Fe3+-activated magnetoplumbite persistent luminescence phosphor by modulating the oxygen vacancy.

Broadband near-infrared (NIR) spectroscopy has gained significant attention due to its versatile application in various fields. In the realm of NIR phosphors, Fe3+ ion is an excellent activator known for its nontoxic and harmless nature. In this study, we prepared an Fe3+-activated SrGa12O19 (SGO) NIR phosphor and analyzed its phase and luminescence properties. Upon excitation at 326 nm, the SGO:Fe3+ phosphor exhibited a broadband emission in the range 700-1000 nm, peaking at 816 nm. The optical band gap of SGO:Fe3+ was evaluated. To enhance the long-lasting phosphorescence, an oxygen vacancy-rich SGO:Fe3+ (VO-SGO:Fe3+) sample was prepared for activation. Interestingly, the increase in the oxygen-vacancy concentration indeed contributed to the activation of persistent luminescence of Fe3+ ions. The VO-SGO:Fe3+ sample has a long duration and high charge storage capacity, allowing it to perform efficiently in various applications. This work provides the foundation for further design of Cr3+-free PersL phosphors with efficient NIR PersL.

A comparative study of two thienopyrimidine Schiff base probes for sequential monitoring of Ga3+ and Pd2.

Two Schiff base probes (S1 and S2) were prepared and synthesized by incorporating thienopyrimidine into salicylaldehyde or 3-ethoxysalicylaldehyde individually, with the aim of detecting Ga3+ and Pd2+ sequentially. Upon chelation with Ga3+, S1 and S2 exhibited fluorescence enhancement in DMSO/H2O buffer. Both S1-Ga3+ and S2-Ga3+ were quenched by Pd2+. The limit of detection for S1 in response to Ga3+ and Pd2+ was 2.86 × 10-7 and 4.4 × 10-9 M, respectively. For S2, the limit of detection for Ga3+ and Pd2+ was 4.15 × 10-8 and 3.0 × 10-9 M, respectively. Furthermore, the complexation ratios of both S1 and S2 with Ga3+ and Pd2+ were determined to be 1:2 through Job's plots, ESI-MS analysis, and theoretical calculations. Two molecular logic gates were constructed, leveraging the response behaviors of S1 and S2. Moreover, the potential utility of S1 and S2 for monitoring Ga3+ and Pd2+ in domestic water was verified.

Reservoir Computing Based on Oxygen-Vacancy-Mediated X-ray Optical Synaptic Device for Medical CT Bone Diagnosis.

Recognition and judgment of X-ray computed tomography (CT) images play a crucial role in medical diagnosis and disease prevention. However, the storage and calculation of the X-ray imaging system applied in the traditional CT diagnosis is separate, and the pathological judgment is based on doctors' experience, which will affect the timeliness and accuracy of decision-making. In this paper, a simple-structured reservoir computing network (RC) is proposed based on Ga2O3 X-ray optical synaptic devices to recognize medical skeletal CT images with high accuracy. Through oxygen vacancy engineering, Ga2O3 X-ray optical synaptic devices with adjustable photocurrent gain and a persistent photoconductivity effect were obtained. By using the Ga2O3 X-ray optical synaptic device as a reservoir, we constructed an RC network for medical skeletal CT diagnosis and verified its image recognition capability using the MNIST data set with an accuracy of 78.08%. In the elbow skeletal CT image recognition task, the recognition rate is as high as 100%. This work constructs a simple-structured RC network for X-ray image recognition, which is of great significance in applications in medical fields.

Extended-Gate FET Biosensor Based on GaN Micropillar Array and Polycrystalline Layer: Application to Hg2+ Detection in Human Urine.

Owing to the separation of field-effect transistor (FET) devices from sensing environments, extended-gate FET (EGFET) biosensor features high stability and low cost. Herein, a highly sensitive EGFET biosensor based on a GaN micropillar array and polycrystalline layer (GMP) was fabricated, which was prepared by using simple one-step low-temperature MOCVD growth. In order to improve the sensitivity and detection limit of EGFET biosensor, the surface area and the electrical conductivity of extended-gate electrode can be increased by the micropillar array and the polycrystalline layer, respectively. The designed GMP-EGFET biosensor was modified with l-cysteine and applied for Hg2+ detection with a low limit of detection (LOD) of 1 ng/L, a high sensitivity of -16.3 mV/lg(µg/L) and a wide linear range (1 ng/L-24.5 µg/L). In addition, the detection of Hg2+ in human urine was realized with an LOD of 10 ng/L, which was more than 30 times lower than that of reported sensors. To our knowledge, it is the first time that GMP was used as extended-gate of EGFET biosensor.

Electrochemical platform for detecting Escherichia coli bacteria using machine learning methods.

