Role Of Citrate Research Articles

Histidinehydroxamic acid as new biomolecule to produce molecular-like fluorescent gold nanoclusters: Possible mechanisms for metal ion sensing

We firstly demonstrate a new biomolecule, Histidinehydroxamic acid (HisHA), to produce few-atomic fluorescent gold nanoclusters (Au NCs) in aqueous medium. The preparation protocol has been optimized by studying the effect of metal ion/biomolecule molar ratio, metal ion concentration, pH, temperature, reaction time as well as the role of citrate as mild reducing agent on appearance of blue-emitting (λem = 440 nm, λex = 365 nm) molecular-like NCs. Structural studies confirmed that imidazole-N and amino-N of the HisHA stabilize the formed metallic cores. The quantum yield of ∼ 4% and fluorescence lifetime of 4.2 ns were determined. Moreover, these NCs show suitable stability under high inert salt (cNaCl = 2.5 M) concentration as well. Verifying its ability to detect metal ions, dual strategies were discovered. We confirmed that the copper ions cause fluorescence quenching (LOD = 2.49 µM) by pushing the higher amount of soft HisHA ligand from the metallic surface and forming complexes with dominantly hydroxamate-[O,O] coordination mode in the aqueous medium. For Zn2+-ions, a “turn-on” sensing mechanism was observed; the smallest detectable amount of Zn2+ is 7.5 µM. Linear increase of the quantum yield (from ∼ 4% to ∼ 11.5%) was identified above 75 μM of Zn2+ due to the binding of the Zn2+-ions on the cluster surface via hydroxamate-[O,O] donors.

Role of Trisodium Citrate and Nanominerals in Mastitis Management in Dairy Animals: A Review

Mastitis is the most common disease of dairy cattle across the globe including India and cause huge economic losses to dairy farmers. Mastitis is also the most common reason for antibiotic usage in dairy animals, which is an important reason for antimicrobial resistance development in human and veterinary important pathogen. Optimization of nutrition and improvement of immunity of lactating cows are important strategies to reduce the susceptibility to mastitis and thereby reduction of antibiotic use. Copper, Zinc and Manganese are important trace minerals for maintaining udder health and immunity but, their contents and bioavailability is affected by several factors. Citrate, the precursor for milk synthesis is an important determinant of udder health but, the role of citrate in udder health is not clear as milk citrate level is affected by various factors. This review discusses about the role of trisodium citrate and various forms of trace minerals in mastitis management in dairy animals.

The role of citrate in heterogeneous silver metal catalyst formation: A mechanistic consideration

The formation of silver particles as initial catalyst for the electroless copper deposition is an essential part of the formation of conductive structures in flexible electronics. In this work, we have investigated the basic mechanism using the citrate anion for the fixation of silver species and later metal catalyst formation directly on a textile substrates surface. During the particle formation process and the subsequent electroless copper deposition, silver changes its oxidation state several times. While the decomposition of bulk silver citrate leads to silver metal, the distribution on the substrate surface leads to silver oxide due to the oxidation under air. Finally, the reducing conditions in the copper deposition step, i.e. alkaline formaldehyde, convert any silver-ion to silver metal. In parallel, the thermal decomposition of silver citrate also forms CO2 and hexane-2,5-dione. The latter is the result of an auto oxidation reaction similar to Kolbe electrolysis, i.e. symmetrical radical recombination of two acetonyl radicals remaining from the decarboxylated citrate scaffold.

Citrate does not change viscoelastic haemostatic assays after cardiopulmonary bypass.

Viscoelastic hemostatic assays (VHA) are commonly used to identify specific cellular and humoral causes for bleeding in cardiac surgery patients. Cardiopulmonary bypass (CPB) alterations to coagulation are observable on VHA. Citrated VHA can approximate fresh whole blood VHA when kaolin is used as the activator in healthy volunteers. Some have suggested that noncitrated blood is more optimal than citrated blood for point-of-care analysis in some populations. To determine if storage of blood samples in citrate after CPB alters kaolin activated VHA results. This was a prospective observational cohort study at a single tertiary care teaching hospital. Blood samples were subjected to VHA immediately after collection and compared to samples drawn at the same time and stored in citrate for 30, 90, and 150 min prior to kaolin activated VHA both before and after CPB. VHA results were compared using paired T-tests and Bland-Altman analysis. Maximum clot strength and time to clot initiation were not considerably different before or after CPB using paired T-tests or Bland-Altman Analysis. Citrated samples appear to be a clinically reliable substitute for fresh samples for maximum clot strength and time to VHA clot initiation after CPB. Concerns about the role of citrate in altering the validity of the VHA samples in the cardiac surgery population seem unfounded.

