The Exception That Proves the Rule: How Sodium Chelation Can Alter the Charge-Cell Binding Correlation of Fluorescein-Based Multimodal Imaging Agents.

In the present study we describe and explain an aberrant behavior in terms of receptor binding profile of a fluorescein-based multimodal imaging agent for gastrin releasing peptide receptor (GRPR) visualization by elucidating a chelating mechanism on sodium ions of its fluorescent dye moiety. This hypothesis is supported by both biological results and spectroscopic analyses of different fluorescein-carrying conjugates and an equally charged set of analogous tartrazine-based GRPR-binding imaging agents. Fluorescein interacts with sodium which reduces the overall negative charge of the dye molecule by one. This reduction in apparent total net charge explains the exceptional behavior found for the fluorescein-based multimodal bioconjugate in the context of the charge-cell binding correlation hypothesis.

Side-by-Side Comparison of Five Chelators for 89Zr-Labeling of Biomolecules: Investigation of Chemical/Radiochemical Properties and Complex Stability.

In this work, five different chelating agents, namely DFO, CTH-36, DFO*, 3,4,3-(LI-1,2-HOPO) and DOTA-GA, were compared with regard to the relative kinetic inertness of their corresponding 89Zr complexes to evaluate their potential for in vivo application and stable 89Zr complexation. The chelators were identically functionalized with tetrazines, enabling a fully comparable, efficient, chemoselective and biorthogonal conjugation chemistry for the modification of any complementarily derivatized biomolecules of interest. A small model peptide of clinical relevance (TCO-c(RGDfK)) was derivatized via iEDDA click reaction with the developed chelating agents (TCO = trans-cyclooctene and iEDDA = inverse electron demand Diels-Alder). The bioconjugates were labeled with 89Zr4+, and their radiochemical properties (labeling conditions and efficiency), logD(7.4), as well as the relative kinetic inertness of the formed complexes, were compared. Furthermore, density functional theory (DFT) calculations were conducted to identify potential influences of chelator modification on complex formation and geometry. The results of the DFT studies showed-apart from the DOTA-GA derivative-no significant influence of chelator backbone functionalization or the conjugation of the chelator tetrazines by iEDDA. All tetrazines could be efficiently introduced into c(RGDfK), demonstrating the high suitability of the agents for efficient and chemoselective bioconjugation. The DFO-, CTH-36- and DFO*-modified c(RGDfK) peptides showed a high radiolabeling efficiency under mild reaction conditions and complete 89Zr incorporation within 1 h, yielding the 89Zr-labeled analogs as homogenous products. In contrast, 3,4,3-(LI-1,2-HOPO)-c(RGDfK) required considerably prolonged reaction times of 5 h for complete radiometal incorporation and yielded several different 89Zr-labeled species. The labeling of the DOTA-GA-modified peptide was not successful at all. Compared to [89Zr]Zr-DFO-, [89Zr]Zr-CTH-36- and [89Zr]Zr-DFO*-c(RGDfK), the corresponding [89Zr]Zr-3,4,3-(LI-1,2-HOPO) peptide showed a strongly increased lipophilicity. Finally, the relative stability of the 89Zr complexes against the EDTA challenge was investigated. The [89Zr]Zr-DFO complex showed-as expected-a low kinetic inertness. Unexpectedly, also, the [89Zr]Zr-CTH-36 complex demonstrated a high susceptibility against the challenge, limiting the usefulness of CTH-36 for stable 89Zr complexation. Only the [89Zr]Zr-DFO* and the [89Zr]Zr-3,4,3-(LI-1,2-HOPO) complexes demonstrated a high inertness, qualifying them for further comparative in vivo investigation to determine the most appropriate alternative to DFO for clinical application.

Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge-Cell Binding Correlation.

