(III) complex and the abstraction of the hydroxy group by the metal under irradiation with visible light is observed by NMR spectroscopy for the first time. These findings demonstrate that efficient photocatalysts derived from the main group elements can facilitate biomass conversion using visible light.

Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In the clinical realm, platinum-based drugs hold an important role in the chemotherapy of CRC. Nonetheless, a multitude of patients, due to tumor protein 53 (TP53) gene mutations, experience the emergence of drug resistance. This phenomenon gravely impairs the effectiveness of therapy and long-term prognosis. Gallium, a metallic element akin to iron, has been reported that has the potential to be used to develop new metal anticancer drugs. In this study, we screened and established the gallium complex K6 as a potent antitumor agent in both in vitro and in vivo. K6 exhibited superior efficacy in impeding the growth, proliferation, and viability of CRC cells carrying TP53 mutations compared to oxaliplatin. Mechanistically, K6 escalated reactive oxygen species levels and led deoxyribonucleic acid (DNA) damage. Furthermore, K6 effectively suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase 3 beta (GSK3β) pathway, leading to the degradation of its downstream effectors myelocytomatosis (c-Myc) and Krueppel-like factor 5 (KLF5). Conversely, K6 diminished the protein expression of WW domain-containing protein 1 (WWP1) while activating phosphatase and tensin homolog (PTEN) through c-Myc degradation. This dual action further demonstrated the potential of K6 as a promising therapeutic compound for TP53-mutated CRC.

Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe’s interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.

Synthesis, Characterization, and Cytotoxicity of a Ga(III) Complex with Warfarin

The gallium(III) complex of warfarin was synthesized, and its structure was determined by means of theoretical, analytical, and spectral analyses. Significant differences in the IR and Raman spectra of the complex were observed as compared to the spectra of the ligand and confirmed the suggested metal-ligand binding mode. The theoretical study of the Ga(III) complex of warfarin has been done to elucidate the structure-activity relation, inter- and intra-molecular interactions, and frontier molecular orbital energy analysis based on DFT computations. A molecular docking study has been performed to predict the biological activity of the molecule. In this paper, we report preliminary results about the cytotoxicity of the investigated compounds. The cytotoxic effects of the ligand and its Ga(III) complex were determined using the MTT method on different tumor cell lines. The screening performed revealed that the tested compounds exerted cytotoxic activity on the evaluated cell lines.

Investigating the Effect of Cyclodextrin Nanosponges and Cyclodextrin-Based Hydrophilic Polymers on the Chemical Pharmaceutical and Toxicological Profile of Al(III) and Ga(III) Complexes with 5-Hydroxyflavone

In the present study, the complexes of aluminum and gallium with 5-hydroxyflavone were evaluated for their interaction with cyclodextrin polymers, as well as for the pharmacological effect of their inclusion. The cyclodextrin polymers were synthesized using diphenylcarbonate as a crosslinking agent, resulting in a lipophilic nanosponge (DPCNS), and pyromellitic dianhydride, resulting in a hydrophilic polymer (PMDACD). The inclusion complexes were synthesized and characterized via IR spectrometry and thermal analysis. The effect on the solubility of the metal complexes was also studied, where the hydrophobic nanosponge did not lead to an increase in solubility, but on the contrary, in the case of Al, it decreased; meanwhile, in the case of the hydrophilic polymer, the solubility of the metal complexes increased with the amount of polymer added. The cytostatic effect of inclusion complexes was investigated on two cell lines with different localizations, human colon adenocarcinoma (LoVo) and human ovarian adenocarcinoma (SKOV-3). The cytostatic efficacy is increased compared to simple complexes with efficacy on LoVo cells. Compared between the two metals, gallium complexes proved to be more active, with the efficacy of gallium complexes with the PMDACD being approximately the same as that of cisplatin, an antitumor agent used in therapy.

