BODIPY Conjugates as Functional Compounds for Medical Diagnostics and Treatment

Fluorescent dyes absorbing and emitting in the visible and near-IR regions are promising for the development of fluorescent probes for labeling and bio-visualization of body cells. The ability to absorb and emit in the long-wavelength region increases the efficiency of recording the spectral signals of the probes due to the higher permeability of the skin layers. Compared to other fluorescent dyes, BODIPYs are attractive due to their excellent photophysical properties–narrow absorption and emission, intense fluorescence, simple signal modulation for the practical applications. As part of conjugates with biomolecules, BODIPY could act as a biomarker, but as therapeutic agent, which allows solving several problems at once-labeling or bioimaging and treatment based on the suppression of pathogenic microflora and cancer cells, which provides a huge potential for practical application of BODIPY conjugates in medicine. The review is devoted to the discussion of the recent, promising directions of BODIPY application in the field of conjugation with biomolecules. The first direction is associated with the development of BODIPY conjugates with drugs, including compounds of platinum, paclitaxel, chlorambucil, isoxazole, capsaicin, etc. The second direction is devoted to the labeling of vitamins, hormones, lipids, and other biomolecules to control the processes of their transport, localization in target cells, and metabolism. Within the framework of the third direction, the problem of obtaining functional optically active materials by conjugating BODIPY with other colored and fluorescent particles, in particular, phthalocyanines, is being solved.     

Magnetic resonance and structural investigations of (monooxooctaethylchlorinato)iron(III) chloride and its bis(imidazole) complex

(Monooxooctaethylchlorinato)iron(III) chloride, (oxo-OEC)FeCl, 1, has been investigated by X-ray crystallography and by 1H NMR spectroscopy. Its bis(imidazole-d4) complex has been studied by multidimensional 1H NMR and EPR spectroscopies, and the results are compared to those for the bis(Im-d4) complex of (octaethylchlorinato)iron(III) chloride, (OEC)FeCl, 2. EPR and NMR results show that both [(oxo-OEC)Fe(Im-d4)2]Cl and [(OEC)Fe(Im-d4)2]Cl are low-spin Fe(III) complexes with (d(xy))2 (d(xz),d(yz))3 electronic ground states, both at 4.2 K (EPR spectra) and at ambient temperatures utilized for solution NMR studies. The pattern of chemical shifts of the pyrrole-CH2 and meso protons are similar, with the 8,17-carbons having the largest and the 12,13-carbons having the smallest spin densities in each case, except that [(OEC)Fe(Im-d4)2]Cl has a slightly wider range of pyrrole-CH2 chemical shifts and more resonances are observed for [(oxo-OEC)Fe(Im-d4)2]Cl due to its lower symmetry. Full proton resonance assignments for both complexes have been made from COSY, NOESY, and NOE difference experiments.     

Synthesis and characterization of germanium, tin, phosphorus, iron, and rhodium complexes of tris(pentafluorophenyl)corrole, and the utilization of the iron and rhodium corroles as cyclopropanation catalysts

The germanium(IV), tin(IV). and phosphorus(v) complexes of tris(pentafluorophenyl)corrole were prepared and investigated by electrochemistry for elucidation of the electrochemical HOMO-LUMO gap of the corrole and the spectroscopic characteristics of the corrole pi radical cation. This information was found to be highly valuable for assigning the oxidation states in the various iron corroles that were prepared. Two iron corroles and the rhodium(I) complex of an N-substituted corrole were fully characterized by X-ray crystallography and all the transition metal corroles were examined as cyclopropanation catalysts. All iron (except the NO-ligated) and rhodium corroles are excellent catalysts for cyclopropanation of styrene, with the latter displaying superior selectivities. An investigation of the effect of the oxidation state of the metal and its ligands leads to the conclusion that for iron corroles the catalytically active form is iron(III), while all accesible oxidation states of rhodium are active.     

NMR and EPR spectroscopic and structural studies of low-spin, (d(xz),d(y)(z))(4)(d(x)(y))(1) ground state Fe(III) bis-tert-butylisocyanide complexes of dodecasubstituted porphyrins