In the context of hybrid multimodal imaging agents for gastrin releasing peptide receptor (GRPR) targeting, a correlation between the net charge and the receptor affinity of the agents was recently found. In particular, a decrease in in vitro GRPR binding affinity was observed in case of an increasing number of negative charges for dually labeled GRPR-specific peptide dimers suited for positron emission tomography and optical imaging (PET/OI). This adverse influence of anionic charges could be in part compensated by a higher valency of peptide multimerization. However, it remains unknown whether this adverse effect of anionic charges is limited to peptide multimers or if it is also found or even more pronounced when GRPR-specific peptide monomers are dually labeled with fluorescent dye and chelating agent/radionuclide. Moreover, it would be important to know if this effect is limited to GRPR-specific agents only or if these observations also apply to other dually labeled peptides binding to other receptor types. To address these questions, we synthesized hybrid labels, comprising a chelator, different fluorescent dyes carrying different net charges and a functional group for bioconjugation and introduced them into different peptides, specifically targeting the GRPR, the melanocortin-1 receptor (MC1R) and integrin αvß3. The synthesized conjugates were evaluated with regard to their chemical, radiochemical, photophysical and receptor affinity properties. It was found that neither the 68Ga-radiolabeling nor the fluorescence characteristics of the dyes were altered by the conjugation of the MIUs to the peptides. Further, it was confirmed that the net number of anionic charges has a negative effect on the GRPR-binding affinity of the GRPR-targeting MIU-peptide monomer conjugates and that this same effect was also found to the same extent for the other receptor systems studied.

Are heterobivalent GRPR- and VPAC1R-bispecific radiopeptides suitable for efficient in vivo tumor imaging of prostate carcinomas?

Receptor-specific peptides labeled with positron emitters play an important role in the clinical imaging of several malignancies by positron emission tomography (PET). Radiolabeled heterobivalent bispecific peptidic ligands (HBPLs) can target more than one receptor type and by this - besides exhibiting other advantages - increase tumor imaging sensitivity. In the present study, we show the initial in vivo evaluation of the most potent heterobivalent gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC1R)-bispecific radiotracer and determined its tumor visualization potential via PET/CT imaging. For this purpose, the most potent described HBPL was synthesized together with its partly scrambled heterobivalent monospecific homologs and its monovalent counterparts. The agents were efficiently labeled with 68Ga3+ and evaluated in an initial PET/CT tumor imaging study in a human prostate carcinoma (PCa) xenograft rat tumor model established for this purpose. None of the three 68Ga-HBPLs enabled a clear tumor visualization and a considerably higher involvement in receptor-mediated uptake was found for the GRPR-binding part of the molecule than for the VPAC1R-binding one. Of the monovalent radiotracers, only [68Ga]Ga-NODA-GA-PESIN could efficiently delineate the tumor, confirming the results. Thus, this work sets the direction for future developments in the field of GRPR- and VPAC1R-bispecific radioligands, which should be based on other VPAC1R-specific peptides than PACAP-27.

PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study.

Recently, anionic charges were found to negatively influence the in vitro gastrin-releasing peptide receptor (GRPR) binding parameters of dually radioisotope and fluorescent dye labeled GRPR-specific peptide dimers. From this, the question arose if this adverse impact on in vitro GRP receptor affinities could be mitigated by a higher valency of peptide multimerization. For this purpose, we designed two different hybrid multimodal imaging units (MIUs), comprising either one or two click chemistry-compatible functional groups and reacted them with PESIN (PEG3-BBN7-14, PEG = polyethylene glycol) dimers to obtain a dually labeled peptide homodimer or homotetramer. Using this approach, other dually labeled peptide monomers, dimers, and tetramers can also be obtained, and the chelator and fluorescent dye can be adapted to specific requirements. The MIUs, as well as their peptidic conjugates, were evaluated in terms of their photophysical properties, radiolabeling efficiency with 68Ga and 64Cu, hydrophilicity, and achievable GRP receptor affinities. Here, the hydrophilicity and the GRP receptor binding affinities were found to be especially strongly influenced by the number of negative charges and peptide copies, showing logD (1-octanol-water-distribution coefficient) and IC50 (half maximal inhibitory concentration) values of -2.2 ± 0.1 and 59.1 ± 1.5 nM for the homodimer, and -1.9 ± 0.1 and 99.8 ± 3.2 nM for the homotetramer, respectively. From the obtained data, it can be concluded that the adverse influence of negatively charged building blocks on the in vitro GRP receptor binding properties of dually labeled PESIN multimers can, at least partly, be compensated for by the number of introduced peptide binding motives and the used molecular design.

Design, Synthesis, In Vitro and In Vivo Evaluation of Heterobivalent SiFAlin-Modified Peptidic Radioligands Targeting Both Integrin αvß3 and the MC1 Receptor-Suitable for the Specific Visualization of Melanomas?