Single-Crystal Electrochemistry Uncovers the Role of Citrate in the Anisotropic Growth of Ag Nanostructures

Shape-controlled synthesis of metal nanocrystals is usually achieved by the addition of capping agents and serves an important approach to endowing metal nanomaterials with desired properties.1 A widely accepted hypothesis in the role of capping agents is they suppress the atomic deposition on the facets they selectively adsorb to, which leads to anisotropic growth.2 However, the roles of capping agents are often qualitatively deduced from the shape of metal nanocrystals formed, making it difficult to rationally design a synthetic condition for a certain shape or aspect ratio. Single-crystal electrochemical measurements have been used to uncover the facet-selective roles of a wide range of capping agents, such as chloride in the synthesis of Cu nanowires, bromide in the synthesis of Au nanorods, and iodide in the synthesis of Cu microplates.3-6 However, the anisotropic growth revealed by the growth of these nanocrystals is 10 times higher than that predicted by the single-crystal electrochemical measurements, indicating planar defects, such as twin planes and stacking faults, can also cause anisotropic growth.To elucidate the effects surface capping and defects in the anisotropic growth of metal nanocrystals, the work presented here combines synthetic methods and electrochemical measurements to reveal the roles of citrate in the growth of seeds with different structures.7 The single-crystal Ag seeds (Figure 1A) grow into cuboctahedra in the absence of citrate (Figure 1B) and octahedra in the presence of citrate (Figure 1C), which closely matches the shape prediction from the electrochemical measurements. Linear sweep voltammetry (LSV) measurements under the synthetic conditions demonstrate the anisotropic growth with citrate is a result of citrate selectively suppressing the oxidation of a reducing agent, ascorbic acid, and citrate does not affect silver ion reduction. The Ag nanoplate seeds with planar defects (Figure 1D) undergo isotropic growth in the absence of citrate (Figure 1E), but exhibit 30~100 times more anisotropic growth in the presence of citrate than the single-crystal seeds and electrochemical prediction (Figure 1F). Further investigation suggests planar defects can catalyze silver atom deposition to the nanoplate side planes and citrate suppresses surface diffusion to the nanoplate basal planes.(1) Yang, T.-H.; Shi, Y.; Janssen, A.; Xia, Y., Surface Capping Agents and Their Roles in Shape-Controlled Synthesis of Colloidal Metal Nanocrystals. Angew. Chem., Int. Ed. 2020, 59, 15378-15401.(2) Xia, Y.; Xiong, Y.; Lim, B.; Skrabalak, S. E., Shape-Controlled Synthesis of Metal Nanocrystals: Simple Chemistry Meets Complex Physics? Angew. Chem., Int. Ed. 2009, 48, 60-103.(3) Kim, M. J.; Brown, M.; Wiley, B. J., Electrochemical investigations of metal nanostructure growth with single crystals. Nanoscale 2019, 11, 21709-21723.(4) Kim, M. J.; Alvarez, S.; Chen, Z.; Fichthorn, K. A.; Wiley, B. J., Single-Crystal Electrochemistry Reveals Why Metal Nanowires Grow. J. Am. Chem. Soc. 2018, 140, 14740-14746.(5) Brown, M.; Wiley, B. J., Bromide Causes Facet-Selective Atomic Addition in Gold Nanorod Syntheses. Chem. Mater. 2020, 32, 6410-6415.(6) Kim, M. J.; Cruz, M. A.; Chen, Z.; Xu, H.; Brown, M.; Fichthorn, K. A.; Wiley, B. J., Isotropic Iodide Adsorption Causes Anisotropic Growth of Copper Microplates. Chem. Mater. 2021, 33, 881-891.(7) Xu, H.; Wiley, B. J., The Roles of Citrate and Defects in the Anisotropic Growth of Ag Nanostructures. Chem. Mater. 2021, 33, 8301-8311. Figure 1

Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease.