The bis-(1,1-dimethylethylisocyanide) (tert-butylisocyanide) complexes of three iron porphyrinates (2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin, OETPP; 2,3,7,8,12,13,17,18-octamethyl-5,10,15,20-tetraphenylporphyrin, OMTPP; and 2,3,7,8,12,13,17,18-tetra-beta,beta'-tetramethylene-5,10,15,20-tetraphenylporphyrin, TC(6)TPP) have been prepared and studied by EPR and (1)H NMR spectroscopy. From EPR and NMR spectroscopic results it has been found that the ground states of the bis-(t-BuNC) complexes of OETPP, OMTPP, and TC(6)TPP are represented mainly (99.1-99.4%) as (d(xz,)d(yz))(4)(d(xy))(1) electron configurations, with an excited state lying 700 cm(-)(1) to higher energy for the OMTPP complex, and probably at lower and higher energies, respectively, for the OETPP and TC(6)TPP complexes. In the (1)H NMR spectra the (d(xz,)d(yz))(4)(d(xy))(1) electron configurations of all three complexes are indicated by the large and positive meso-phenyl-H shift differences, delta(m)-delta(o) and delta(m)-delta(p), and close to the diamagnetic shifts of groups (CH(3) or CH(2)) directly attached to the beta-carbons. However, in comparison to meso-only substituted porphyrinates such as [FeTPP(t-BuNC)(2)]ClO(4), the meso-phenyl shift differences are much smaller, especially for the OETPP complex. 2D NOESY spectra show that the flexibility of the porphyrin core decreases with increasing nonplanar distortion in the order TC(6)TPP > OMTPP > OETPP and in the same order the stability of the binding to t-BuNC ligands decreases. In addition, the structures of two crystalline forms of [FeOMTPP(t-BuNC)(2)]ClO(4) have been determined by X-ray crystallography. Both structures showed purely saddled porphyrin cores and somewhat off-axis binding of the isocyanide ligands. To our knowledge, this is the first example of a porphyrin complex with a purely saddled conformation that adopts the (d(xz,)d(yz))(4)(d(xy))(1) ground state. All structurally-characterized complexes of this electron configuration reported previously are ruffled. Therefore, we conclude that a ruffled geometry stabilizes the (d(xz,)d(yz))(4)(d(xy))(1) ground state, but is not necessary for its existence.     

Magnetic resonance spectroscopic investigations of the electronic ground and excited states in strongly nonplanar iron(III) dodecasubstituted porphyrins

A series of axially ligated complexes of iron(III) octamethyltetraphenylporphyrin, (OMTPP)Fe(III), octaethyltetraphenylporphyrin, (OETPP)Fe(III), its perfluorinated phenyl analogue, (F(20)OETPP)Fe(III), and tetra-(beta,beta'-tetramethylene)tetraphenylporphyrin, (TC(6)TPP)Fe(III), have been prepared and characterized by (1)H NMR spectroscopy: chloride, perchlorate, bis-4-(dimethylamino)pyridine, bis-1-methylimidazole, and bis-cyanide. Complete spectral assignments have been made using 1D and 2D techniques. The temperature dependences of the proton resonances of the complexes show significant deviations from simple Curie behavior and evidence of ligand exchange, ligand rotation, and porphyrin ring inversion at ambient temperatures. At temperatures below the point where dynamics effects contribute, the temperature dependences of the proton chemical shifts of the complexes could be fit to an expanded version of the Curie law using a temperature-dependent fitting program developed in our laboratory that includes consideration of a thermally accessible excited state. The results show that, although the ground state differs for various axial ligand complexes and is usually fully consistent with that observed by EPR spectroscopy at 4.2 K, the excited state often has S = (3)/(2) (or S = (5)/(2) in the cases where the ground state has S = (3)/(2)). The EPR spectra (4.2 K) of bis-4-(dimethylamino)pyridine and bis-1-methylimidazole complexes show "large-g(max)" signals with g(max) = 3.20 and 3.12, respectively, and the latter also shows a normal rhombic EPR signal, indicating the presence of low-spin (LS) (d(xy))(2)(d(xz),d(yz))(3) ground states for both. The bis-cyanide complex also yields a large-g(max) EPR spectrum with g = 3.49 and other features that could suggest that some molecules have the (d(xz),d(yz))(4)(d(xy))(1) ground state. The EPR spectra of all five-coordinate chloride complexes have characteristic features of predominantly S = (5)/(2) ground-state systems with admixture of 1-10% of S = (3)/(2) character.     

Slow backbone dynamics of chicken villin headpiece subdomain probed by NMR C′?N cross‐correlated relaxation

We have investigated slow correlated motions of neighboring carbonyl and nitrogen nuclei in the backbone of chicken villin headpiece subdomain. Cross‐correlated chemical shift modulation experiments were performed at three temperatures where the protein remains in its folded state. The results at 8 °C demonstrate the presence of microseconds to milliseconds timescale motions for a number of residues belonging both to helices and unstructured regions. As the temperature is raised, the motions become progressively less visible. The reduction of the contributions of slow motions into the cross‐correlated relaxation rate with the rise in temperature is caused by the increase of the chemical exchange rate constants for the slow motion processes. Copyright © 2009 John Wiley & Sons, Ltd.     

Reversible intramolecular Dieckmann-type condensation of 2-(2-hydroxymethyl-5,5,6-trimethoxytetrahydropyran-3-ylcarbonyl)-cyclopentanone: an alternative access to medium-sized lactones

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