Search Results (14)

Derivatives of natural amino acids are selectively absorbed by many types of tumour cells. This makes the use of amino acids, especially polyfunctional ones, attractive as a basis in the design of low-toxicity agents for targeted boron delivery for boron neutron capture therapy (BNCT) of tumours. We synthesized a series of new (S)-ornithine and (S)-lysine derivatives containing a 7,8-dicarba-nido-undecaborane (nido-carborane) residue attached to the amino group in the side chain or alpha position. The MTT assay demonstrated moderate cytotoxicity of the lysine and ornithine derivatives containing a nido-carborane residue in the side chain. It has been found that sodium salt of N^ε-(nido-carboran-7-yl)acetyl-(S)-lysine is capable of accumulation by MDA-MB-231 (human breast carcinoma) and SK-Mel 28 (human melanoma) cell lines, providing a boron concentration of up to 0.67 µg/10⁶ cells in in vitro experiments. This (S)-lysine derivative containing a nido-carborane residue in the side chain can be considered as a promising compound for in-depth study in vivo experiments aimed at designing an efficient boron delivery agent for BNCT. Full article

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C₂B₉H₁₁)₂], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of ¹⁰B-enriched trimethylammonium salt of nido-[7,8-C₂¹⁰B₉H₁₂]⁻o-carborane, along with the cesium and sodium salts of [o-¹⁰COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[¹⁰B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-¹⁰COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-¹⁰COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-¹⁰COSAN] would be potentially useful to treat head and neck cancer with BNCT. Full article

Introduction of Cl and O atoms into C₄-vinyl carbocations was studied by X-ray diffraction analysis and IR spectroscopy. Chlorine atoms are weak electron acceptors in ordinary molecules but, within vinyl carbocations, manifest themselves as strong electron donors that accept a positive charge. The attachment of a Cl atom directly to a C=C bond leads to an increase in the e-density on it, exceeding that of the common double bond. The positive charge should be concentrated on the Cl atom, and weak δ⁻ may appear on the C=C bond. More distant attachment of the Cl atom, e.g., to a C atom adjacent to the C=C bond, has a weaker effect on it. If two Cl atoms are attached to the C_γ atom of the vinyl cation, as in Cl₂C_γC_δHC_αHCH₃, then the cation switches to the allyl type with two practically equivalent and almost uncharged C_γC_δC_α bonds. When such a strong nucleophile as the O atom is introduced into the carbocation, a protonated ester molecule with a C–O(H⁺)–C group and a C=C bond forms. Nonetheless, in the future, there is still a possibility of obtaining carbocations with a non-protonated C–O–C group. Full article

In this contribution, the first amidinate and amidine derivatives of p-carborane are described. Double lithiation of p-carborane (1) with n-butyllithium followed by treatment with 1,3-diorganocarbodiimides, R–N=C=N–R (R = ⁱPr, Cy (= cyclohexyl)), in DME or THF afforded the new p-carboranylamidinate salts p-C₂H₁₀B₁₀[C(NⁱPr)₂Li(DME)]₂ (2) and p-C₂H₁₀B₁₀[C(NCy)₂Li(THF)₂]₂ (3). Subsequent treatment of 2 and 3 with 2 equiv. of chlorotrimethylsilane (Me₃SiCl) provided the silylated neutral bis(amidine) derivatives p-C₂H₁₀B₁₀[C{ⁱPrN(SiMe₃)}(=NⁱPr)]₂ (4) and p-C₂H₁₀B₁₀[C{CyN(SiMe₃)}(=NCy)]₂ (5). The new compounds 3 and 4 have been structurally characterized by single-crystal X-ray diffraction. The lithium carboranylamidinate 3 comprises a rare trigonal planar coordination geometry around the lithium ions. Full article

New carboranyl thioethers 1-MeO(CH₂)_nS-1,2-C₂B₁₀H₁₁ (n = 2, 3) were prepared by the alkylation of the trimethylammonium salt of 1-mercapto-ortho-carborane with 1-bromo- 2-methoxyethane and 1-bromo-3-methoxypropane, respectively. Their deboronation with cesium fluoride in ethanol gave the corresponding nido-carboranes Cs[7-MeO(CH₂)_nS-7,8-C₂B₉H₁₁] (n = 2, 3). The reactions of Cs[7-MeO(CH₂)₂S-7,8-C₂B₉H₁₁] with various nickel(II) phosphine complexes [(dppe)NiCl₂] and [(R’R₂P)₂NiCl₂] (R = R’ = Ph, Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) were studied and a series of nickelacarboranes 3,3-dppe-1-MeO(CH₂)₂S-closo-3,1,2-NiC₂B₉H₁₀ and 3,3- (R’R₂P)₂-1-MeO(CH₂)₂S-closo-3,1,2-NiC₂B₉H₁₀ (R = R’ = Bu; R = Me, R’ = Ph; R = Ph, R’ = Me, Et) was prepared. The molecular crystal structure of 3,3-dppe-1-MeO(CH₂)₂S-closo-3,1,2-NiC₂B₉H₁₀ was determined by single-crystal X-ray diffraction. Full article

