ABSTRACT
The indolocarbazoles are an important class of nitrogen heterocycles which has evolved significantly in recent years, with numerous studies focusing on their diverse biological effects, or targeting new materials with potential applications in organic electronics. This review aims at providing a broad survey of the chemistry and properties of indolocarbazoles from an interdisciplinary point of view, with particular emphasis on practical synthetic aspects, as well as certain topics which have not been previously accounted for in detail, such as the occurrence, formation, biological activities, and metabolism of indolo[3,2- b]carbazoles. The literature of the past decade forms the basis of the text, which is further supplemented with older key references.
ABSTRACT
Activation of the aryl hydrocarbon receptor (AhR), a conserved transcription factor best known as a target for highly toxic halogenated substances such as dioxin, under normal xenobiotic-free conditions is of considerable scientific interest. We have demonstrated previously that a photoproduct of tryptophan, 6-formylindolo[3,2-b]carbazole (FICZ), fulfills the criteria for an endogenous ligand for this receptor and proposed that this compound is the enigmatic mediator of the physiological functions of AhR. Here, we describe novel light-independent pathways by which FICZ can be formed. The oxidant H2O2 was shown to convert tryptophan to FICZ on its own in the absence of light. The enzymatic deamination of tryptamine yielded indole-3-acetaldehyde (I3A), which then rearranged to FICZ and its oxidation product, indolo[3,2-b]carbazole-6-carboxylic acid (CICZ). Indole-3-pyruvate (I3P) also produced I3A, FICZ, and CICZ. Malassezia yeast species, which constitute a part of the normal skin microbiota, produce a number of AhR activators from tryptophan. We identified both FICZ and CICZ among those products. Formation of FICZ from tryptophan or I3P produces a complex mixture of indole derivatives, some of which are CYP1A1 inhibitors. These can hinder the cellular clearance of FICZ and thereby increase its power as an AhR agonist. We present a general molecular mechanism involving dehydrogenations and oxidative coupling for the formation of FICZ in which I3A is the important precursor. In conclusion, our results suggest that FICZ is likely to be formed systemically.
Subject(s)
Carbazoles/pharmacology , Cytochrome P-450 CYP1A1/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Receptors, Aryl Hydrocarbon/agonists , Carbazoles/chemical synthesis , Carbazoles/chemistry , Cytochrome P-450 CYP1A1/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Light , Molecular Structure , Structure-Activity RelationshipABSTRACT
Reaction of P4S10 in hot pyridine produces a crystalline solid which can be collected and used for thionations in other solvents such as acetonitrile and sulfolane. The biologically active natural products tryptanthrine, rutaecarpine, 7,8-dehydrorutaecarpine, and some related compounds have now been converted to thionated versions simply by heating the molecules with this thionating reagent in sulfolane (typically at 135 °C for 20 min) followed by a workup in water. No chromatography was necessary.
ABSTRACT
Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.
Subject(s)
Indoles/chemistry , Indoles/chemical synthesis , Isatin/chemistry , Quinazolines/chemical synthesis , Quinazolinones/chemical synthesis , Spiro Compounds/chemistry , Spiro Compounds/chemical synthesis , ortho-Aminobenzoates/chemistry , Crystallography, X-Ray , Molecular Structure , Oxidation-Reduction , Oxindoles , Quinazolines/chemistry , Quinazolinones/chemistryABSTRACT
A model for physician-led team triage was evaluated at the Emergency Department at the University hospital of Örebro, Sweden. Data from 1600 patients indicate that this work model reduces length of stay, time to physician assessment, emergency department occupancy, rate of admission and the proportion of patients in need of close monitoring. The project was conducted without any change in the number of physicians, nurses or staff nurses working in the Emergency Department.