Dipyrromethene as a Ligand for the Stabilization of Low-Valent Gallium Complexes

Dipyrromethene as a Ligand for the Stabilization of Low-Valent Gallium Complexes

Gallium(III) complexes with 1,3-pdta-type of ligands: The influence of an alkyl substituent in 1,3-propanediamine chain and the metal counter cation on the structural properties of the complex

The hexadentate 1,3-propanediamine-N,N,N’,N’-tetraacetate (1,3-pdta4−) and (±)-1,3-pentanediamine-N,N,N’,N’-tetraacetate (1,3-pndta4−) ligands were used for the synthesis of two new gallium(III) complexes, Na[Ga(1,3-pdta)]·3H2O (1) and Ba[Ga(1,3-pndta)]2·3H2O (2). Complexes 1 and 2 were characterized by IR and NMR (1H and 13C) spectroscopy and single crystal X-ray diffraction analysis. The obtained results have shown that both hexadentate 1,3-pdta4− and 1,3-pndta4− ligands are coordinated to gallium(III) ion through the two nitrogen and four carboxylate oxygen atoms. Both complexes show significant octahedral distortion since the mean angular deviation is nearly four degrees per angle. However, the octahedral distortion of complex 2 is lower than of 1, as indicated by the ΣΔ(Oh) values (48° and 49° versus 53°, respectively). The binding interactions of the complexes 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were studied by fluorescence emission spectroscopy. Both complexes can bind to the serum albumin reversibly, while their affinity to ct-DNA is rather low.

Catalytic reactions with low-valency ambiphilic gallium complexes

Catalytic reactions with low-valency ambiphilic gallium complexes

Aluminum Tris(2-pyridyl)borates: Structure, reactivity and catalysis

Tris(2-pyridyl)borates are emerging scorpionate ligands distinguished by their robustness and modularity, as well as their strong electron-donicity. Metal tris(2-pyridyl)borates show a strong tendency toward six-coordinate, pseudooctahedral metal geometries with static κ3-ligation. Most exceptions involve sterically hindered tris(2-pyridyl)borates. We report four-coordinate alkylaluminum complexes with the sterically unhindered ligand phenyl tris(2-pyridyl)borate (Tpy–), using single-crystal XRD, variable-temperature NMR, and computational modelling to characterize their structure and dynamics. Thus proton exchange between TpyH and trialkylaluminum gave four-coordinate complexes TpyAlR2 (–R = methyl, ethyl, and isobutyl), the first κ2-complexes of sterically unhindered tris(2-pyridyl)borates. Moreover, pyridine coordination in TpyAlR2 complexes is fluxional, showing NMR symmetry down to −80 °C. Computational modelling suggests that pyridine exchange occurs through a higher energy five-coordinate κ3-conformation. By contrast, the analogous gallium complex TpyGaMe2 is also κ2, but NMR does not show pyridine interconversion even up to 70 °C. Alternatively, proton exchange involving TpyH, trialkylaluminums, and acids gives κ3, four-coordinate cations with the composition [TpyAlR]+ (–R = methyl, ethyl, and isobutyl), in addition to an unusual protonated tris(2-pyridyl)borate complex [TpyHAliBu2]+. Furthermore, reaction of TpyH with two equivalents of AlMe3 gave the first bimetallic tris(2-pyridyl)borate complex TpyAl2Me5, with distinct κ2- and κ1-bound aluminum sites. Finally, we characterize controlled polymerization of ε-caprolactone by these complexes at high temperatures.

Reversible O-H Bond Activation by Tripodal tris(Nitroxide) Aluminum and Gallium Complexes.

Herein, we report the preparation and characterization of the Group 13 metal complexes of a tripodal tris(nitroxide)-based ligand, designated (TriNOx3-)M (M = Al (1), Ga (2), In (3)). Complexes 1 and 2 both activate the O-H bond of a range of alcohols spanning a ∼10 pKa unit range via an element-ligand cooperative pathway to afford the zwitterionic complexes (HTriNOx2-)M-OR. Structures of these alcohol adduct products are discussed. We demonstrate that the thermodynamic and kinetic aspects of the reactions are both influenced by the identity of the metal, with 1 having higher reaction equilibrium constants and proceeding at a faster rate relative to 2 for any given alcohol. These parameters are also influenced by the pKa of the alcohol, with more acidic alcohols reacting both to more completion and faster than their less acidic counterparts. Possible mechanistic pathways for the O-H activation are discussed.

New Stable Gallium(III) and Indium(III) Complexes with Thiosemicarbazone Ligands: A Biological Evaluation.