Combining two peptides addressing two different receptors to a heterobivalent peptidic ligand (HBPL) is thought to enable an improved tumor-targeting sensitivity and thus tumor visualization, compared to monovalent peptide ligands. In the case of melanoma, the Melanocortin-1 receptor (MC1R), which is stably overexpressed in the majority of primary malignant melanomas, and integrin αvß3, which is involved in lymph node metastasis and therefore has an important role in the transition from local to metastatic disease, are important target receptors. Thus, if a radiolabeled HBPL could be developed that was able to bind to both receptor types, the early diagnosis and correct staging of the disease would be significantly increased. Here, we report on the design, synthesis, radiolabeling and in vitro and in vivo testing of different SiFAlin-modified HBPLs (SiFA = silicon fluoride acceptor), consisting of an MC1R-targeting (GG-Nle-c(DHfRWK)) and an integrin αvß3-affine peptide (c(RGDfK)), being connected by a symmetrically branching framework including linkers of differing length and composition. Kit-like 18F-radiolabeling of the HBPLs 1-6 provided the labeled products [18F]1-[18F]6 in radiochemical yields of 27-50%, radiochemical purities of ≥95% and non-optimized molar activities of 17-51 GBq/µmol within short preparation times of 25 min. Besides the evaluation of radiotracers regarding logD(7.4) and stability in human serum, the receptor affinities of the HBPLs were investigated in vitro on cell lines overexpressing integrin αvß3 (U87MG cells) or the MC1R (B16F10). Based on these results, the most promising compounds [18F]2, showing the highest affinity to both target receptors (IC50 (B16F10) = 0.99 ± 0.11 nM, IC50 (U87MG) = 1300 ± 288 nM), and [18F]4, exhibiting the highest hydrophilicity (logD(7.4) = -1.39 ± 0.03), were further investigated in vivo and ex vivo in a xenograft mouse model bearing both tumors. For both HBPLs, clear visualization of B16F10, as well as U87MG tumors, was feasible. Blocking studies using the respective monospecific peptides demonstrated both peptide binders of the HBPLs contributing to tumor uptake. Despite the somewhat lower target receptor affinities (IC50 (B16F10) = 6.00 ± 0.47 nM and IC50 (U87MG) = 2034 ± 323 nM) of [18F]4, the tracer showed higher absolute tumor uptakes ([18F]4: 2.58 ± 0.86% ID/g in B16F10 tumors and 3.92 ± 1.31% ID/g in U87MG tumors; [18F]2: 2.32 ± 0.49% ID/g in B16F10 tumors and 2.33 ± 0.46% ID/g in U87MG tumors) as well as higher tumor-to-background ratios than [18F]2. Thus, [18F]4 demonstrates to be a highly potent radiotracer for the sensitive and bispecific imaging of malignant melanoma by PET/CT imaging and impressively illustrates the suitability of the underlying concept to develop heterobivalent integrin αvß3- and MC1R-bispecific radioligands for the sensitive and specific imaging of malignant melanoma by PET/CT.

Gapped magnetic ground state in quantum spin liquid candidate κ-(BEDT-TTF)2Cu2(CN)3.

Geometrical frustration, quantum entanglement, and disorder may prevent long-range ordering of localized spins with strong exchange interactions, resulting in an exotic state of matter. κ-(BEDT-TTF)2Cu2(CN)3 is considered the prime candidate for this elusive quantum spin liquid state, but its ground-state properties remain puzzling. We present a multifrequency electron spin resonance (ESR) study down to millikelvin temperatures, revealing a rapid drop of the spin susceptibility at 6 kelvin. This opening of a spin gap, accompanied by structural modifications, is consistent with the formation of a valence bond solid ground state. We identify an impurity contribution to the ESR response that becomes dominant when the intrinsic spins form singlets. Probing the electrons directly manifests the pivotal role of defects for the low-energy properties of quantum spin systems without magnetic order.

Synthesis, characterization and optimization of in vitro properties of NIR-fluorescent cyclic α-MSH peptides for melanoma imaging.

