Microglial P2Y12 Signaling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord.

Administration of cisplatin and other chemotherapy drugs is crucial for treating tumors. However, cisplatin-induced pain hypersensitivity is still a critical clinical issue, and the underlying molecular mechanisms have remained unresolved to date. In this study, we found that repeated cisplatin treatments remarkedly upregulated the P2Y12 expression in the spinal cord. Expression of P2Y12 was predominant in the microglia. Pharmacological inhibition of P2Y12 expression markedly attenuated the cisplatin-induced pain hypersensitivity. Meanwhile, blocking the P2Y12 signal also suppressed cisplatin-induced microglia hyperactivity. Furthermore, the microglia Src family kinase/p38 pathway is required for P2Y12-mediated cisplatin-induced pain hypersensitivity via the proinflammatory cytokine IL-18 production in the spinal cord. Blocking the P2Y12/IL-18 signaling pathway reversed cisplatin-induced pain hypersensitivity, as well as activation of N-methyl-D-aspartate receptor and subsequent Ca2+-dependent signals. Collectively, our data suggest that microglia P2Y12-SFK-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal, and P2Y12 could be a potential target for intervention to prevent chemotherapy-induced pain hypersensitivity. PERSPECTIVE: Our work identified that P2Y12/IL-18 played a critical role in cisplatin-induced pain hypersensitivity. This work suggests that P2Y12/IL-18 signaling may be a useful strategy for the treatment of chemotherapy-induced pain hypersensitivity.

Axial Ligand as a Critical Factor for High-Performance Pentagonal Bipyramidal Dy(III) Single-Ion Magnets.

The choice of axial ligands is of great importance for the construction of high-performance Dy-based single-molecule magnets (SMMs). Here, combining axial ligands Ph3SiO- (anion of triphenylsilanol) and 2,6-dichloro-4-nitro-PhO- (the anion of 2,6-dichloro-4-nitrophenol) with a neutral macrocyclic ligand 2,14-dimethyl-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),2,13,15,17-pentaene (L2N5) generates two new pentagonal bipyramidal Dy(III) complexes [DyIII(L2N5) (X)2](BPh4) (X = Ph3SiO-, 1; 2,6-dichloro-4-nitro-PhO-, 2) with strong axial ligand fields. Magnetic characterizations show that 1 possesses a large energy barrier above 1000 K and a magnetic hysteresis up to 9 K, whereas 2 only displays field-induced peaks of alternating-current susceptibilities without the hysteresis loop, even though 2 has a similar coordination geometry with 1. Detailed Ab initio calculations indicate an apparent difference in the axial negative charge between both complexes, which is caused by the diverse electron-donating properties of the axial ligands. The present work provides an efficient strategy to enhance the SMMs' properties, which highlights that the electron-donating property of the axial ligands is especially important for constructing the high-performance Dy-based SMMs.

Metabolism of Paeoniae Radix Rubra and its 14 constituents in mice.

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time. Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MSn). Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3'-di-O-methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation. Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR.

Layered Uranyl Phosphonates Encapsulating Co(II)/Mn(II)/Zn(II) Ions: Exfoliation into Nanosheets and Its Impact on Magnetic and Luminescent Properties.

