Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS entry is required for locomotor and taste avoidance effects.

OBJECTIVES: Oxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure. METHODS AND RESULTS: We first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IP-injected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B12 (fCy5-OT-B12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBB-impermeable OT (OT-B12 ), with equipotent binding at OT-R in vitro. In vivo, IP-injected OT and OT-B12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression. CONCLUSIONS: Together our data indicate that limiting systemic OT CNS penetrance preserves the anorexic effects of the peptide and reduces the clinically undesired side effects of OT: emesis, taste avoidance and locomotor depression. Thus, therapeutic targeting of peripheral OT-R may be a viable strategy to achieve appetite suppression with better patient outcomes.

Synthesis and Chemical and Biological Evaluation of a Glycine Tripeptide Chelate of Magnesium.

Magnesium (Mg2+) plays a crucial role in over 80% of all metabolic functions. It is becoming increasingly apparent that magnesium deficiency (hypomagnesemia) may play an important role in chronic disease. To counteract magnesium deficiency, there is an unmet clinical need to develop new fully characterized, highly bioavailable, and substantially water-soluble magnesium supplements. To this end, triglycine (HG3), a tripeptide of the amino acid glycine, was chosen as a chelating ligand for magnesium, given its natural occurrence and water solubility, and entropically-driven metal binding. Herein, we discuss the synthesis, chemical and physical characterization, and cellular uptake of a magnesium triglycine chelate (MgG3), an octahedral complex with extraordinary water solubility and improved cellular uptake in CaCo-2 cells than select commonly used magnesium supplements.

Nonconventional glucagon and GLP-1 receptor agonist and antagonist interplay at the GLP-1 receptor revealed in high-throughput FRET assays for cAMP.

G protein-coupled receptors (GPCRs) for glucagon (GluR) and glucagon-like peptide-1 (GLP-1R) are normally considered to be highly selective for glucagon and GLP-1, respectively. However, glucagon secreted from pancreatic α-cells may accumulate at high concentrations to exert promiscuous effects at the ß-cell GLP-1R, as may occur in the volume-restricted microenvironment of the islets of Langerhans. Furthermore, systemic administration of GluR or GLP-1R agonists and antagonists at high doses may lead to off-target effects at other receptors. Here, we used molecular modeling to evaluate data derived from FRET assays that detect cAMP as a read-out for GluR and GLP-1R activation. This analysis established that glucagon is a nonconventional GLP-1R agonist, an effect inhibited by the GLP-1R orthosteric antagonist exendin(9-39) (Ex(9-39)). The GluR allosteric inhibitors LY2409021 and MK 0893 antagonized glucagon and GLP-1 action at the GLP-1R, whereas des-His1-[Glu9]glucagon antagonized glucagon action at the GluR, while having minimal inhibitory action versus glucagon or GLP-1 at the GLP-1R. When testing Ex(9-39) in combination with des-His1-[Glu9]glucagon in INS-1 832/13 cells, we validated a dual agonist action of glucagon at the GluR and GLP-1R. Hybrid peptide GGP817 containing glucagon fused to a fragment of peptide YY (PYY) acted as a triagonist at the GluR, GLP-1R, and neuropeptide Y2 receptor (NPY2R). Collectively, these findings provide a new triagonist strategy with which to target the GluR, GLP-1R, and NPY2R. They also provide an impetus to reevaluate prior studies in which GluR and GLP-1R agonists and antagonists were assumed not to exert promiscuous actions at other GPCRs.

A second-generation glucagon-like peptide-1 receptor agonist mitigates vomiting and anorexia while retaining glucoregulatory potency in lean diabetic and emetic mammalian models.