We present an electrochemical platform designed to reduce time of Escherichia coli bacteria detection from 24 to 48-h to 30 min. The presented approach is based on a system which includes gallium-indium (eGaIn) alloy to provide conductivity and a hydrogel system to preserve bacteria and their metabolic species during the analysis. The work is dedicated to accurate and fast detection of Escherichia coli bacteria in different environments with the supply of machine learning methods. Electrochemical data obtained during the analysis is processed via multilayer perceptron model to identify i.e. predict bacterial concentration in the samples. The performed approach provides the effectiveness of bacteria identification in the range of 102-109 colony forming units per ml with the average accuracy of 97%. The proposed bioelectrochemical system combined with machine learning model is prospective for food analysis, agriculture, biomedicine.

Phase transition-driven encapsulation of biomolecules using liquid metal with on-demand release for biomedical applications.

Robust encapsulation and controllable release of biomolecules have wide biomedical applications ranging from biosensing, drug delivery to information storage. However, conventional biomolecule encapsulation strategies have limitations in complicated operations, optical instability, and difficulty in decapsulation. Here, we report a simple, robust, and solvent-free biomolecule encapsulation strategy based on gallium liquid metal featuring low-temperature phase transition, self-healing, high hermetic sealing, and intrinsic resistance to optical damage. We sandwiched the biomolecules with the solid gallium films followed by low-temperature welding of the films for direct sealing. The gallium can not only protect DNA and enzymes from various physical and chemical damages but also allow the on-demand release of biomolecules by applying vibration to break the liquid gallium. We demonstrated that a DNA-coded image file can be recovered with up to 99.9% sequence retention after an accelerated aging test. We also showed the practical applications of the controllable release of bioreagents in a one-pot RPA-CRISPR/Cas12a reaction for SARS-COV-2 screening with a low detection limit of 10 copies within 40 min. This work may facilitate the development of robust and stimuli-responsive biomolecule capsules by using low-melting metals for biotechnology.

In Silico Analysis of the Ga3+/Fe3+ Competition for Binding the Iron-Scavenging Siderophores of P. aeruginosa-Implementation of Three Gallium-Based Complexes in the "Trojan Horse" Antibacterial Strategy.

The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe2+/3+-containing enzymes have been identified as a plausible target of great potential. The intriguing "Trojan horse" approach deprives microorganisms from the essential iron. Recently, gallium's potential in medicine as an iron mimicry species has attracted vast attention. Different Ga3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa. Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO3)3, metabolized to Ga3+-hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream-the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga3+/Fe3+ rivalry for binding the two bacterial siderophores.

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination.

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Gallium and silver-doped titanium surfaces provide enhanced osteogenesis, reduce bone resorption and prevent bacterial infection in co-culture.

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro. Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI. STATEMENT OF SIGNIFICANCE: This article provides important insights into titanium for fractures caused by osteoporosis or bone metastases with high incidence in surgical site infection (SSI) because in this situation bacterial infection can become a major disaster. In order to solve this unmet medical need, we propose a titanium implant modified with gallium and silver to improve osteointegration, reduce bone resorption and avoid bacterial infection. For that aim, we study osteoblast and osteoclast behavior with the main novelty focused on the antibacterial evaluation. In this work, we recreate "the race for the surface" in long-term experiments and study bacterial virulence factors (quorum sensing). Therefore, we believe that our article could be of great interest, providing a great impact on future orthopedic applications.

Recent advances and progress on the design, fabrication and biomedical applications of Gallium liquid metals-based functional materials.

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

Multi-project wafers for flexible thin-film electronics by independent foundries.

Flexible and large-area electronics rely on thin-film transistors (TFTs) to make displays1-3, large-area image sensors4-6, microprocessors7-11, wearable healthcare patches12-15, digital microfluidics16,17 and more. Although silicon-based complementary metal-oxide-semiconductor (CMOS) chips are manufactured using several dies on a single wafer and the multi-project wafer concept enables the aggregation of various CMOS chip designs within the same die, TFT fabrication is currently lacking a fully verified, universal design approach. This increases the cost and complexity of manufacturing TFT-based flexible electronics, slowing down their integration into more mature applications and limiting the design complexity achievable by foundries. Here we show a stable and high-yield TFT platform for the fabless manufacturing of two mainstream TFT technologies, wafer-based amorphous indium-gallium-zinc oxide and panel-based low-temperature polycrystalline silicon, two key TFT technologies applicable to flexible substrates. We have designed the iconic 6502 microprocessor in both technologies as a use case to demonstrate and expand the multi-project wafer approach. Enabling the foundry model for TFTs, as an analogy of silicon CMOS technologies, can accelerate the growth and development of applications and technologies based on these devices.

Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 µM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.

Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10-22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.

Thinner is not always better: Optimizing cryo-lamellae for subtomogram averaging.