Layered heterometallic 5f-3d uranyl phosphonates can exhibit unique luminescent and/or magnetic properties, but the fabrication and properties of their 2D counterparts have not been investigated. Herein we report three heterobimetallic uranyl phosphonates, namely, [(UO2 )3 M(2-pmbH)4 (H2 O)4 ] ⋅ 2H2 O [MU, M=Co(II), CoU; Mn(II), MnU; Zn(II), ZnU; 2-pmbH3 =2-(phosphonomethyl)benzoic acid]. They are isostructural and display two-dimensional layered structures where the M(II) centers are encapsulated inside the windows generated by the diamagnetic uranyl phosphonate layer. Each M(II) has an octahedral geometry filled with four water molecules in the equatorial positions and two phosphonate oxygen atoms in the axial positions. The uranium atoms adopt UO7 pentagonal bipyramidal and UO6 square bipyramidal geometries. The lattice and coordination water molecules can be released by thermal treatment and reabsorbed in a reversible manner, accompanied with changes of magnetic dynamics. Interestingly, the bulk samples of MU can be exfoliated in acetone via freezing and thawing processes forming nanosheets with single-layer or two-layer thickness (MU-ns). Magnetic studies revealed that the CoU and MnU systems exhibited field-induced slow magnetization relaxation at low temperature. Compared with crystalline CoU, the magnetic relaxation of the CoU-ns aggregates is significantly accelerated. Moreover, photoluminescence measured at 77 K showed slight red-shift of the five characteristic uranyl emission bands for ZnU-ns in comparison with those of the crystalline ZnU. This work gives the first examples of 2D materials based on 5f-3d heterometallic uranyl phosphonates and illustrates the impact of dimension reduction on their magnetic/optical properties.

Magnetic anisotropy of two tetrahedral Co(II)-halide complexes with triphenylphosphine ligands.

Recently, the choice of ligand and geometric control of mononuclear complexes, which can affect the relaxation pathways and blocking temperature, have received wide attention in the field of single-ion magnets (SIMs). To find out the influence of the coordination environment on SIMs, two four-coordinate mononuclear Co(II) complexes [NEt4][Co(PPh3)X3] (X = Cl-, 1; Br-, 2) have been synthesized and studied by X-ray single crystallography, magnetic measurements, high-frequency and -field EPR (HF-EPR) spectroscopy and theoretical calculations. Both complexes are in a cubic space group Pa3̄ (No. 205), containing a slightly distorted tetrahedral moiety with crystallographically imposed C3v symmetry through the [Co(PPh3)X3]- anion. The direct-current (dc) magnetic data and HF-EPR spectroscopy indicated the anisotropic S = 3/2 spin ground states of the Co(II) ions with the easy-plane anisotropy for 1 and 2. Ab initio calculations were performed to confirm the positive magnetic anisotropies of 1 and 2. Frequency- and temperature-dependent alternating-current (ac) magnetic susceptibility measurements revealed slow magnetic relaxation for 1 and 2 at an applied dc field. Finally, the magnetic properties of 1 and 2 were compared to those of other Co(II) complexes with a [CoAB3] moiety.

Vascular endothelial growth factor-A/vascular endothelial growth factor2 signaling in spinal neurons contributes to bone cancer pain.

Tumor metastasis to bone is often accompanied by a severe pain syndrome (cancer-induced bone pain, CIBP) that is frequently unresponsive to analgesics, which markedly reduces patient quality of life and cancer treatment tolerance in patients. Prolonged pain can induce hypersensitivity via spinal plasticity, and several recent studies have implicated the involvement of vascular endothelial growth factor-A (VEGF-A) signaling in this process. Here, we speculated that CIBP is associated with VEGF-A/VEGFR2 signaling in the spinal cord. A mouse model of CIBP was established by intramedullary injection of Lewis lung carcinoma (LLC) cells in the mouse femur. Pain sensitization and potential amelioration via VEGF-A/VEGFR2 blockade were measured using paw withdrawal threshold to mechanical stimulation and paw withdrawal latency to thermal. Spinal VEGF-A/VEGFR2 signaling was blocked by intrathecal injection of the VEGF-A antibody or the specific VEGFR2 inhibitor ZM323881. Changes in the expression levels of VEGF-A, VEGFR2, and other pain-related signaling factors were measured using western blotting and immunofluorescence staining. Mice after LLC injection demonstrated mechanical allodynia and thermal hyperalgesia, both of which were suppressed via anti-VEGF-A antibody or ZM323881. Conversely, the intrathecal injection of exogenous VEGF-A was sufficient to cause pain hypersensitivity in naïve mice via the VEGFR2-mediated activation of protein kinase C. Moreover, the spinal blockade of VEGF-A or VEGFR2 also suppressed N-methyl-D-aspartate receptor (NMDAR) activation and downstream Ca2+-dependent signaling. Thus, spinal VEGF-A/VEGFR2/NMDAR signaling pathways may be critical mediators of CIBP.