AIM: To develop a conjugate of vitamin B12 bound to the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex4) that shows reduced penetrance into the central nervous system while maintaining peripheral glucoregulatory function. METHODS: We evaluated whether a vitamin B12 conjugate of Ex4 (B12-Ex4) improves glucose tolerance without inducing anorexia in Goto-Kakizaki (GK) rats, a lean type 2 diabetes model of an understudied but medically compromised population of patients requiring the glucoregulatory effects of GLP-1R agonists without anorexia. We also utilized the musk shrew (Suncus murinus), a mammalian model capable of emesis, to test B12-Ex4 on glycaemic profile, feeding and emesis. RESULTS: In both models, native Ex4 and B12-Ex4 equivalently blunted the rise in blood glucose levels during a glucose tolerance test. In both GK rats and shrews, acute Ex4 administration decreased food intake, leading to weight loss; by contrast, equimolar administration of B12-Ex4 had no effect on feeding and body weight. There was a near absence of emesis in shrews given systemic B12-Ex4, in contrast to reliable emesis produced by Ex4. When administered centrally, both B12-Ex4 and Ex4 induced similar potency of emesis, suggesting that brain penetrance of B12-Ex4 is required for induction of emesis. CONCLUSIONS: These findings highlight the potential therapeutic value of B12-Ex4 as a novel treatment for type 2 diabetes devoid of weight loss and with reduced adverse effects and better tolerance, but similar glucoregulation to current GLP-1R agonists.

A vitamin B12 conjugate of exendin-4 improves glucose tolerance without associated nausea or hypophagia in rodents.

AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 (B12) bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice. To evaluate whether differences in the profile of effects of B12-Ex4 vs unconjugated Ex4 are the result of altered CNS penetrance, rats received systemic injections of fluorescein-Ex4 (Flex), Cy5-B12 or Cy5-B12-Ex4 and brain penetrance was evaluated using confocal microscopy. Uptake of systemically administered Cy5-B12-Ex4 in insulin-containing pancreatic beta cells was also examined. RESULTS: B12-Ex4 conjugate improves glucose tolerance, but does not elicit the malaise and anorexia produced by unconjugated Ex4. While Flex robustly penetrates into the brain (dorsal vagal complex, paraventricular hypothalamus), Cy5-B12 and Cy5-B12-Ex4 fluorescence were not observed centrally, supporting an absence of CNS penetrance, in line with observed reduction in CNS-associated Ex4 side effects. Cy5-B12-Ex4 colocalizes with insulin in the pancreas, suggesting direct pancreatic action as a potential mechanism underlying the hypoglycaemic effects of B12-Ex4. CONCLUSION: These novel findings highlight the potential clinical utility of B12-Ex4 conjugates as possible future T2DM therapeutics with reduced incidence of adverse effects.

Metal-citrate complex transport in Kineococcus radiotolerans.

The growth of an organism is highly dependent on the acquisition of carbon and metals, and availability of these nutrients in the environment affects its survival. Organisms can obtain both nutrients simultaneously through proteins of the CitMHS superfamily. Bioinformatic studies suggested a CitMHS gene (Accession number ABS03965.1) in Kineococcus radiotolerans. Radio flux assays following 14-C radiolabelled citrate, either free or complexed to a variety of metal ions, in K. radiotolerans demonstrated internalization of the citrate when bound to select metal ions only, primarily in the form of calcium-citrate. A pH response was also observed, consistent with a permease (ATP independent) mechanism as noted for other CitMHS family members, with greater uptake at pH 7 compared to pH 10. These results confirm the ability of K. radiotolerans to transport complexed citrate.

Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.

Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin ß. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 µg/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 µg/mL of chymotrypsin, and there was no decrease in function at up to 5 µg/mL of meprin ß.

Ferromagnetic Coupling in "Double-Bridged" Dihydrogenpyrophosphate Complexes of Cobalt(II) and Nickel(II).