X-ray diffraction analysis and IR spectroscopy were used to study the products of the interaction of vinyl cations C₃H₅⁺ and C₄H₇⁺ (Cat⁺) (as salts of carborane anion CHB₁₁Cl₁₁⁻) with basic molecules of water, alcohols, and acetone that can crystallize from solutions in dichloromethane and C₆HF₅. Interaction with water, as content increased, proceeded via three-stages. (1) adduct Cat⁺·OH₂ forms in which H₂O binds (through the O atom) to the C=C⁺ bond of the cation with the same strength as seen in the binding to Na in Na(H₂O)₆⁺. (2) H⁺ is transferred from cation Cat⁺·OH₂ to a water molecule forming H₃O⁺ and alcohol molecules (L) having the CH=CHOH entity. The O- atom of alcohols is attached to the H atom of the C=C⁺-H moiety of Cat⁺ thereby forming a very strong asymmetric H–bond, (C=)C⁺-H⋅⋅⋅O. (3) Finally all vinyl cations are converted into alcohol molecule L and H₃O⁺ cations, yielding proton disolvates L-H⁺-L with a symmetric very strong H-bond. When an acetone molecule (Ac) interacts with Cat⁺, H⁺ is transferred to Ac giving rise to a reactive carbene and proton disolvate Ac-H⁺-Ac. Thus, the alleged high reactivity of vinyl cations seems to be an exaggeration. Full article

This review systematizes data on the coordination ability of mono- and disubstituted derivatives of boron cluster anions and carboranes in complexation with transition metals. Boron clusters anions [B_nH_n]^2–, monocarborane anions [CB_nH_n–1]^–, and dicarboranes [C₂B_nH_n–2] (with non-functionalized carbon atoms) (n = 10, 12) containing the B–X exo-polyhedral bonds (X = N, O, S, Hal) are discussed. Synthesis and structural features of complexes known to date are described. The effect of complexing metal and substituent attached to the boron cage on the composition and structures of the final complexes is analyzed. It has been established that substituted derivatives of boron cluster anions and carboranes can act as both ligands and counterions. A complexing agent can coordinate substituted derivatives of the boron cluster anions due to three-center two-electron 3c2e MHB bonds, by the substituent functional groups, or a mixed type of coordination can be realized, through the BH groups of the boron cage and the substituent. As for B-substituted carboranes, complexes with coordinated substituents or salts with non-coordinated carborane derivatives have been isolated; compounds with MHB bonding are not characteristic of carboranes. Full article

The basic macrocyclic octapyridinotetrapyrazinoporphyrazine In^III complex of formula [Py₈TPyzPzIn(OAc)]·8H₂O, prepared by reaction of the free ligand [Py₈TPyzPzH₂]·2H₂O with In(OAc)₃, is a stable-to-air species of which the structure has been studied by its X-ray powder diffraction and mass spectra and characterization operated by IR and UV-visible spectral behavior. The complex has been further examined and proven to be of potential interest for its response as an anticancer agent in the field of photodynamic therapy (PDT), the value of Φ_Δ = 0.55 (in DMF) being in the range of 0.4–0.6 at the level of similar phthalocyanine and porphyrazine analogs and qualifying the species as a highly efficient anticancer agent. Planned parallel types of investigation, including their photoactive behaviour in PDT, have been extended to the mononuclear octacation [(2-Mepy)₈TPyzPzIn(OAc)]⁸⁺ (salted by iodide ions) and the heteropentanuclear derivatives [(M’Cl₂)₄Py₈TPyzPzIn(OAc)]·xH₂O (M’ = Pd^II, x = 8; Pt^II, x = 1)) and [{(Pd(CBT)₂)₄}Py₈TPyzPzIn(OAc)]·19H₂O (CBT = m-carborane-1-thiolate anion). Full article