Melanoma are malignant tumors derived from melanocytes being responsible for the majority of skin cancer deaths with an increasing rate of incidence. The Melanocortin-1 receptor (MC1R) has been recognized as a molecular target for melanoma detection. Here, we report on the development and optimization of molecular probes which are based on novel conjugates of near-infrared (NIR) fluorescent indocyanine dyes and an MC1R-targeting peptide intended for optical fluorescence imaging enabling an early, specific, accurate and sensitive diagnosis of malignant melanomas. The introduction of anionic groups into the aromatic ring of the indolenine substructure of the conjugated dyes has shown to result in a strong fluorescence in aqueous solution and a concomitant increase of binding affinities of the peptide conjugates to the target receptor. The length and flexibility of the PEG chain introduced as a linker, as well as the nature of its attachment to the dye also affect the binding affinities, albeit to a lower extent. The conjugates have been successfully applied in the MC1R-specific staining of B16F10 melanoma cells, both in cell cultures and in microtome sections of solid tumors.

Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye.

The development of hybrid multimodal imaging synthons (MIS), carrying in addition to a chelator for radiometal labeling also a near-infrared (NIR) fluorescent cyanine dye was the aim of this work. The MIS should be introducible into biomolecules of choice via an efficient and chemoselective click chemistry reaction. After chemical optimization, a successful synthetic strategy towards such hybrid MIS was developed, based on solid phase-based synthesis techniques and applying different near-infrared fluorescent cyanine dyes. The developed hybrid agents were shown to be easily introducible into a model homobivalent peptidic gastrin-releasing peptide receptor- (GRPR)-specific carrier without forming any side products and the MIS as well as their bioconjugates were radiolabeled with the positron-emitter 68Ga3+. The hybrid multimodal agents were characterized with regard to their logDs, GRPR target affinities and photophysical characteristics. It could be shown that the properties of the bioconjugates were not per se affected by the introduction of the MIS but that the cyanine dye used and specifically the number of comprised negative charges per dye molecule can have a considerable influence on target receptor binding. Thus, the molecular toolbox described here enables the synthesis of tailored hybrid multimodal imaging synthons for biomolecule modification, meeting the specific need and envisioned application of the combined imaging agent.

Functional Hybrid Molecules for the Visualization of Cancer: PESIN-Homodimers Combined with Multimodal Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging: Suited for Tracking of GRPR-Positive Malignant Tissue*.

We describe multimodal imaging probes for gastrin-releasing peptide receptor (GRPR)-specific targeting suited for positron emission tomography and optical imaging (PET/OI), consisting of PESIN (PEG3 -BBN7-14 ) dimers connected to multimodal imaging subunits. These multimodal agents comprise a fluorescent dye for OI and the chelator ((1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid) (NODA-GA) for PET radiometal isotope labelling. Special focus was put on the influence of the used dyes on the properties of the whole bioconjugates. For this, several compounds with different fluorescent dyes and non-dye carrying subunits were synthesized and investigated. As fluorescent dyes, dansyl, NBD, derivatives of fluorescein, coumarin and rhodamine as well as three pyrilium-based dyes were employed. Considerable influence of the charge of the colored unit on hydrophilicity as well as in vitro target receptor binding was observed and classified. High radiochemical yields and purities were found during radiolabeling of the multimodal imaging subunits as well as their GRPR-specific bioconjugates with 68 Ga. Examinations of the photophysical properties of both molecule species displayed no loss or alteration of fluorescence characteristics.

Probing two PESIN-indocyanine-dye-conjugates: significance of the used fluorophore.

Peptide-dye-conjugates hold a great promise in application for biological and medical imaging of cellular processes and in delineation and characterization of human tumors. In particular, indocyanine dyes are of great interest due to their reported superior properties such as absorption and emission in the near-infrared (NIR) spectral range, favorable Stokes shifts and their well-studied safety profile in humans. In this study, we investigated and describe the influence of indocyanine dyes on different properties of the final peptide-dye-conjugates. As a target peptide, PESIN, a bombesin derivative, was used as a model peptide which addresses GRP receptors overexpressed on different malignancies. Here, we map similarities and differences of the fluorescent conjugates and by this elucidate the influence of the dyes on different properties of the formed conjugates. We performed the dye syntheses, subsequent bioconjugation reactions and in the following investigated the optical properties, water/octanol distribution coefficients and target receptor affinities by in vitro competitive binding studies on PC-3 cells. The obtained results give a handrail to medical and biological researchers planning studies involving indocyanine dye biomolecule conjugates.

The metal-insulator transition in the organic conductor ß″-(BEDT-TTF)2Hg(SCN)2Cl.

We explore the nature of the metal-insulator transition in the two-dimensional organic compound ß″-(BEDT-TTF)2Hg(SCN)2Cl by x-ray, electrical transport, ESR, Raman, and infrared investigations. Magnetic and vibrational spectroscopy concurrently reveal a gradual dimerization along the stacking direction (a-b), setting in already at the crossover temperature of 150 K from the metallic to the insulating state. A spin gap of Δσ=47 meV is extracted. From the activated resistivity behavior below T = 55 K, a charge gap of Δρ=60 meV is derived. At TCO = 72 K, the C=C vibrational modes reveal the development of a charge-ordered state with a charge disproportionation of 2δρ=0.34e. In addition to a slight structural dimerization, charge-order causes stripes most likely perpendicular to the stacks.

Photoswitchable stable charge-distributed states in a new cobalt complex exhibiting photo-induced valence tautomerism.

We report the synthesis and magnetic and photomagnetic behaviour of a novel valence tautomeric cobalt complex, [Co(3,5-dbbq)2(µ-bpym)] (1) (3,5-dbbq = 3,5-di-tert-butyl-1,2-benzoquinone and µ-bpym = 2,2'-bipyrimidine). The synthesis is performed by reacting Co2(CO)8 and µ-bpym in the presence of the ligand 3,5-dbbq in a mixed solvent under inert atmosphere. The magnetic behavior clearly shows the presence of electron transfer from the catecholate ligand to the cobalt center, producing valence tautomers of [Co(II)(SQ)2] with a transition temperature (T1/2) of 215 K. Photomagnetic studies, performed via both SQUID magnetometry and X-band electron paramagnetic resonance, show the clear presence of photoinduced valence tautomerism, at temperatures considerably higher than previous systems. A metastable charge distribution is observed, strengthening previous investigations on the character of mixed valence ligands. Entropy-driven valence tautomeric interconversion is observed, and drives the transition to the most stable charge distribution. The complex has the ability to coordinate and can be used as a photoswitchable building block, with the photomagnetic characterisation evidencing a metastable state lifetime of the photo-induced valence tautomeric process of ca. 2.9 × 10(4) s below 20 K. The observed yields are higher than ones in similar systems, showing that tiny changes in the molecular structures may have a huge impact.

UV-vis-NIR and EPR characterisation of the redox series [MQ(3)](2+,+,0,-,2-), M = Ru or Os, and Q = o-quinone derivative.

The neutral title compounds with Q = 3,5-di-tert-butyl-o-quinone or 4,6-di-tert-butyl-N-phenyl-o-iminobenzoquinone (Q(x)) were studied by UV-vis-NIR spectroelectrochemistry and by EPR spectroscopy in the case of the odd-electron monocation and monoanion intermediates. Supported by DFT and TD-DFT calculations, the results indicate stepwise electron removal from predominantly ligand-based delocalised MOs on oxidation whereas the stepwise electron uptake on reduction involves unoccupied MOs with considerably metal-ligand mixed character. In both cases, the strong near-infrared absorption of the neutral precursors diminishes. In comparison to the ruthenium series, the osmium analogues exhibit larger transition energies from enhanced MO splitting and a different EPR response due to the higher spin-orbit coupling. The main difference between the quinone (1(n), 2(n)) and corresponding monoiminoquinone systems (3(n), 4(n)) is the shift of about 0.6 V to lower potentials for the monoimino analogues. While the absorption features do not differ markedly, the EPR data reflect a higher degree of covalent bonding for the complexes with monoimino ligands.

Filling gaps in the series of noninnocent hetero-1,3-diene chelate ligands: ruthenium complexes of redox-active α-azocarbonyl and α-azothiocarbonyl ligands RNNC(R')E, E = O or S.