Three isostructural compounds of the formula {[M(bipy)(H2O)(H2P2O7)]2·2H2O} [bipy = 2,2'-bipyridine; M = Ni (1), Co (2), Mn (3)] have been isolated from aqueous solutions containing the corresponding metal(II) chloride hydrate with a bipy and sodium pyrophosphate solution in a 1:1:2 molar ratio, and their structures were determined by single-crystal X-ray diffraction. The structures of 1-3 consist of neutral aqua(2,2'-bipyridine)metal(II) dinuclear units bridged by two dihydrogenpyrophosphate groups adopting a bidentate/monodentate mode. Each metal ion in 1-3 is six-coordinate in a distorted octahedral geometry, with the reduced value of the angle subtended by the chelating bipy at the metal ion [79.6(1)° (1), 77.32(7)° (2), and 72.9(1)° (3)] being the main source of this distortion. The values of the intramolecular metal-metal separation are 5.271(1) Å (1), 5.3065(8) Å (2), and 5.371(1) Å (3). Magnetic susceptibility measurements on polycrystalline samples of 1-3 in the temperature range 1.9-300 K shows weak intramolecular ferromagnetic [J = +1.86(2) cm(-1) (1) and +0.25(1) cm(-1) (2)] and antiferromagnetic [J = -0.48(1) cm(-1) (3)] coupling, with the spin Hamiltonian being defined as H = -JSM1·SM1a. This rarely observed coordination mode for dihydrogenpyrophosphate leads to ferromagnetic coupling in complexes of nickel(II) or cobalt(II).

Clinical isolates of Candida albicans, Candida tropicalis, and Candida krusei have different susceptibilities to Co(II) and Cu(II) complexes of 1,10-phenanthroline.

The minimal inhibitory concentrations (MICs) of copper and cobalt based dimeric pyrophosphate complexes with capping 1,10-phenanthroline groups on clinical isolates of C. albicans (28 isolates), C. krusei (20 isolates) and C. tropicalis (20 isolates) are reported. C. albicans was inhibited by the cobalt complex better than by the copper complex, while C. krusei demonstrated the opposite results. C. tropicalis showed similar sensitivities to both metals in terms of calculated MIC50 values but was more sensitive to cobalt when MIC90 values were noted. Knockout strains of C. albicans that had the copper efflux protein P-type ATPase (CRP1), the copper binding metallothionein CUP1 or both CRP1/CUP1 removed clearly demonstrate that the origins of copper resistant in C. albicans lies primarily in the P-type ATPase, with the MT playing an important secondary role in the absence of the efflux protein. This study suggests that certain strains of Candida have evolved to protect against particular metal ions and that in the case of C. albicans, a primary invasive fungal species, cobalt may be a good starting-point for new therapeutic development.

Single amino acid chelate complexes of the M(CO)3 (+) core for correlating fluorescence and radioimaging studies (M = (99m) Tc or Re).

Single amino acid chelates (SAACs) and SAAC-like bifunctional ligands can be exploited in the design of a variety of bioconjugates for facile metallation with the M(CO)3 (+) unit with M = (99m) Tc or Re. When the donor groups of the ligand are quinolone, thiazole or other similarly conjugated heterocycles, the rhenium complexes are fluorescent, affording complementary and isostructural fluorescent probes to the radioactive (99m) Tc analogues. The versatility of the approach has been demonstrated by the preparation of bioconjugates incorporating peptides, biotin, folic acid, thymidine and vitamin B12 . In addition, the unusual photophysical properties observed for rhenium of the [bisthiazole-diamino butane-Re(CO)3 (+) ] derivative [BTBA-Re(CO)3 ](+) are discussed.

Corrination mitigates peptide aggregation as exemplified for Glucagon.