Magnetic anisotropy in square pyramidal cobalt(II) complexes supported by a tetraazo macrocyclic ligand.

Two five-coordinate mononuclear Co(ii) complexes [Co(12-TMC)X][B(C6H5)4] (L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane (12-TMC), X = Cl- (1), Br- (2)) have been studied by X-ray single crystallography, magnetic measurements, high-frequency and -field EPR (HF-EPR) spectroscopy and theoretical calculations. Both complexes have a distorted square pyramidal geometry with the Co(ii) ion lying above the basal plane constrained by the rigid tetradentate macrocyclic ligand. In contrast to the reported five-coordinate Co(ii) complex [Co(12-TMC)(NCO)][B(C6H5)4] (3) exhibiting easy-axis anisotropy, an easy-plane magnetic anisotropy was found for 1 and 2via the analyses of the direct-current magnetic data and HF-EPR spectroscopy. Frequency- and temperature-dependent alternating-current magnetic susceptibility measurements demonstrated that complexes 1 and 2 show slow magnetic relaxation at an applied dc field. Ab initio calculations were performed to reveal the impact of the terminal ligands on the nature of the magnetic anisotropies of this series of five-coordinate Co(ii) complexes.

Role of the CXCR4/ALK5/Smad3 Signaling Pathway in Cancer-Induced Bone Pain.

PURPOSE: The chemokine receptor, CXCR4, and the transforming growth factor-beta receptor, ALK5, both contribute to various processes associated with the sensation of pain. However, the relationship between CXCR4 and ALK5 and the possible mechanisms promoted by ALK5 in the development of pain have not been evaluated. MATERIALS AND METHODS: Tumor cell implantation (TCI) technology was used to generate a model of cancer-induced bone pain (CIBP) in rats; intrathecal (i.t.) injections of small interfering (si) RNAs targeting CXCR4 and the ALK5-specific inhibitor, RepSox, were performed. Behavioral outcomes, Western blotting, and immunofluorescence techniques were used to evaluate the expression of the aforementioned specific target proteins in the CIBP model. RESULTS: The results revealed that i.t. administration of siRNAs targeting CXCR4 resulted in significant reductions in both mechanical and thermal hyperalgesia in rats with CIBP and likewise significantly reduced the expression of ALK5 in the spinal cord. Similarly, i.t. administration of RepSox also resulted in significant reductions in mechanical and thermal hyperalgesia in rats with CIBP together with diminished levels of spinal p-Smad3. CONCLUSION: Taken together, our results suggest that CXCR4 expression in the spinal cord may be a critical mediator of CIBP via its capacity to activate ALK5 and downstream signaling pathways.

Structure, magnetic anisotropy and relaxation behavior of seven-coordinate Co(ii) single-ion magnets perturbed by counter-anions.

A series of mononuclear seven-coordinate Co(ii) complexes [CoII(BPA-TPA)](ClO4)2·H2O (2-ClO4), [CoII(BPA-TPA)](PF6)2 (3-PF6) and [CoII(BPA-TPA)](BPh4)2 (4-BPh4) have been synthesized based on the ligand 2,6-bis(bis(2-pyridylmethyl)amino)methylpyridine (BPA-TPA), and their structures have been characterized by single-crystal X-ray diffraction. All these complexes feature an intermediate coordination polyhedron between a capped trigonal prism and a capped octahedron, which is perturbed by the variation of the counter anions. Easy-plane magnetic anisotropies for all complexes were revealed via the analyses of the direct-current magnetic data and high-field electron paramagnetic resonance (HFEPR) spectra. They show slow magnetic relaxation under applied direct current field, which is similar to the previously reported complex [CoII(BPA-TPA)](BF4)2 (1-BF4) with a capped trigonal prism. This work provides a new example of modulating the properties of single-ion magnets (SIMs) by changing the counter anions.

Chemokine receptor CXCR4 activates the RhoA/ROCK2 pathway in spinal neurons that induces bone cancer pain.