Subject(s)
Emergency Service, Hospital/organization & administration , Patient Care Team/organization & administration , Triage/methods , Adult , Aged , Aged, 80 and over , Bed Occupancy/statistics & numerical data , Cohort Studies , Critical Pathways , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Nurses , Nursing Assistants , Physicians , Sweden , Time FactorsABSTRACT
Vitamins with antioxidant properties have the ability to act as pro-oxidants, inducing oxidative damage and oxidative stress as opposed to preventing it. While vitamin supplements are commonly consumed, the scientific evidence for their health beneficial effects is inconclusive. In fact, even harmful effects have been reported. The present study aimed to investigate and compare pro-oxidant properties of different antioxidants and vitamins commonly found in dietary supplements, at concentrations of physiological relevance, alone or in combination with metals also found in supplements. Focus was on damages related to DNA. The vitamins' chemical oxidation potencies were studied by measuring the amount of the oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formed from the DNA nucleoside deoxyguanosine (dG) after vitamin exposure, using a high-performance liquid chromatography system with electrochemical and ultraviolet detection. To study the vitamins' ability to cause DNA damage to cultured cells, promyelocytic leukemia cells (HL-60) were exposed to vitamins, and strand breaks, alkali-labile sites and oxidative DNA lesions, i.e. formamido pyrimidine DNA glycosylase-sensitive sites, were detected using the comet assay. Vitamins A and C chemically induced oxidation of dG, alone and in synergism with iron or copper, whereas only vitamin C and copper induced DNA damage in cultured cells. Contrary, vitamins B1, B2, B3, B6 and B12, ß-carotene, folic acid, α-tocopherol, δ-tocopherol or γ-tocopherol did not induce oxidative damage to dG, while lycopene induced a weak dose-response increase. Taken together, vitamin C and copper stood out with the strongest oxidative potency, which is of potential concern since both substances are commonly found in multivitamins.
Subject(s)
Antioxidants/pharmacology , DNA Damage/drug effects , DNA/chemistry , Deoxyguanosine/chemistry , Metals/pharmacology , Reactive Oxygen Species/pharmacology , Vitamins/pharmacology , 8-Hydroxy-2'-Deoxyguanosine , Chromatography, High Pressure Liquid , Comet Assay , DNA-Formamidopyrimidine Glycosylase/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/analysis , Deoxyguanosine/metabolism , Dietary Supplements , Drug Synergism , HL-60 Cells , Humans , Oxidation-Reduction , Oxidative StressABSTRACT
In accordance with the European Parliament and Council's directive, vitamin A and C supplements can include any of four (vitamin A) or five (vitamin C) specified compounds. This study focuses on these compounds and compares their abilities to affect the DNA and viability of cells in culture, but also their potencies to chemically oxidise the DNA nucleoside deoxyguanosine (dG). To study the vitamins' strict chemical oxidation potencies, dG was exposed to vitamin solution and the amount of the oxidation product 8'-hydroxydeoxyguanosine (8-oxodG) formed was estimated using a high-performance liquid chromatography system with electrochemical and ultraviolet detection. The vitamin's ability to cause DNA damage to promyelocytic leukaemia cells (HL-60), as detected by strand breaks, alkaline labile sites and formamido pyrimidine DNA glycosylase (FPG)-sensitive sites was, after vitamin exposure, measured using the comet assay and cytotoxicity was estimated using trypan blue staining. The results highlight that vitamin A and C compounds found in supplements do have different properties, chemically as well as in a cellular system. Among the vitamin C compounds, ascorbic acid, sodium ascorbate and calcium ascorbate stood out causing both oxidation to dG and cytotoxicity to cells. The vitamin A compounds retinol, retinyl acetate and retinal (a breakdown product found in vivo) caused oxidation of dG, while retinal was the only compound causing cytotoxicity, giving rise to an almost complete cell death. ß-carotene caused, as the only vitamin compound, a small increase in FPG-sensitive sites. It is concluded that even though the compounds are found under the same name (vitamin A or C), they do have different properties linked to oxidation, cytotoxicity and DNA damage.