Pharmaceutical development of glucagon for use in acute hypoglycemia has proved challenging, due in large part to poor solubility, poor stability and aggregate formation. Herein, we describe highly soluble, low aggregating, glucagon conjugates generated through use of the commercially available vitamin B12 precursor dicyanocobinamide ('corrination'), which retain full stimulatory action at the human glucagon receptor. The modified glucagon analogs were tested in a chemical stability assay in 50 mM phosphate buffer and the percentage of original concentration retained was determined after two weeks of incubation at 37° C. Aggregate formation assays were also performed after 48 h of agitation at 37°C using a thioflavin (ThT) fluorescence-based assay. All corrinated compounds retained original concentration to a higher degree than glucagon controls and showed markedly decreased aggregation compared to their respective noncorrinated analogues. Based on the statistically significant increase in chemical stability coupled with the notably decreased tendency to form aggregates, analogues 2 and its corrinated conjugate 5 were used for a functional assay study performed after agitation at 37°C for 24-hr after which agonism was measured at the human glucagon receptor using a cAMP FRET assay. Corrinated 5 exhibited a 6.6-fold increased potency relative to glucagon, which was shown to have a 165-fold reduction in potency. The relative potency of 5 was also improved compared to that of 2 with EC50 values of 5.5 nM and 9.6 nM for 5 and 2, respectively. In conclusion, corrination of peptides mitigates aggregation, presenting a compound with prolonged stability and agonism as demonstrated for glucagon.

Reductions of food intake and body weight in diet-induced obese rats following chronic treatment with a monomeric peptide multiagonist.

INTRODUCTION: While therapies based on endogenous gut peptides such as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have been compelling therapeutic agents for obesity and type 2 diabetes (T2D), only a few have achieved long-term weight loss and all have shown significant side-effects, including nausea/malaise and gastrointestinal ailments. OBJECTIVE: As the pathophysiology of obesity is driven by dysregulation of multiple, inter-related, pathways, we tested a novel peptide targeting multiple receptors of complementary neurocircuits regulating the controls of energy balance. METHODS: Response to daily injections of GEP44, a GLP-1R and neuropeptide Y1R and Y2R receptor (Y1R/Y2R) triple agonist was tested vs. the GLP-1R agonist liraglutide (LIRA) in diet-induced obese (DIO) male and female rats. Glucose tolerance tests after intraperitoneal injection of glucose (IPGTT) were performed at baseline and after 14-d of treatment in GEP44 treated rats. Other metabolic parameters were assessed in blood at the end of a 28-d intervention. RESULTS: Upon conclusion at 28-d, body weight reduction compared to vehicle was -15.6%/-11.9% in response to GEP44, vs. -9.7%/-5.1% after LIRA, males, and females, respectively. Significant reductions of cumulative food intake occurred over 28-d in female rats treated with GEP44 (-30%; p < 0.0001), vs. LIRA (-10%), and in male rats GEP44 (-39%; p < 0.0001), vs. LIRA (-20%; p = 0.003). In IPGTTs, a similar stimulation glucose induced insulin secretion was noted in rats treated with GEP44 and LIRA. CONCLUSION: The strong reductions of body weight in response to long-term applications of the triple agonist GEP44 confirms the therapeutic potential of targeting multiple receptors for achieving more robust and potentially more sustained improvement of energy balance.

The Novel Chimeric Multi-Agonist Peptide (GEP44) Reduces Energy Intake and Body Weight in Male and Female Diet-Induced Obese Mice in a Glucagon-Like Peptide-1 Receptor-Dependent Manner.

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R +/+ mice and GLP-1R null (GLP-1R -/- ) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R +/+ mice by - 1.5±0.6, -1.3±0.4 and -1.9±0.4 grams, respectively ( P <0.05), with similar effects being observed in female GLP-1R +/+ mice. These effects were absent in male and female DIO GLP-1R -/- mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R +/+ mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R -/- mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R +/+ mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.

Secondary transport of metal-citrate complexes: the CitMHS family.

Primary and secondary transport of citrate has been extensively studied in pathogenic and non-pathogenic bacteria. Primary transporters of citrate complexed with metal ions, particularly Fe, have also garnered attention, with the fec system of E. coli being a classic example. In contrast, little is known about secondary transporters of metal-citrate complexes. Recently, a family of proteins responsible for secondary metal-citrate transport in bacteria was discovered and designated as the CitMHS transporter family. Several members have been functionally characterized to date and serve as the foundation for understanding this family. Three subfamilies have been categorized, depending on the main metal ion transported. These subfamilies are the Mg(2+)-citrate transporter, the Ca(2+)-citrate transporter, and the Fe(3+)-citrate transporter. Each subfamily is believed to be substrate-selective due to the metal-citrate complexes being abundantly present in their environment and/or the ability of the complex to be metabolized by the organism. The implication of this family in the pathogenic access to Fe, information about transcriptional control, putative structure, predicted family members, members characterized to date and potential use in bioremediation are discussed.