The aim of this work is to explore a new library of coordination compounds for medicinal applications. Gallium is known for its various applications in this field. Presently, indium is not particularly important in medicine, but it shares a lot of chemical traits with its above-mentioned lighter companion, gallium, and is also used in radio imaging. These metals are combined with thiosemicarbazones, ligating compounds increasingly known for their biological and pharmaceutical applications. In particular, the few ligands chosen to interact with these hard metal ions share the ideal affinity for a high charge density. Therefore, in this work we describe the synthesis and the characterization of the resulting coordination compounds. The yields of the reactions vary from a minimum of 21% to a maximum of 82%, using a fast and easy procedure. Nuclear Magnetic Resonance (NMR) and Infra Red (IR) spectroscopy, mass spectrometry, elemental analysis, and X-ray Diffraction (XRD) confirm the formation of stable compounds in all cases and a ligand-to-metal 2:1 stoichiometry with both cations. In addition, we further investigated their chemical and biological characteristics, via UV-visible titrations, stability tests, and cytotoxicity and antibiotic assays. The results confirm a strong stability in all explored conditions, which suggests that these compounds are more suitable for radio imaging applications rather than for antitumoral or antimicrobic ones.

Effects of a central element on the photoluminescence properties of β-diketiminate complexes composed of group 13 elements.

Various kinds of boron complexes have been utilized as functional luminescent materials. However, only a limited number of emissive complexes containing other group 13 elements have been reported. Herein, we report the synthesis and optical properties of luminescent β-diketiminate complexes containing a series of group 13 elements. The synthesized complexes exhibited crystallization-induced emission properties. It was indicated that the heavier group 13 elements accelerate intersystem crossing from the singlet to the triplet excited state because of the strong heavy atom effect. Finally, we discovered that aluminum and gallium complexes can work as solid-state luminescent materials with high emission efficiencies.

Highly selective organo-gallium hydroxamate mediated inhibition of antibiotic resistant Klebsiella pneumoniae

Five complexes of gallium derived from hydroxamic acids have been synthesised, characterised, and their anti-bacterial activity and mammalian cell toxicity established. These are three metal-organic complexes; [Ga(BPHA]3 1, [Ga(BHA-H]3 2,...

Utilisation of a dianionic pentadentate ligand in group 13 chemistry

Using the pentadentate tetrapyrazolylpyridyl diborate (B2Pz4Py) ligand allowed for the isolation of overall seven group 13 complexes, which have been fully characterised and whose solid-state structures were obtained by single-crystal X-ray diffraction analysis. The aluminium chloride (1) and bromide (2) complexes as well as the gallium chloride (3) and iodide (4) complexes are accessible by deprotonation of the ligand precursors [B2Pz4LiPyH]2 with lithium hexamethyldisilazide and subsequent reaction with aluminium and gallium trihalides. Using indium(I) chloride instead gives rise to the indium(III) bis(trimethylsily)amide complex 5. Chloride abstraction from the aluminium(III) complex 1 using a combination of TlBArF24 and TlPF6 affords the related aluminium(III) fluoride complex 6 while using the gallium(III) complex 3 yields the dinuclear cationic PF2O2-bridged gallium(III) complex 7.

Azide-modified corrole phosphorus complexes for endoplasmic reticulum-targeted fluorescence bioimaging and effective cancer photodynamic therapy

Study on corrole photosensitizers (PSs) for photodynamic therapy (PDT) has made remarkable progress. Targeted delivery of PSs is of great significance for enhancing therapeutic efficiency, decreasing the dosage, and reducing systemic toxicity during PDT. The development of PSs that can be specifically delivered to the subcellular organelle is still an attractive and challenging work. Herein, we synthesize a series of azide-modified corrole phosphorus and gallium complex PSs, in which phosphorus corrole 2-P could not only precisely target the endoplasmic reticulum (ER) with a Pearson correlation coefficient (PCC) up to 0.92 but also possesses the highest singlet oxygen quantum yields (ΦΔ = 0.75). This renders it remarkable PDT activity at a very low dosage (IC50 = 23 nM) towards HepG2 tumor cell line while ablating solid tumors in vivo with excellent biosecurity. Furthermore, 2-P exhibits intense red fluorescence (ΦF = 0.25), outstanding photostability, and a large Stokes shift (190 nm), making it a promising fluorescent probe for ER. This study provides a clinically potential photosensitizer for cancer photodynamic therapy and a promising ER fluorescent probe for bioimaging.

Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections.