Preparation, X-ray Characterization, and Reactivity of the Rod-like and Angular Germanium- and Titanium(IV)-Capped Iron(II) Bis-Clathrochelates and Their Mono- and Bis-Capped (Semi)clathrochelate Precursors.

Transmetalation of the bis{triethylantimony(V)}-capped iron(II) tris-α-dioximate with n-butylboronic acid afforded the mixed antimony, boron cross-linked clathrochelate with single reactive antimony(V)-based apical fragment. This macrobicyclic precursor easily underwent the transmetalation reactions with germanium and titanium(IV) alkoxides to give the rod-like and angular FeII2MIV-trinuclear bis-clathrochelates. Those of the aforementioned diantimony(V)-capped complex with 3- and 4-carboxyphenylboronic acids afforded the monoboron-capped iron(II) semiclathrochelates, undergoing a double-cyclization (macrobicyclization) with germanium- and titanium(IV)-based capping agents. The reactions in the low-temperature range unexpectedly gave the stable 2:1 associates, formed by the bridging of two carboxyl-terminated macrobicyclic molecules of the mixed carboxylboron, triethylantimony-capped iron(II) clathrochelate with a triethylantimony(V)-based linker fragment. The obtained complexes were characterized using elemental analysis, MALDI-TOF, 1H and 13C{1H} NMR and UV-vis spectra, and single-crystal XRD experiments. The encapsulated iron(II) ion in their 3D-molecules is situated almost in the center of its FeN6-coordination polyhedron possessing a truncated trigonal-pyramidal geometry. Fe-N distances fall in the range 1.887(7)-1.945(4) Å characteristic of the low-spin iron(II) complexes. The cross-linking titanium and germanium(IV) ions in the corresponding bis-clathrochelate molecules form the octahedral MIVO6-coordination polyhedra, the MIV-O distances of which vary from 1.946(2) to 1.964(2) Å and from 1.879(7) to 1.907(6) Å, respectively.

Effects of solvatomorphism, the nature of a chelating ligand synthon and a counterion on the single crystal XRD structure and SMM properties of paramagnetic monocapped cobalt(II) tris-pyrazoloximates.

A series of monocapped cobalt(II) tris-pyrazoloximates was obtained through the template condensation of the corresponding pyrazoloxime, phenylboronic acid and a suitable cobalt(II) halogenide. Comparing 3-acetylpyrazoloxime versus its methine-containing homolog, the former produced cobalt(II) clathrochelates in substantially higher yields due to the electron donating effect of the methyl substituent, increasing the N-donor ability of its oxime group. Their less N-donor analog with the electron acceptor trifluoromethyl group did not form cobalt(II) complexes of this type. In all their solvent-free and solvent-containing crystals, the encapsulated cobalt(II) ion adopted a high-spin state, as gauged by the Co-N bond lengths of 2.112(4)-2.188(9) Å, and was located almost in the center of its CoN6-coordination polyhedron. Their CoN6-polyhedra had an almost ideal trigonal-prismatic (TP) geometry with distortion angles φ below 4°. This TP-like geometry was assisted by hydrogen bonding between their NH groups and the apical counterion. The absence of methyl groups makes them close to an ideal TP. In contrast, stronger N-H⋯Cl hydrogen bonds occurred in the methyl-containing complex, while the Co-N bond lengths stayed the same at 2.144(2) Å on average. In its solvates with benzene, chloroform and acetone, there is a clear tendency for φ to decrease from 2.7(3)° to 0.47(13)°. The comparable effects of the ribbed methyl substituents, the cross-linking counterion and the lattice solvent on their molecular geometry were observed; the larger the distortions from an ideal TP geometry, the stronger the hydrogen bonds to the corresponding apical halogenide anion. The analysis of the experimental AC- and DC-magnetometry data for their fine-crystalline samples suggests that the passing from the derivative of the methyl-substituted synthon to that of its methine-containing homolog caused a substantial decrease in the magnetic susceptibility value χT and an increase in the QTM contribution to the magnetic relaxation. The effect of a cross-linking halogenide counteranion on the Orbach remagnetization barrier is greater than that of the solvatomorphism of their crystals.