BACKGROUND: Chemokine receptor CXCR4 has been found to be associated with spinal neuron and glial cell activation during bone cancer pain. However, the underlying mechanism remains unknown. Furthermore, the RhoA/ROCK2 pathway serves as a downstream pathway activated by CXCR4 during bone cancer pain. We first validated the increase in the expressions of CXCR4, p-RhoA, and p-ROCK2 in the spinal dorsal horn of a well-characterized tumor cell implantation-induced cancer pain rat model and how these expressions contributed to the pain behavior in tumor cell implantation rats. We hypothesized that spinal blockade of the CXCR4-RhoA/ROCK2 pathway is a potential analgesic therapy for cancer pain management. METHODS: Adult female Sprague-Dawley rats (body weight of 180-220 g) and six- to seven-week old female Sprague-Dawley rats (body weight of 80-90 g) were taken. Ascitic cancer cells were extracted from the rats (body weight of 80-90 g) with intraperitoneally implanted Walker 256 mammary gland carcinoma cells. Walker 256 rat mammary gland carcinoma cells were then injected (tumor cell implantation) into the intramedullary space of the tibia to establish a rat model of bone cancer pain. RESULTS: We found increased expressions of CXCR4, p-RhoA, and p-ROCK2 in the neurons in the spinal cord. p-RhoA and p-ROCK2 were co-expressed in the neurons and promoted by overexpressed CXCR4. Intrathecal delivery of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil abrogated tumor cell implantation-induced pain hypersensitivity and tumor cell implantation-induced increase in p-RhoA and p-ROCK2 expressions. Intrathecal injection of stromal-derived factor-1, the principal ligand for CXCR4, accelerated p-RhoA expression in naive rats, which was prevented by postadministration of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil. CONCLUSIONS: Collectively, the spinal RhoA/ROCK2 pathway could be a critical downstream target for CXCR4-mediated neuronal sensitization and pain hypersensitivity in bone cancer pain, and it may serve as a potent therapeutic target for pain treatment.

A capped trigonal prismatic cobalt(ii) complex as a structural archetype for single-ion magnets.

Two mononuclear, seven-coordinate Co(ii) and Fe(ii) complexes [CoII(BPA-TPA)](BF4)2 (1-Co) and [FeII(BPA-TPA)](ClO4)2 (2-Fe) with a capped trigonal prismatic coordination geometry have been synthesized from the pentapyridyldiamine (BPA-TPA) ligand. 1-Co exhibits easy plane anisotropy in which slow magnetic relaxation is observed under a 1.0 kOe dc field. It is the first example of a single-ion magnet (SIM) of a 3d transition metal ion with a capped trigonal prismatic configuration. 2-Fe is not a SIM at 1.8 K.

Spectroscopic Studies of the Magnetic Excitation and Spin-Phonon Couplings in a Single-Molecule Magnet.

Large separations between ground and excited magnetic states in single-molecule magnets (SMMs) are desirable to reduce the likelihood of spin reversal in the molecules. Spin-phonon coupling is a process leading to magnetic relaxation. Both the reversal and coupling, making SMMs lose magnetic moments, are undesirable. However, direct determination of large magnetic states separations (>45 cm-1 ) is challenging, and few detailed investigations of the spin-phonon coupling have been conducted. The magnetic separation in [Co(12-crown-4)2 ](I3 )2 (12-crown-4) (1) is determined and its spin-phonon coupling is probed by inelastic neutron scattering (INS) and far-IR spectroscopy. INS, using oriented single crystals, shows a magnetic transition at 49.4(1.0) cm-1 . Far-IR reveals that the magnetic transition and nearby phonons are coupled, a rarely observed phenomenon, with spin-phonon coupling constants of 1.7-2.5 cm-1 . The current work spectroscopically determines the ground-excited magnetic states separation in an SMM and quantifies its spin-phonon coupling, shedding light on the process causing magnetic relaxation.

Zero-Field Slow Magnetic Relaxation and Hysteresis Loop in Four-Coordinate CoII Single-Ion Magnets with Strong Easy-Axis Anisotropy.