Recent mouse model experiments support an instrumental role for senescent cells in age-related diseases and senescent cells may be causal to certain age-related pathologies. A strongly supported hypothesis is that extranuclear chromatin is recognized by the cyclic GMP–AMP synthase-stimulator of interferon genes pathway, which in turn leads to the induction of several inflammatory cytokines as part of the senescence-associated secretory phenotype. This sterile inflammation increases with chronological age and age-associated disease. More recently, several intracellular and extracellular metabolic changes have been described in senescent cells but it is not clear whether any of them have functional significance. In this review, we highlight the potential effect of dietary and age-related metabolites in the modulation of the senescent phenotype in addition to discussing how experimental conditions may influence senescent cell metabolism, especially that of energy regulation. Finally, as extracellular citrate accumulates following certain types of senescence, we focus on the recently reported role of extracellular citrate in aging and age-related pathologies. We propose that citrate may be an active component of the senescence-associated secretory phenotype and via its intake through the diet may even contribute to the cause of age-related disease.

On the role of citrate in 12-molybdophosphoric-acid methods for quantification of phosphate in the presence of ATP

Citrate is a useful additive for measuring ATPase activities avoiding the interference of phosphate release after catalysis. In this work we explore this effect, and optimize the malachite green procedure for determination of phosphate.

Extracellular citrate serves as a DAMP to activate macrophages and promote LPS-induced lung injury in mice

Citrate has a prominent role as a substrate in cellular energy metabolism. Recently, citrate has been shown to drive inflammation. However, the role of citrate in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains unclear. Here, we aimed to clarify whether extracellular citrate aggravated the LPS-induced ALI and the potential mechanism. Our findings demonstrated that extracellular citrate aggravated the pathological lung injury induced by LPS in mice, characterized by up-regulation of pro-inflammatory factors and over-activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in the lungs. In vitro, we found that citrate treatment significantly augmented the expression of NLRP3 and pro-IL-1β and enhanced the translocation of NF-κB/p65 into the nucleus. Furthermore, extracellular citrate plus adenosine-triphosphate (ATP) significantly increased the production of reactive oxygen species (ROS) in primary murine macrophages. Inhibiting the production of ROS with a ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the activation of NLRP3 inflammasome. Altogether, we conclude that extracellular citrate may serve as a damage-associated molecular pattern (DAMP) and aggravates LPS-induced ALI by activating the NLRP3 inflammasome.

The Roles of Citrate and Defects in the Anisotropic Growth of Ag Nanostructures

The Roles of Citrate and Defects in the Anisotropic Growth of Ag Nanostructures

Citrate Stabilizes Hydroxylapatite Precursors: Implications for Bone Mineralization.

Mineralization of hydroxylapatite (HAp), the main inorganic phase in bone, follows nonclassical crystallization routes involving metastable precursors and is strongly influenced by organic macromolecules. However, the effect of small organic molecules such as citrate on the formation of HAp is not well constrained. Using potentiometric titration experiments and titration calorimetry, in combination with a multianalytical approach, we show that citrate stabilizes prenucleation species as well as a liquid-like calcium phosphate precursor formed before any solid phase nucleates in the system. The stabilization of a liquid-like precursor phase could facilitate infiltration into the cavities of the collagen fibrils during bone mineralization, explaining the enhancement of collagen-mediated mineralization by citrate reported in previous studies. Hence, citrate can influence bone mineralization way before any solid phase (amorphous or crystalline) is formed. We also show that HAp formation after amorphous calcium phosphate (ACP) in the absence and presence of citrate results in nanoplates of about 5–12 nm thick, elongated along the c axis. Such nanoplates are made up of HAp nanocrystallites with a preferred c axis orientation and with interspersed ACP. The nanoplatelet morphology, size, and preferred crystallographic orientation, remarkably similar to those of bone HAp nanocrystals, appear to be an intrinsic feature of HAp formed from an amorphous precursor. Our results challenge current models for HAp mineralization in bone and the role of citrate, offering new clues to help answer the long-standing question as to why natural evolution favored HAp as the mineral phase in bone.

Solvent‐Promoted Oxidation of Aromatic Alcohols/Aldehydes to Carboxylic Acids by a Laccase‐TEMPO System: Efficient Access to 2,5‐Furandicarboxylic Acid and 5‐Methyl‐2‐Pyrazinecarboxylic Acid

AbstractLaccase coupled with 2,2,6,6‐tetramethylpiperidinyl‐1‐oxy (TEMPO) is a well‐known catalytic system for the oxidation of alcohols to the carbonyl compounds. In this work, a simple yet effective solvent engineering strategy is developed to enable aromatic alcohols/aldehydes to be efficiently oxidized to carboxylic acids by a laccase‐TEMPO system. Citrate buffer (100–300 mm, pH 6) rather than the widely used acetate buffer (pH 4–5) proves to be optimal for this purpose. The roles of citrate are discussed in laccase‐TEMPO‐catalyzed synthesis of carboxylic acids. 5‐Hydroxymethylfurfural (HMF) of 200 mm is oxidized to 2,5‐furandicarboxylic acid (FDCA), a top‐value biobased chemical in the polymer industry, in 28 h with a yield of up to 97%. Of the 18 substrates examined, 11 alcohols are converted to target carboxylic acids with >90% yields by this method, with 2 alcohols giving >60% yields of carboxylic acids. Gram‐scale preparation of FDCA and 5‐methyl‐2‐pyrazinecarboxylic acid, an important drug intermediate, is demonstrated with total turnover numbers up to 110 000 for laccase and space‐time yields up to 1.0 g/(L•h). This chemoenzymatic approach may be a promising alternative to traditional chemical oxidations for the synthesis of carboxylic acids.

The effect of chemical structure of carboxylate molecules on hydroxyapatite nanoparticles. A structural and morphological study

Being the most abundant non-macromolecular organic component of bone, the role of citrate (Cit) in hydroxyapatite (HA) crystallization is of high relevance. In this work we have investigated the influence of hydroxycitrate (CitOH) and glutarate (Glr) on HA crystallization in terms of particle growth, composition, and morphology in comparison to Cit. CitOH and Glr have been selected for this work because they share the same backbone structure of Cit but bear different functional groups in the central region. Our data has revealed that CitOH strongly inhibits HA crystallization more efficiently than Cit. CitOH-HA nanoparticles are composed of platy, elongated particles similar to those of Cit-HA but they are ca. twice smaller and have a lower crystal order. On the other hand, Glr does not inhibit HA crystallization as Cit, but leads to the formation of OCP platelets that convert with maturation time to HA nanorods with larger aspect ratio than Cit-HA. In comparison to Cit-HA samples, Glr-HA nanoparticles have bigger dimensions, and higher structural order. Overall, our data reveal that the central carboxyl group of Cit is involved in the selective binding with HA crystal surface and in regulating HA crystal growth. The results of this work highlight new possibilities to control the formation of HA for designing advanced bioactive materials and give new insights on the role of the structure of Cit in regulating the HA morphology.

Role of Citrate in Pathophysiology and Medical Management of Bone Diseases.

Citrate is an intermediate in the “Tricarboxylic Acid Cycle” and is used by all aerobic organisms to produce usable chemical energy. It is a derivative of citric acid, a weak organic acid which can be introduced with diet since it naturally exists in a variety of fruits and vegetables, and can be consumed as a dietary supplement. The close association between this compound and bone was pointed out for the first time by Dickens in 1941, who showed that approximately 90% of the citrate bulk of the human body resides in mineralised tissues. Since then, the number of published articles has increased exponentially, and considerable progress in understanding how citrate is involved in bone metabolism has been made. This review summarises current knowledge regarding the role of citrate in the pathophysiology and medical management of bone disorders.

Nutritional requirements for Lactobacillus vini growth in sugarcane derivative substrate of ethanol fermentation.