Precise Fingerprint Determination of Vibrational Infrared Spectra in a Series of Co(II) Clathrochelates through Experimental and Theoretical Analyses.

The energetic demands of modern society for clean energy vectors, such as H2, have caused a surge in research associated with homogeneous and immobilized electrocatalysts that may replace Pt. In particular, clathrochelates have shown excellent electrocatalytic properties for the hydrogen evolution reaction (HER). However, the actual mechanism for the HER catalyzed by these d-metal complexes remains an open debate, which may be addressed via Operando spectroelectrochemistry. The prediction of electrochemical properties via density functional theory (DFT) needs access to thermodynamic functions, which are only available after Hessian calculations. Unfortunately, there is a notable lack in the current literature regarding the precise evaluation of vibrational spectra of such complexes, given their structural complexity and the associated tangled IR spectra. In this work, we have performed a detailed theoretical and experimental analysis in a family of Co(II) clathrochelates, in order to establish univocally their IR pattern, and also the calculation methodology that is adequate for such predictions. In summary, we have observed the presence of multiple common bands shared by this clathrochelate family, using the B3LYP functional, the LANL2DZ basis, and effective core potentials (ECP) for heavy atoms. The most important issue addressed in this article was therefore related to the detailed assignment of the fingerprint associated with cobalt(II) clathrochelates, which is a challenging endeavor due to the crowded nature of their spectra.

3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo.

The amount of unfolded proteins is increased in cancer cells, leading to endoplasmic reticulum (ER) stress. Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt's lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).

57Fe Mössbauer and DFT study of the electronic and spatial structures of the iron(II) (pseudo)clathrochelates: the effect of ligand field strength.

Combined experimental 57Fe Mössbauer and theoretical DFT study of a series of iron(II)-centered (pseudo)macrobicyclic analogs and homologs was performed. The field strength of the corresponding (pseudo)encapsulating ligand was found to affect both the spin state of a caged iron(II) ion and the electron density at its nucleus. In a row of the iron(II) tris-dioximates, passing from the non-macrocyclic complex to its monocapped pseudomacrobicyclic analog caused an increase both in the ligand field strength and in the electron density at the Fe2+ ion, and, therefore, a decrease in the isomer shift (IS) value (so-called "semiclathrochelate effect"). Its macrobicyclization, giving the quasiaromatic cage complex, caused a further increase in the two former parameters and a decrease in IS (so-called "macrobicyclic effect"). The trend of their IS values was successfully predicted using the performed quantum-chemical calculations and the corresponding linear correlation with the electron density at their 57Fe nuclei was plotted. A variety of different functionals can be successfully used for such excellent prediction. The slope of this correlation was found to be unaffected by the used functional. In contrast, the predictions of both the sign and the values of quadrupole splitting (QS) for them, based on the theoretical calculations of EFG tensors, were found to be a real great challenge, which could not be solved at the moment even in the case of these C3-pseudosymmetric iron(II) complexes with known XRD structures. The latter experimental data allowed us to deduce a sign of the QSs for them. The straightforwarded molecular design of a (pseudo)encapsulating ligand is proposed to control both the spin state and the redox characteristics of an encapsulated metal ion.

Multistep synthesis and X-ray structures of carboxyl-terminated hybrid iron(II) phthalocyaninatoclathrochelates and their postsynthetic transformation into polytopic carboranyl-containing derivatives.