Two mononuclear tetrahedral Co(II) complexes (HNEt3)2[Co(L1)2]·H2O (1) and (Bu4N)2[Co(L2)2]·H2O (2) (H2L1 = N,N'-bis(p-toluenesulfony1)oxamide, H2L2 = N,N'-diphenyloxamide) have been synthesized, and their structures have been characterized by single-crystal X-ray diffraction. Both complexes adopt distorted tetrahedral coordination geometries surrounding the Co(II) center, which is ligated by two doubly deprotonated oxamide ligands oriented perpendicularly to each other. Their axial magnetic anisotropies were revealed by the direct current (dc) magnetic measurements, high-field and high-frequency electron paramagnetic resonance, and theoretical calculations. Both complexes display slow magnetic relaxation in the absence of an applied dc field. Upon the application of the 0.15 T dc field, the quantum tunneling of magnetization is efficiently suppressed. In addition, both complexes display hysteresis loops with different field sweep rates at 1.8 K, which is rarely observed for Co(II) single-ion magnets (SIMs).

Magnetic anisotropy and slow magnetic relaxation processes of cobalt(ii)-pseudohalide complexes.

Three mononuclear six-coordinate Co(ii)-pseudohalide complexes [Co(L)X2] with two N-donor pseudohalido coligands occupying the cis-positions (X = NCS- (1), NCSe- (2) or N(CN)2- (3)), and a five-coordinate complex [Co(L)(NCO)][B(C6H5)4] (4) [L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane (12-TMC)] have been prepared and structurally characterized. Easy-plane magnetic anisotropy for 1-3 and easy-axis anisotropy for 4 were revealed via the analyses of the direct-current magnetic data, high-frequency and -field EPR (HFEPR) spectra and ab initio theoretical calculations. They display slow magnetic relaxations under an external applied dc field. Typically, two slow relaxation processes were found in 1 and 2 while only one relaxation process occurs in 3 and 4. The Raman-like mechanism is found to be dominant in the studied temperature range in 1. For 2-4, the Raman process is dominant in the low temperature region, while the Orbach mechanism dominates in the high temperature range.

Single-Crystal Study of a Low Spin Co(II) Molecular Qubit: Observation of Anisotropic Rabi Cycles.

A mononuclear low spin ( S = 1/2) Co(II) molecule crystallized in a 4-fold symmetry is fully investigated by CW and pulsed EPR on a single crystal sample. The quantum phase memory time of the molecule around 1 µs at 5 K is direction-independent, while the Rabi oscillation frequency is anisotropic. The spin Hamiltonian analyses reveal that the anisotropic Landé factor and hyperfine tensor do not influence the anisotropy apparently when the microwave magnetic field is applied along a certain direction. It is considered that the possibly involved nuclear spin forbidden transitions may be responsible for the small distinction of Rabi frequencies in two directions.

Luminescent Mechanochromic Dinuclear Cu(I) Complexes with Macrocyclic Diamine-Tetracarbene Ligands.

Dinuclear Cu(I) complexes bearing hexadentate, macrocyclic N-heterocyclic carbene (NHC) ligands, [Cu2(L1)(CH3CN)][PF6]2 (1) and [Cu2(L2)(CH3CN)]2[Cu2(L2)(CH3CN)2][PF6]6 (2), have been synthesized by the reactions of [H4L][PF6]4 (L = L1, L2) with excess Cu2O in acetonitrile. Crystallizations of the heat-treated samples of 1 and 2 from acetone/methanol/ether or CH3NO2/ether result in [Cu2(L1)][PF6]2 (3) and [Cu2(L2)][PF6]2 (4). Complexes 1-4 are emissive with luminescent maxima at 464, 472, 540, and 488 nm in the solid state, respectively. The origin of the red shift of the emission maximum of 3 relative to the other three complexes has been studied by theoretical calculations, showing the cuprophilic interactions in the excited state of 3. The mechanochromic luminescent properties of 1-4 have been studied. After grinding in a mortar, a significant emission color change is found with a red shift of 98 nm for 1, 82 nm for 2, 20 nm for 3, and 64 nm for 4, respectively. These mechanochromic transformations are found to be a crystalline-to-amorphous conversion, which can be reverted by adding drops of the organic solvent or recrystallization. The possible correlations between the luminescent properties and structural modifications such as Cu···Cu distances are discussed.