Lactobacillus vini is a bacterial contaminant found in industrial environments of winemaking and fuel-ethanol fermentation. However, there has been no standard analysis of its physiology that can pinpoint its adaptive traits to these kinds of environments. In view of this lack of information, the aim of this study is to determine the nutritional factors that lead to the growth of L. vini in the industrial plants of fuel-ethanol. First of all, the limited growth of this bacterium was studied in the industrial substrate, which was improved by nutritional supplementation with amino acids, and its homofermentative status was confirmed. Metabolite analysis showed that citrate is a growth factor of paramount importance for this bacterium in industrial processes through pyruvate metabolization, and increases ATP production and biomass formation. Furthermore,e acetate uptake, either from the medium or generated from citrate metabolism, was assimilated for biomass production. Hence, a metabolic model was designed to describe the role of citrate and acetate in the growth of L. vini that could be tested on other lactobacilli.

A Mechanistic Understanding of Polysorbate 80 Oxidation in Histidine and Citrate Buffer Systems-Part 2.

In our previously published work, we reported rapid polysorbate 80 (PS80) oxidation in a histidine buffer after brief exposure to stainless steel and the ability of citrate and EDTA to prevent this oxidation. The focus of our current study was to mechanistically understand PS80 oxidation by studying the impacts of temperature, light, and stainless steel and the role of citrate and EDTA. Additionally, PS80 oxidation was studied in three different buffer systems: histidine, citrate, and phosphate. When the PS80-containing buffers in glass containers were exposed to the elevated temperature of 50°C, no PS80 oxidation was observed in either the histidine or the citrate buffer systems after 30 days; however, PS80 oxidation was observed in the phosphate buffer system within 14 days. These results demonstrated that temperature does not initiate PS80 oxidation in the histidine or the citrate buffer systems, but it may be a factor in the phosphate buffer system. When the three buffer systems containing PS80 were exposed to 20%, 50%, or 100% ICH Q1B light conditions and subsequently incubated in the dark at 50°C, the PS80 in the phosphate buffer system underwent oxidation within 7 days, whereas the PS80 in the histidine and the citrate buffer systems showed oxidation products only after 14 and 35 days, respectively. PS80 in the phosphate buffer system seemed to be the most vulnerable to light as PS80 in both the histidine and the citrate buffer systems underwent oxidation to a lesser extent, with faster oxidation occurring in the histidine buffer system than in the citrate buffer system. Finally, the ability of citrate and EDTA to act as not only chelators but also radical quenchers/scavengers was demonstrated when a metal ion, Fe2+, was spiked into the histidine buffer containing PS80. While radicals could not be unambiguously identified by NMR or EPR, the observation of PS80 oxidation products indicated their presence.LAY ABSTRACT: In our previously published work, we reported rapid polysorbate 80 (PS80) oxidation in a histidine buffer after brief exposure to stainless steel and the ability of citrate and EDTA to prevent this oxidation. The focus of our current study was to mechanistically understand PS80 oxidation by studying the impacts of temperature, light, and stainless steel and the role of citrate and EDTA. Additionally, PS80 oxidation was studied in three different buffer systems: histidine, citrate, and phosphate. The temperature study demonstrated that PS80 oxidation in the histidine or the citrate buffer systems is not initiated by temperature, but may be a factor in the phosphate buffer system. PS80 in the phosphate buffer system seemed to be the most vulnerable to light, as PS80 in both the histidine and the citrate buffer systems underwent oxidation at a lower level, with the histidine buffer system showing more rapid oxidation than the citrate buffer system. Finally, the ability of citrate and EDTA to act as not only chelators but also radical quenchers/scavengers was demonstrated when a metal ion, Fe2+, was spiked into the histidine buffer containing PS80. While neither NMR nor EPR could definitively identify the presence of free radicals, the observation of PS80 oxidation products indicates that they were present.

Role of citrate in the formation of enamel-like calcium phosphate oriented nanorod arrays

The effect of citrate on the formation of oriented fluoride doped hydroxyapatite nanorods grown on an amorphous calcium phosphate substrate was investigated.