A multistep general synthetic strategy towards polytopic carboranyl-containing (semi)clathrochelate metal complexes, based on the template synthesis, transmetallation, amide condensation and 1,3-dipolar cycloaddition reactions, is developed. Their mono(semi)clathrochelate precursors with a single reactive group were obtained using a transmetallation of the triethylantimony-capped macrobicyclic precursor. The thus obtained carboxyl-terminated iron(II) semiclathrochelate underwent a macrobicyclization with zirconium(IV) phthalocyaninate to form the corresponding phthalocyaninatoclathrochelate. The direct one-pot template condensation of the suitable chelating and cross-linking ligand synthons on the Fe2+ ion as a matrix was also used for its preparation. Further amide condensation of the aforementioned semiclathrochelate and hybrid complexes with propargylamine in the presence of carbonyldiimidazole gave the (pseudo)cage derivatives with a terminal CC bond. Their "click" reaction with an appropriate carboranylmethyl azide afforded the ditopic carboranosemiclathrochelates and the tritopic carboranyl-containing phthalocyaninatoclathrochelates with a flexible spacer fragment between their polyhedral entities. The obtained new complexes were characterized using elemental analysis, MALDI-TOF mass spectrometry, multinuclear NMR, and UV-vis spectroscopy, and by single crystal X-ray diffraction experiments. Their FeN6-coordination polyhedra show a truncated trigonal-pyramidal geometry, while the cross-linking heptacoordinate Zr4+ or Hf4+ cations in the hybrid compounds form the MIVN4O3-coordination polyhedra with the geometry of a capped trigonal prism.

Synthesis, X-ray structure and magnetic properties of the apically functionalized monocapped cobalt(II) tris-pyridineoximates possessing SMM behaviour.

The title cobalt(II) pseudoclathrochelate complexes possess an intermediate trigonal prismatic-trigonal antiprismatic geometry. As follows from PPMS data, they exhibit an SMM behaviour with Orbach relaxation barriers of approximately 90 K. Paramagnetic NMR experiments confirmed a persistence of these magnetic characteristics in solution. Therefore, a straightforward apical functionalization of this 3D molecular platform for its targeted delivery to a given biosystem can be performed without substantial changes.

Synthesis, crystal polymorphism and spin crossover behavior of adamantylboron-capped cobalt(II) hexachloroclathrochelate and its transformation into the CoIIICoIICoIII-bis-macrobicyclic derivative.

Fast crystallization of the monoclathrochelate cobalt(II) intracomplex [Co(Cl2Gm)3(BAd)2] (where Cl2Gm2- is a dichloroglyoxime dianion and BAd is an adamantylboron capping group, 1), initially obtained by the direct template condensation of the corresponding chelating α-dioximate and cross-linking ligand synthons on the Co2+ ion as a matrix, from benzene or dichloromethane afforded its structural triclinic and hexagonal polymorphs. Its prolonged recrystallization from dichloromethane under air atmosphere and sunlight irradiation unexpectedly gave the crystals of the CoIIICoIICoIII-trinuclear dodecachloro-bis-clathrochelate intracomplex [[CoIII(Cl2Gm)3(BAd)]2CoII] (2), the molecule of which consists of two macrobicyclic frameworks with encapsulated low-spin (LS) Co3+ ions, which are cross-linked by a µ3-bridging Co2+ ion as a bifunctional Lewis-acidic center. The most plausible pathway of such a 1 → 2 transformation is based on the photoinitiated radical oxidation of dichloromethane with air oxygen giving the reactive species. Cobalt(II) monoclathrochelate 1 was found to undergo a temperature-induced spin crossover (SCO) both in its solutions and in the solid state. In spite of the conformational rigidity of the corresponding quasiaromatic diboron-capped tris-α-dioximate framework, the main parameters of this SCO transition (i.e., its completeness and gradual character) are strongly affected by the nature of the used solvent (in the case of its solutions) and by the structural polymorphism of its crystals (in the solid state). In the latter case, the LS state (S = 1/2) of this complex is more thermally stable and, therefore, the cobalt(II)-centered 1/2 → 3/2 SCO is more gradual than that in solutions.

Hybrid iron(II) phthalocyaninatoclathrochelates with a terminal reactive vinyl group and their organo-inorganic polymeric derivatives: synthetic approaches, X-ray structures and copolymerization with styrene.

Hybrid metallo(IV)phthalocyaninate-capped tris-dioximate iron(II) complexes (termed as "phthalocyaninatoclathrochelates") with non-equivalent apical fragments and functionalized with one terminal reactive vinyl group were prepared for the first time using three different synthetic approaches: (i) transmetallation (capping group exchange) of the appropriate labile boron,antimony-capped cage precursors, (ii) capping of the initially isolated reactive semiclathrochelate intermediate, and (iii) direct one-pot template condensation of their ligand synthons on the iron(II) ion as a matrix. The obtained polytopic cage complexes were characterized using elemental analysis, 1H NMR, MALDI-TOF MS and UV-vis spectra, and the single-crystal X-ray diffraction experiments. One of the obtained vinyl-terminated iron(II) phthalocyaninatoclathrochelates and its semiclathrochelate precursor were tested as monomers in a copolymerization reaction with styrene as the main component. These vinyl-terminated (semi)clathrochelate iron(II) complexes were found to be successfully copolymerized with this industrially important monomer, affording the intensely colored copolymer products. Because of a low solubility of the tested zirconium(IV) phthalocyaninate-capped tris-nioximate monomer in styrene as a solvent, a molar ratio of 1 : 500 was used. The obtained copolymer products and the kinetics of their formation were studied using GPC, FTIR, UV-vis, TGA and DSC methods. Even at such a low concentration of the Fe,Zr-binuclear metallocomplex component, an increase in the rate of the UV-light degradation of the organo-inorganic products, as well as in their thermal stability, was observed.

Dramatic Effect of A Ring Size of Alicyclic α-Dioximate Ligand Synthons on Kinetics of the Template Synthesis and of the Acidic Decomposition of the Methylboron-Capped Iron(II) Clathrochelates.

Kinetics and thermodynamics of the template synthesis and of the acidic decomposition of the methylboron-capped iron(II) tris-1,2-dioximates-the clathrochelate derivatives of six (nioxime)- and eight (octoxime)-membered alicyclic ligand synthons-were compared. In the case of a macrobicyclic iron(II) tris-nioximate, the plausible pathway of its formation contains a rate-determining stage and includes a reversible formation of an almost trigonal-antiprismatic (TAP) protonated tris-complex, followed by its monodeprotonation and addition of CH3B(OH)2. Thus, the formed TAP intermediate undergoes a multistep rate-determining stage of double cyclization with the elimination of two water molecules accompanied by a structural rearrangement, thus giving an almost trigonal-prismatic (TP) iron(II) semiclathrochelate. It easily undergoes a cross-linking with CH3B(OH)2, resulting in the elimination of H+ ion and in the formation of a macrobicyclic structure. In contrast, the analogous scheme for its macrobicyclic tris-octoximate analog was found to contain up to three initial stages affecting the overall synthesis reaction rate. The rates of acidic decomposition of the above clathrochelates were found to be also affected by the nature of their ribbed substituents. Therefore, the single crystal XRD experiments were performed in order to explain these results. The difference in the kinetic schemes of a formation of the boron-capped iron(II) tris-nioximates and tris-octoximates is explained by necessity of the substantial changes in a geometry of the latter ligand synthon, caused by its coordination to the iron(II) ion, due to both the higher distortion of the FeN6-coordination polyhedra, and the intramolecular sterical clashes in the molecules of the macrobicyclic iron(II) tris-octoximates.

Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents-The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s).

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their "click" 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, 1H, 1H{11B}, 11B, 11B{1H}, 19F{1H} and 13C{1H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN6-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28°. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C-H…H-B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C-H…F-B interaction with an adjacent carboranoclathrochelate molecule. The N-H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1H-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.

Spectroelectrochemical Properties and Catalytic Activity in Cyclohexane Oxidation of the Hybrid Zr/Hf-Phthalocyaninate-Capped Nickel(II) and Iron(II) tris-Pyridineoximates and Their Precursors.

The in situ spectroelectrochemical cyclic voltammetric studies of the antimony-monocapped nickel(II) and iron(II) tris-pyridineoximates with a labile triethylantimony cross-linking group and Zr(IV)/Hf(IV) phthalocyaninate complexes were performed in order to understand the nature of the redox events in the molecules of heterodinuclear zirconium(IV) and hafnium(IV) phthalocyaninate-capped derivatives. Electronic structures of their 1e-oxidized and 1e-electron-reduced forms were experimentally studied by electron paramagnetic resonance (EPR) spectroscopy and UV-vis-near-IR spectroelectrochemical experiments and supported by density functional theory (DFT) calculations. The investigated hybrid molecular systems that combine a transition metal (pseudo)clathrochelate and a Zr/Hf-phthalocyaninate moiety exhibit quite rich redox activity both in the cathodic and in the anodic region. These binuclear compounds and their precursors were tested as potential catalysts in oxidation reactions of cyclohexane and the results are discussed.

Synthesis and spectral characterization of the first fluorescein-tagged iron(ii) clathrochelates, their supramolecular interactions with globular proteins, and cellular uptake.

A fluorescein-tagged iron(ii) cage complex was obtained in a moderate total yield using a two-step synthetic procedure starting from its propargylamine-containing clathrochelate precursor. An 11-fold decrease in fluorescence quantum yield is observed in passing from the given fluorescein-based dye to its clathrochelate derivative. An excitation energy transfer from the terminal fluorescent group of the macrobicyclic molecule to its quasiaromatic highly π-conjugated clathrochelate framework can explain this effect. The kinetics of the hydrolysis of the acetyl groups of acetylated fluorescein azide and its clathrochelate derivative in the presence of one equivalent of BSA evidenced no strong supramolecular host-guest interactions between BSA and the tested compounds. Study of a chemical stability of the deacetylated iron(ii) clathrochelate suggested the formation of a supramolecular 1 : 1 BSA-clathrochelate assembly. Moreover, an addition of BSA or HSA to its solution caused the appearance of strong clathrochelate-based ICD outputs. The fluorescence emission anisotropy studies also evidenced the supramolecular binding of the fluorescein-tagged iron(ii) clathrochelate to the BSA macromolecule, leading to a high increase in this type of anisotropy. Subcellular uptake of the fluorescein-tagged molecules was visualized using fluorescence microscopy and showed its distribution to be mainly in the cytosol without entering the nucleus or accumulating in any other organelle. An X-rayed crystal of the above propargylamide macrobicyclic precursor with a reactive terminal C[triple bond, length as m-dash]C bond contains the clathrochelate molecules of two types, A and B. The encapsulated iron(ii) ion in these molecules is situated in the center of its FeN6-coordination polyhedron, the geometry of which is intermediate between a trigonal prism (TP) and a trigonal antiprism (TAP). The Fe-N distances vary from 1.8754(6) to 1.9286(4) Å and the heights h of their distorted TP-TAP polyhedra are very similar (2.30 and 2.31 Å); their values of φ are equal to 25.3 and 26.6°. In this crystal, the molecules of types A and B participate in different types of hydrogen bonding, giving H-bonded clathrochelate tetramers through their carboxylic and amide groups, respectively; these tetramers are connected to H-bonded chains.

Sensing of Proteins by ICD Response of Iron(II) Clathrochelates Functionalized by Carboxyalkylsulfide Groups.

Recognition of elements of protein tertiary structure is crucial for biotechnological and biomedical tasks; this makes the development of optical sensors for certain protein surface elements important. Herein, we demonstrated the ability of iron(II) clathrochelates (1-3) functionalized with mono-, di- and hexa-carboxyalkylsulfide to induce selective circular dichroism (CD) response upon binding to globular proteins. Thus, inherently CD-silent clathrochelates revealed selective inducing of CD spectra when binding to human serum albumin (HSA) (1, 2), beta-lactoglobuline (2) and bovine serum albumin (BSA) (3). Hence, functionalization of iron(II) clathrochelates with the carboxyalkylsulfide group appears to be a promising tool for the design of CD-probes sensitive to certain surface elements of proteins tertiary structure. Additionally, interaction of 1-3 with proteins was also studied by isothermal titration calorimetry, protein fluorescence quenching, electrospray ionization mass spectrometry (ESI-MS) and computer simulations. Formation of both 1:1 and 1:2 assemblies of HSA with 1-3 was evidenced by ESI-MS. A protein fluorescence quenching study suggests that 3 binds with both BSA and HSA via the sites close to Trp residues. Molecular docking calculations indicate that for both BSA and HSA, binding of 3 to Site I and to an "additional site" is more favorable energetically than binding to Site II.

Solvent-Induced Encapsulation of Cobalt(II) Ion by a Boron-Capped tris-Pyrazoloximate.

Boron-cross-linked cobalt(II) pseudoclathrochelate was obtained by the template reaction of 2-acetylpyrazoloxime, phenylboronic acid, and a new DMF cobalt(II) solvato complex with a decachloro-closo-decaborate dianion. As confirmed by single-crystal X-ray diffraction, this complex crystallizes with two symmetry-independent cobalt(II) pseudoclathrochelate cations, one decachloro-closo-decaborate dianion, one benzene, one dichloromethane solvent molecule, and two molecules of DMF. The latter act as pseudocapping fragments to the monocapped tris-pyrazoloximate ligands by forming N-H···O hydrogen bonds with their pyrazole groups. The CoIIN6-coordination polyhedra adopt a nearly ideal TP geometry with distortion angles φ equal to 1.22(16) and 2.58(17)° for two symmetry-independent pseudoclathrochelate cations, both containing the encapsulated cobalt(II) ion in its high-spin state (Co-N 2.115(4)-2.198(3) Å). Magnetic properties of this complex were studied both by dc-magnetometry and by solution-state NMR spectroscopy to reveal a high magnetic anisotropy, thus suggesting a large magnetic susceptibility tensor anisotropy (25.8 × 10-32 m3 at 298 K) and a large negative zero-field splitting energy (-85 cm-1). The results of magnetometry studies in the ac magnetic field suggest a single molecule magnet behavior of this TP complex with an effective magnetization reversal barrier of approximately 130 cm-1. Its pseudocapping DMF molecules that form H-bonds with tris-pyrazoloximate fragments are easy to substitute by strong H-bond acceptors, such as chloride ions and di- and tetramethylureas, thus affecting the magnetic properties of a whole pseudomacrobicyclic paramagnetic system.

A Trigonal Prismatic Cobalt(II) Complex as a Single Molecule Magnet with a Reduced Contribution from Quantum Tunneling.

Herein, we report a new trigonal prismatic cobalt(II) complex that behaves as a single molecule magnet. The obtained zero-field splitting, which is also directly accessed by THz-EPR spectroscopy (-102.5 cm-1 ), results in a large magnetization reversal barrier U of 205 cm-1 . Its effective value, however, is much lower (101 cm-1 ), even though there is practically no contribution from quantum tunneling to magnetization relaxation.

Dicarboxyl-terminated iron(ii) clathrochelates as ICD-reporters for globular proteins.

Cage metal complexes iron(ii) clathrochelates, which are inherently CD silent, were discovered to demonstrate intensive output in induced circular dichroism (ICD) spectra upon their assembly to albumins. With the aim to design clathrochelates as protein-sensitive CD reporters, the approach for the functionalization of one chelate α-dioximate fragment of the clathrochelate framework with two non-equivalent substituents was developed, and constitutional isomers of clathrochelate with two non-equivalent carboxyphenylsulfide groups were synthesized. The interaction of designed iron(ii) clathrochelates and their symmetric homologues with globular proteins (serum albumins, lysozyme, ß-lactoglobulin (BLG), trypsin, insulin) was studied by protein fluorescence quenching and CD techniques. A highly-intensive ICD output of the clathrochelates was observed upon their association with albumins and BLG. It was shown that in the presence of BLG, different clathrochelate isomers gave spectra of inverted signs, indicating the stabilization of opposite configurations (Λ or Δ) of the clathrochelate framework in the assembly with this protein. So, we suggest that the isomerism of the terminal carboxy group determined preferable configurations of the clathrochelate framework for the fixation in the protein binding site. MALDI TOF results show the formation of BLG-clathrochelate complex with ratio 1 : 1. Based on the docking simulations, the binding of the clathrochelate molecule (all isomers) to the main BLG binding site (calyx) in its open conformation is suggested. The above results point that the variation of the ribbed substituents at the clathrochelate framework is an effective tool to achieve the specificity of clathrochelate ICD reporting properties to the target protein.