The sulfa-Michael addition reaction was applied for the two-step synthesis of o-carboranyl cysteine 1-HOOCCH(NH₂)CH₂S-1,2-C₂B₁₀H₁₁ from the trimethylammonium salt of 1-mercapto-o-carborane and methyl 2-acetamidoacrylate. To avoid the decapitation of o-carborane into its nido-form, the “free of base” method under mild conditions in a system of two immiscible solvents toluene-H₂O was developed. The replacement of H₂O by ²H₂O resulted in carboranyl-cysteine containing a deuterium label at the α-position of the amino acid 1-HOOCCD(NH₂)CH₂S-1,2-C₂B₁₀H₁₁. The structure of the protected o-carboranyl cysteine was determined by single-crystal X-ray diffraction. The obtained compounds can be considered as potential agents for the Boron Neutron Capture Therapy of cancer. Full article

In order to explore the angular strain role on the ability of Be to form strong beryllium bonds, a theoretical study of the complexes of four beryllium derivatives of orthocloso-carboranes with eight molecules (CO, N₂, NCH, CNH, OH₂, SH₂, NH₃, and PH₃) acting as Lewis bases has been carried out at the G4 computational level. The results for these complexes, which contain besides Be other electron-deficient elements, such as B, have been compared with the analogous ones formed by three beryllium salts (BeCl₂, CO₃Be and SO₄Be) with the same set of Lewis bases. The results show the presence of large and positive values of the electrostatic potential associated to the beryllium atoms in the isolated four beryllium derivatives of ortho-carboranes, evidencing an intrinsically strong acidic nature. In addition, the LUMO orbital in these systems is also associated to the beryllium atom. These features led to short intermolecular distances and large dissociation energies in the complexes of the beryllium derivatives of ortho-carboranes with the Lewis bases. Notably, as a consequence of the special framework provided by the ortho-carboranes, some of these dissociation energies are larger than the corresponding beryllium bonds in the already strongly bound SO₄Be complexes, in particular for N₂ and CO bases. The localized molecular orbital energy decomposition analysis (LMOEDA) shows that among the attractive terms associated with the dissociation energy, the electrostatic term is the most important one, except for the complexes with the two previously mentioned weakest bases (N₂ and CO), where the polarization term dominates. Hence, these results contribute to further confirm the importance of bending on the beryllium environment leading to strong interactions through the formation of beryllium bonds. Full article

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by ¹H, ¹³C, and ¹¹B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively. Full article

Dihydrogen bonds attract much attention as unconventional hydrogen bonds between strong donors of H-bonding and polyhedral (car)borane cages with delocalized charge density. Salts of closo-borate anions [B₁₀H₁₀]²⁻ and [B₁₂H₁₂]²⁻ with protonated organic ligands 2,2’-dipyridylamine (BPA), 1,10-phenanthroline (Phen), and rhodamine 6G (Rh6G) were selectively synthesized to investigate N−H...H−B intermolecular bonding. It was found that the salts contain monoprotonated and/or diprotonated N-containing cations at different ratios. Protonation of the ligands can be implemented in an acidic medium or in water because of hydrolysis of metal cations resulting in the release of H₃O⁺ cations into the reaction solution. Six novel compounds were characterized by X-ray diffraction and FT-IR spectroscopy. It was found that strong dihydrogen bonds manifest themselves in FT-IR spectra that allows one to use this technique even in the absence of crystallographic data. Full article

9-Dimethyloxonium, 10-dimethyloxonium, 9-methoxy and 10-methoxy derivatives of nido-carborane (9-Me₂O-7,8-C₂B₉H₁₁, 10-Me₂O-7,8-C₂B₉H₁₁, [9-MeO-7,8-C₂B₉H₁₁]⁻, and [10-MeO-7,8-C₂B₉H₁₁]⁻, respectively) were prepared by the reaction of the parent nido-carborane [7,8-C₂B₉H₁₂]⁻ with mercury(II) chloride in a mixture of benzene and dimethoxymethane. Reactions of the 9 and 10-dimethyloxonium derivatives with triethylamine, pyridine, and 3-methyl-6-nitro-1H-indazole result in their N-methylation with the formation of the corresponding salts with 9 and 10-methoxy-nido-carborane anions. The reaction of the symmetrical methoxy derivative [10-MeO-7,8-C₂B₉H₁₁]⁻ with anhydrous FeCl₂ in tetrahydrofuran in the presence of t-BuOK results in the corresponding paramagnetic iron bis(dicarbollide) complex [8,8′-(MeO)₂-3,3′-Fe(1,2-C₂B₉H₁₀)₂]⁻, whereas the similar reactions of the asymmetrical methoxy derivative [9-MeO-7,8-C₂B₉H₁₁]⁻ with FeCl₂ and CoCl₂ presumably produce the 4,7′-isomers [4,7′-(MeO)₂-3,3′-M(1,2-C₂B₉H₁₀)₂]⁻ (M = Fe, Co) rather than a mixture of rac-4,7′- and meso-4,4′-isomers. Full article