Cryo-electron tomography (cryo-ET) is a powerful method to elucidate subcellular architecture and to structurally analyze biomolecules in situ by subtomogram averaging, yet data quality critically depends on specimen thickness. Cells that are too thick for transmission imaging can be thinned into lamellae by cryo-focused ion beam (cryo-FIB) milling. Despite being a crucial parameter directly affecting attainable resolution, optimal lamella thickness has not been systematically investigated nor the extent of structural damage caused by gallium ions used for FIB milling. We thus systematically determined how resolution is affected by these parameters. We find that ion-induced damage does not affect regions more than 30 nanometers from either lamella surface and that up to ~180-nanometer lamella thickness does not negatively affect resolution. This shows that there is no need to generate very thin lamellae and lamella thickness can be chosen such that it captures cellular features of interest, thereby opening cryo-ET also for studies of large complexes.

Fabrication of 3D-printed scaffolds loaded with gallium acetylacetonate for potential application in osteoclastic bone resorption.

We recently reported the potential of a new gallium compound, gallium acetylacetonate (GaAcAc) in combating osteoclastic bone resorption through inhibition of osteoclast differentiation and function. Herein, we focused on 3D-printed polylactic acid scaffolds that were loaded with GaAcAc and investigated the impact of scaffold pretreatment with polydopamine (PDA) or sodium hydroxide (NaOH). We observed a remarkable increase in scaffold hydrophilicity with PDA or NaOH pretreatment while biocompatibility and in vitro degradation were not affected. NaOH-pretreated scaffolds showed the highest amount of GaAcAc loading when compared to other scaffolds (p < 0.05). NaOH-pretreated scaffolds with GaAcAc loading showed effective reduction of osteoclast counts and size. The trend was supported by suppression of key osteoclast differentiation markers such as NFAT2, c-Fos, TRAF6, & TRAP. All GaAcAc-loaded scaffolds, regardless of surface pretreatment, were effective in inhibiting osteoclast function as evidenced by reduction in the number of resorptive pits in bovine cortical bone slices (p < 0.01). The suppression of osteoclast function according to the type of scaffold followed the ranking: GaAcAc loading without surface pretreatment > GaAcAc loading with NaOH pretreatment > GaAcAc loading with PDA pretreatment. Additional studies will be needed to fully elucidate the impact of surface pretreatment on the efficacy and safety of GaAcAc-loaded 3D-printed scaffolds.

Synthesis, characterization and in vitro cytotoxicity of gallium(III)-dithiocarbamate complexes.

A library of homoleptic mononuclear Ga(III) complexes of the general formula [Ga(DTC)3], where DTC is an alicyclic or a linear dithiocarbamate chelator, is reported. The complexes were prepared in high yields starting from Ga(NO3)3·6H2O and fully characterized by elemental analysis and IR and NMR spectroscopy. Crystals of five of these complexes were obtained. The antitumor activity of the newly synthesized compounds against a panel of human cancer cell lines was evaluated. The chemical nature of the DTC does not have a marked impact on the structural features of the final compound. X-ray crystal structure analyses revealed that all these complexes have a trigonal prismatic geometry with three identical chelating DTCs coordinating the Ga(III) ion. It is noteworthy that in complex 22, [Ga(NHEt)3] (NHEt = N-ethyldithiocarbamate), the asymmetric unit is formed by two independent and structurally different molecules. Cellular studies showed that all the synthesized Ga-DTC complexes exhibit marked cytotoxic activity, even against human colon cancer cells that are less sensitive to cisplatin. Among the tested compounds, 6 ([Ga(CEPipDTC)3], CEPipDTC = (ethoxycarbonyl)-piperidinedithiocarbamate) and 21 ([Ga(Pr-13)3], PR13 = 4 and N-(2-ethoxy-2-oxoethyl)-N-methyldithiocarbamate) are very promising derivatives, but they have no selectivity towards cancer cells. Nevertheless, the obtained data provide a foundation for developing gallium-dithiocarbamate complexes as anticancer agents.

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.

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.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

Structure-activity effects in the anti-leishmanial activity of di-alkyl gallium quinolin-8-olates.

Six (G1-G6) novel organogallium complexes of the general formula [Ga(R)2quin] (where R = Et, iPr, nBu, tBu, sBu and hexyl; quin = quinolin-8-olate, C9H6NO) have been synthesised and fully characterised. Single crystal X-ray diffraction shows the complexes adopt a five-coordinate geometry through dimerisation. Complexes G1-G5 were analytically pure and could undergo further biological analysis. [Ga(hex)2quin] G6 could not be satisfactorily purified and was excluded from biological assays. 1H NMR spectroscopy indicated the complexes are stable to hydrolysis over 24 hours in 'wet' d6-DMSO. Complexes G1-G5 were assessed for their anti-leishmanial activity towards three separate strains: L. major, L. amazonensis and L. donovani, with varied results toward the promastigote form. G1 and G2 were found to be the most selective with little to no toxicity towards mammalian cell lines. Amastigote invasion assays on the three strains showed that [Ga(nBu)2quin] G3 and [Ga(tBu)2quin] G4 gave the best all round anti-parasitic activity with percentage infection ranges of 1.50-3.00% and 3.25-7.50% respectively, with G3 out-performing the drug control amphotericin B in all three assays. The activity was found to correlate with lipophilicity and water solubility, with the most effective G3 proving the most lipophilic and least water soluble.