Induced CD of iron(ii) clathrochelates: sensing of the structural and conformational alterations of serum albumins.

An ability of inherently achiral macrobicyclic metal complexes iron(ii) clathrochelates to acquire an induced CD (ICD) output in the visible spectral range upon interaction with bovine serum albumin (BSA) was recently discovered. In the present work, the CD-reporting properties of iron(ii) clathrochelates to proteins and the thermodynamic parameters of their binding to albumins are evaluated. It is shown that iron(ii) clathrochelates functionalized by six ribbed carboxyphenylsulfide groups are able to discriminate between serum albumins of relative structure (here human and bovine albumins) by giving distinct ICD spectra. Besides, by the variation of the shape and intensity of CD bands, these cage metal complexes reflect the pH-triggered alterations of the tertiary structure of albumins. The constitutional isomerism (ortho-, meta- or para-isomers) of terminal carboxyphenylsulfide groups of iron(ii) clathrochelates strongly affects both the character of their ICD output upon binding with proteins and the parameters of the formed guest-host associates. Using isothermal titration calorimetry, it was determined that cage metal complexes bearing meta- and ortho-isomers of carboxyphenylsulfide groups possess higher association constants (Ka ∼ 2 × 104 M-1) and clathrochelate-to-BSA binding ratios (n = 2) than the para-isomer (Ka ∼ 5 × 103 M-1, n = 1). The iron(ii) clathrochelates are suggested to be potential molecular three-dimensional scaffolds for the design of CD-sensitive reporters able to recognize specific elements of protein surfaces.

Determination of Large Zero-Field Splitting in High-Spin Co(I) Clathrochelates.

Zero-field splitting (ZFS) of three high-spin Co(I) ( S = 1) clathrochelate complexes was determined by frequency-domain Fourier-transform THz-EPR (FD-FT THz-EPR). The following axial and rhombic ZFS values ( D and E, respectively) were determined: [N( n-Bu)4]CoI(GmCl2)3(BPh)2 (1, D/ hc = +16.43(1) cm-1, E/ hc = 0.0(1) cm-1), [P(Me2N)4]CoI(GmCl2)3(BPh)2 (2, D/ hc = +16.67(4) cm-1, E/ hc = 0.0(1) cm-1), and [P(C6H5)4]CoI(GmCl2)3(BPh)2 (3, D/ hc = +16.72(2) cm-1, E/ hc = 0.24(3) cm-1). Complementary susceptibility χ T measurements and quantum chemistry calculations on 1 revealed hard-axis-type magnetic anisotropy and allowed for a correlation of ZFS and the electronic structure. Increased rhombicity of 3 as compared to 1 and 2 was assigned to symmetry changes of the ligand structure induced by the change of the counterion. 1 and 3 exhibited temperature-dependent ZFS values. Possible reasons for this phenomenon, such as structural changes and weak chain-like intermolecular antiferromagnetic interactions, are discussed.

Synthesis and characterization of an Fe(i) cage complex with high stability towards strong H-acids.

The first synthesized and X-ray structurally characterized "classical" iron(i) dioximate showed an unrivaled stability towards strong acids, thus calling for a reassessment of the origins of the electrocatalytic activity of similar low-valent cobalt and iron cage complexes with electron-withdrawing ribbed substituents, shown previously to be effective electrocatalysts of the HER.