Citrate reduced oxidative damage in stem cells by regulating cellular redox signaling pathways and represent a potential treatment for oxidative stress-induced diseases

Chemical substances containing citrate such as calcium citrate, citrate esters and citric acid exhibit anti-oxidant and anti-inflammatory properties in different cells and tissues. However, data on the anti-oxidant and anti-inflammatory properties and mechanisms of action of citrate are insufficient. In this study, we systematically evaluated the anti-oxidant capacity of citrate using chemical, cellular and animal assays. Citrate showed a stable molecular structure and did not directly react with oxides. Citrate exerted protective and anti-apoptotic effects on BMSCs and also showed significant inhibitory effects on the oxidative stress and inflammatory reactions in the rat air pouch model. By using proteomics, we found that PPARγ contributed to the upregulation of various free radical scavenging proteins and the downregulation of diverse components of the inflammatory responses. Citrate-regulated global PPARγ expression was evidenced by the significant increase expression of PPARγ in PC12 cell line. Our results provide novel insights into the role of citrate in regulating cellular redox signaling and the function of PPARγ signaling in this process and also provide basic molecular cell biology information to improve the applications of biomaterials or stem cells as treatments for oxidative stress-induced degenerative diseases and inflammatory diseases.

Role of Citrate and NaBr at the Surface of Colloidal Gold Nanoparticles during Functionalization

A molecular understanding of the ligand shell and the functionalization process is essential for the development of surface-functionalized gold nanoparticles (AuNPs). Obviously, the initial ligand ...

Monodisperse, colloidal and luminescent calcium fluoride nanoparticles via a citrate-assisted hydrothermal route

Luminescent calcium fluoride (CaF2) nanoparticles, because of their excellent biocompatibility, excellent photostability and strong fluorescence, have received increasing attention as drug carriers and bioprobes in cell imaging. Inspired by the role of citrate in the growth of apatite crystals during natural bio-mineralization, uniform and nearly monodisperse Eu3+-doped CaF2 nanoparticles with excellent colloidal stability and high fluorescence in aqueous media have been successfully synthesized in the presence of sodium citrate using a hydrothermal method. X-ray diffraction and transmission electron microscopy show that CaF2 nanoparticles grown in the presence of sodium citrate are cubes of relatively uniform size (15 nm), and that the Eu3+ doping level has little effect on size and morphology. Zeta potentials and dynamic light scattering demonstrate that in the synthesis with sodium citrate, the colloidal stability of CaF2 nanoparticles is greatly improved upon the increase of Eu3+ doping level. Moreover, aqueous dispersions of these nanoparticles are colloidally stable and can be maintained over a wide range of pH from 5.0 to 11.0 for more than a month. Fluorescence spectra demonstrate that the doped CaF2 nanoparticles display strong red fluorescence. Fourier transform infrared spectra and thermogravimetric analyses demonstrate the adsorption of substantial quantities of sodium citrate on the surfaces of the CaF2 nanoparticles. Taken together, such colloidal behavior should be related to strong crystal inhibition of citrate ions and Eu3+ doping induced promotion thermal-decomplexing between citrate ions and calcium ions. The luminescent CaF2 nanoparticles obtained using this protocol should be promising candidates for use in many bio-related applications.

The role of citrate, lactate and transferrin in determining titanium release from surgical devices into human serum.

The presence of ionic titanium in the serum of patients with titanium implants is currently unexplained. This is presumed due to corrosion, and yet the serum titanium concentration measured in patients is far greater than that predicted by its solubility. The binding of titanium ion as Ti(IV) to human transferrin (hTF) in serum indicates that Ti(IV) ions interact with human physiology. This is an intriguing finding since there is currently no known role for titanium ions in human physiology. Thus, understanding the factors that determine in vivo titanium ion release is relevant to further understanding this metal's interactions with human biochemistry. The present study sought to determine the extent of titanium ion release of into human serum in vitro, and the role of citrate, lactate and hTF in this process. It was found that, when surgical devices of commercially pure titanium were placed into human serum, citrate and lactate concentrations were the prime determinants of titanium release. Crystallography revealed Ti(IV) bound to hTF in the presence of citrate alone, signalling that citrate can act as an independent ligand for Ti(IV) binding to hTF. Based on these findings, a two-stage process of titanium ion release into human serum that is dependent upon both citrate and hTF is proposed to explain the ongoing presence of titanium ion in human subjects with implanted titanium devices.