Rapid, green disulphide bond formation in water using the corrin dicyanocobinamide.

Peptide chemists seek rapid methods combined with facile purification when producing disulphide bonds post solid-phase synthesis. Current methods typically require long reaction times of up to two days, can result in side-products from over-oxidation and/or degradation, require organic solvents, and/or require challenging purification. Herein, we describe a rapid, green, and facile oxidation of a series of peptides with up to three disulphide bonds. The method was conducted in aqueous solution, in air, utilizing the biocompatible corrin ring-containing compound dicyanocobinamide, and offers reaction times under 1 hour with simple one step removal of the catalyst.

Creation of a Peptide Antagonist of the GFRAL-RET Receptor Complex for the Treatment of GDF15-Induced Malaise.

Growth differentiation factor 15 (GDF15) is a contributor to nausea, emesis, and anorexia following chemotherapy via binding to the GFRAL-RET receptor complex expressed in hindbrain neurons. Therefore, GDF15-mediated GFRAL-RET signaling is a promising target for improving treatment outcomes for chemotherapy patients. We developed peptide-based antagonists of GFRAL that block GDF15-mediated RET recruitment. Our initial library screen led to five novel peptides. Surface plasmon resonance and flow cytometric analyses of the most efficacious of this group, termed GRASP, revealed its capacity to bind to GFRAL. In vivo studies in rats revealed that GRASP could attenuate GDF15-induced nausea and anorexia resulting from cisplatin. Combined with Ondansetron, GRASP led to an even greater attenuation of the anorectic effects of cisplatin compared to either agent alone. Our results highlight the beneficial effects of GRASP as an agent to combat chemotherapy-induced malaise. GRASP may also be effective in other conditions associated with elevated levels of GDF15.

A peptide triple agonist of GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors promotes glycemic control and weight loss.

Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissue ex vivo and more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.

Expression and purification of human PYY(3-36) in Escherichia coli using a His-tagged small ubiquitin-like modifier fusion.

Human PYY(3-36) (hPYY3-36) is a 34 amino acid hormone that has received a great deal of attention due to its effects on appetite regulation. hPYY(3-36) was modified at the N-terminus with an octahistidine tag and factor Xa protease sequence along with the small ubiquitin-like modifier (SUMO) tag and expressed in Escherichia coli. The protein was purified from clarified E. coli lysate by immobilized metal affinity chromatography (IMAC) with a yield of 30±7 mg/L of induced culture returned as an average over seven runs, and its identity was confirmed by Western blot and hPYY antibody recognition. The SUMO-tagged hPYY(3-36) was digested with two different proteases to return either His-tagged hPYY(3-36) or unmodified hPYY(3-36): (1) digestion with SUMO protease proceeded at about 50% efficiency yielding His-tagged hPYY(3-36); (2) digestion with factor Xa protease proceeded at greater than 90% efficiency yielding final hPYY(3-36). Products were purified from the digestion mixtures by reverse-phase high-performance liquid chromatography (C(18)) or IMAC, respectively, the identities were confirmed by mass spectrometry and hPYY antibody recognition, and the folded state of His-tagged hPYY(3-36) was investigated by circular dichroism spectroscopy.

Pyro without fire: synthesis, structure, and reactivity of a dimeric vanadyl pyrophosphate coordination complex.

The complex {[(V(IV)O)bipy(H(2)O)](2)(µ-P(2)O(7))}·3H(2)O (2) was readily obtained as a nanocrystalline powder by one-pot synthesis under mild conditions. Single crystals of 2 were grown at room temperature over 2 months, and its structure was determined. Fundamental catalytic activity was proven for this species by testing for oxidation of benzyl alcohol in air.