The series of 4-center unsaturated chelate ligands A═B-C═D with redox activity to yield (-)A-B═C-D(-) in two steps has been complemented by two new combinations RNNC(R')E, E = O or S, R = R' = Ph. The ligands N-benzoyl-N'-phenyldiazene = L(O), and N-thiobenzoyl-N'-phenyldiazene = L(S), (obtained in situ) form structurally characterized compounds [(acac)(2)Ru(L)], 1 with L = L(O), and 3 with L = L(S), and [(bpy)(2)Ru(L)](PF(6)), 2(PF(6)) with L = L(O), and 4(PF(6)) with L = L(S) (acac(-) = 2,4-pentanedionato; bpy = 2,2'-bipyridine). According to spectroscopy and the N-N distances around 1.35 Å and N-C bond lengths of about 1.33 Å, all complexes involve the monoanionic (radical) ligand form. For 1 and 3, the antiferromagnetic spin-spin coupling with electron transfer-generated Ru(III) leads to diamagnetic ground states of the neutral complexes, whereas the cations 2(+) and 4(+) are EPR-active radical ligand complexes of Ru(II). The complexes are reduced and oxidized in reversible one-electron steps. Electron paramagnetic resonance (EPR) and UV-vis-NIR spectroelectrochemistry in conjunction with time-dependent density functional theory (TD-DFT) calculations allowed us to assign the electronic transitions in the redox series, revealing mostly ligand-centered electron transfer: [(acac)(2)Ru(III)(L(0))](+) ⇌ [(acac)(2)Ru(III)(L(•-))] ⇌ [(acac)(2)Ru(III)(L(2-))](-)/[(acac)(2)Ru(II)(L(•-))](-), and [(bpy)(2)Ru(III)(L(•-))](2+)/[(bpy)(2)Ru(II)(L(0))](2+) ⇌ [(bpy)(2)Ru(II)(L(•-))](+) ⇌ [(bpy)(2)Ru(II)(L(2-))](0). The differences between the O and S containing compounds are rather small in comparison to the effects of the ancillary ligands, acac(-) versus bpy.

Spectroelectrochemical evidence for the nitrosyl redox siblings NO+, NO*, and NO- coordinated to a strongly electron-accepting Fe(II) porphyrin: DFT calculations suggest the presence of high-spin states after reduction of the Fe(II)-NO- complex.

Experimental and computational results for the electron-deficient porphyrin complex [Fe(NO)(TFPPBr(8))] (1; TFPPBr(8)=2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(pentafluorophenyl)porphyrin) are reported with respect to its electron-transfer behavior. Complex 1 undergoes three one-electron processes: two reversible reductions and one irreversible oxidation. Spectroelectrochemical measurements (IR and UV/Vis/NIR spectroscopy) of (14)NO- and (15)NO-containing material indicate that the first reduction to 1(-) occurs largely on the NO ligand to produce nitroxyl anion (NO(-)) character, as evident from the considerable change in ν(NO) from 1715 to around 1550 cm(-1). The second reduction to 1(2)(-) does not result in a further shift of ν(NO) to lower frequencies, but to a surprising high-energy shift to 1590 cm(-1). This and the notable changes of the characteristic porphyrin vibrations as well as significant changes of the UV/Vis absorptions indicate a porphyrin-centered process; DFT calculations predict the shift of ν(NO) to higher frequencies for the intermediate- and high-spin states of 1(2-). The oxidation of 1 is irreversible on the voltammetry timescale, but chemically reversible in spectroelectrochemical experiments, suggesting that the cationic form dissociates to the corresponding ferric porphyrin and NO. DFT calculations support the interpretation of the experimental results.

First structurally characterized mono- and dinuclear ruthenium complexes derived from zwitterionic quinonoid ligands.

Electron transfer and delocalization of the pi systems were investigated in mono- and dinuclear Ru complexes with the zwitterionic ligand L = N,N'-diisopropyl-2-amino-5-alcoholate-1,4-benzoquinonemonoiminium.

Combining two non-innocent ligands in isomeric complexes [Pt(pap)(m)Q(n)](0) (pap = phenylazopyridine, Q = 3,5-di-tert-butyl-benzoquinone.

Isomeric complexes of platinum, which contain two non-innocent ligands are reported. The built-in coordination asymmetry in the ligands makes it possible to separate two different positional isomers. Results from X-ray crystallography is used to invoke the popular structure oxidation state correlation in these complexes. The redox processes are discussed and interpreted with the help of UV-vis-NIR and EPR spectroelectrochemistry.