Magnetic anisotropy and relaxation behavior of six-coordinate tris(pivalato)-Co(ii) and -Ni(ii) complexes.

Experimental and theoretical studies of magnetic anisotropy and relaxation behavior of six-coordinate tris(pivalato)-Co(ii) and -Ni(ii) complexes (NBu4)[M(piv)3] (piv = pivalate, M = Co, 1; M = Ni, 2), with a coordination configuration at the intermediate between an octahedron and a trigonal prism, are reported. Direct current magnetic data and high-frequency and -field EPR spectra (HFEPR) of 1 have been modeled by a general Hamiltonian considering the first-order orbital angular momentum, while the spin Hamiltonian was used to interpret the data of 2. Both 1 and 2 show easy-axis magnetic anisotropies, which are further supported by ab initio calculations. Alternating current (ac) magnetic susceptibilities reveal slow magnetic relaxation at an applied dc field of 0.1 T in 1, which is characteristic of a field-induced single-ion magnet (SIM), but 2 does not exhibit single-ion magnetic properties at 1.8 K. Detailed analyses of relaxation times show a dominant contribution of a Raman process for spin relaxation in 1.

Unusual rearrangement of an N-heterocyclic carbene via a ring-opening and ring-closing process.

The reaction of a pentadentate NHC ligand precursor with Ni(OAc)2·4H2O or Pd(OAc)2 in the presence of a base yields four-coordinate square-planar Ni(ii) and Pd(ii) complexes with an unusual ligand generated in situ. A series of experimental studies point to a ring-opening and ring-closing process via novel C-N bond cleavage and formation.

Charge and Bonding in CuGeO3 Nanorods.

We combine infrared and Raman spectroscopies to investigate finite length scale effects in CuGeO3 nanorods. The infrared-active phonons display remarkably strong size dependence whereas the Raman-active features are, by comparison, nearly rigid. A splitting analysis of the Davydov pairs reveals complex changes in chemical bonding with rod length and temperature. Near the spin-Peierls transition, stronger intralayer bonding in the smallest rods indicates a more rigid lattice which helps to suppress the spin-Peierls transition. Taken together, these findings advance the understanding of size effects and collective phase transitions in low-dimensional oxides.

Synthesis, structures and luminescence properties of amine-bis(N-heterocyclic carbene) copper(i) and silver(i) complexes.

A series of Ag(i) and Cu(i) complexes [Ag3(L1)2][PF6]3 (8), [Ag3(L2)2][PF6]3 (9), [Cu(L1)][PF6] (10) and [Cu(L2)][PF6] (11) have been synthesized by reactions of the tridentate amine-bis(N-heterocyclic carbene) ligand precursors [H2L1][PF6]2 (6) and [H2L2][PF6]2 (7) with Ag2O and Cu2O, respectively. Complexes 10 and 11 can also be obtained by transmetalation of 8 and 9, respectively, with 3.0 equiv. of CuCl. A heterometallic Cu/Ag-NHC complex [Cu2Ag(L1)2(CH3CN)2][PF6]3 (12) is formed by the reaction of 8 with 2.0 equiv. of CuCl. All complexes have been characterized by NMR, electrospray ionization mass spectrometry (ESI-MS), and single-crystal X-ray diffraction studies. The luminescence properties of 10-12 in solution and the solid state have been studied. At room temperature, 10-12 exhibit evident luminescence in solution and the solid state. The emission wavelengths are found to be identical at 483 nm in CH3CN, but they are 484, 480 and 592 nm in the solid state for 10-12, respectively. These results suggest that 12 dissociates into two molecules of 10 and Ag(i) ions in solution. Complex 12 is the first luminescent heterometallic Cu/Ag-NHC complex.