Subject(s)
Ascorbic Acid/pharmacology , DNA/metabolism , Deoxyguanosine/metabolism , Dietary Supplements , Vitamin A/pharmacology , Ascorbic Acid/chemistry , Cell Death/drug effects , Cell Survival/drug effects , Comet Assay , DNA Damage , DNA-Formamidopyrimidine Glycosylase/metabolism , HL-60 Cells , Humans , Oxidation-Reduction/drug effects , Vitamin A/chemistryABSTRACT
Practical total syntheses of the natural products fuligocandin A (2a) and fuligocandin B (3) have been achieved through a convergent strategy depending on the Eschenmoser episulfide contraction as a key step. Conducting the reaction in DMSO proved to be an efficient and general method for the synthesis of a variety of vinylogous amides, such as azepan-2-ylidenepropan-2-one.
Subject(s)
Amides/chemistry , Amides/chemical synthesis , Dimethyl Sulfoxide/chemistry , Proline/analogs & derivatives , Sulfides/chemistry , Proline/chemical synthesisABSTRACT
Tetraphosphorus decasulfide (P(4)S(10)) in pyridine has been used as a thionating agent for a long period of time. The moisture-sensitive reagent has now been isolated in crystalline form, and the detailed structure has been determined by X-ray crystallography. The thionating power of this storable reagent has been studied and transferred to solvents such as acetonitrile in which it has proven to be synthetically useful and exceptionally selective. Its properties have been compared with the so-called Lawesson reagent (LR). Particularly interesting are the results from thionations at relatively high temperatures (â¼165 °C) in dimethyl sulfone as solvent. Under these conditions, for instance, acridone and 3-acetylindole could quickly be transformed to the corresponding thionated derivatives. Glycylglycine similarly gave piperazinedithione. At these temperatures, LR is inefficient due to rapid decomposition. The thionated products are generally cleaner and more easy to obtain because in the crystalline reagent, impurities which invariably are present in the conventional reagents, P(4)S(10) in pyridine or LR, have been removed.
Subject(s)
Acetonitriles/chemistry , Dimethyl Sulfoxide/chemistry , Phosphorus/chemistry , Pyridines/chemistry , Solvents/chemistry , Sulfones/chemistry , Sulfur/chemistry , Amides/chemistry , Models, Molecular , Molecular ConformationABSTRACT
The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of low-molecular-weight compounds in order to identify compounds that can restore wild-type function to mutant p53. We found one compound capable of inducing apoptosis in human tumor cells through restoration of the transcriptional transactivation function to mutant p53. This molecule, named PRIMA-1, restored sequence-specific DNA binding and the active conformation to mutant p53 proteins in vitro and in living cells. PRIMA-1 rescued both DNA contact and structural p53 mutants. In vivo studies in mice revealed an antitumor effect with no apparent toxicity. This molecule may serve as a lead compound for the development of anticancer drugs targeting mutant p53.
Subject(s)
Apoptosis/drug effects , Aza Compounds/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Organic Chemicals/pharmacology , Transcriptional Activation/drug effects , Tumor Suppressor Protein p53/physiology , Animals , Antineoplastic Agents/therapeutic use , Apoptosis/physiology , Aza Compounds/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Cell Separation , Flow Cytometry , Genes, Reporter , Humans , In Situ Nick-End Labeling , Mice , Molecular Structure , Molecular Weight , Mutation , Neoplasms/drug therapy , Organic Chemicals/therapeutic use , Protein Conformation , Transcriptional Activation/physiology , Transplantation, Heterologous , Tumor Cells, Cultured , Tumor Suppressor Protein p53/geneticsABSTRACT
The p53 tumor suppressor gene is inactivated by point mutation in a large fraction of human tumors, allowing evasion of apoptosis and tumor progression. p53 mutation is often associated with increased resistance to therapy. Pharmacological reactivation of mutant p53 is an attractive therapeutic strategy. We previously identified p53 reactivation and induction of massive apoptosis, a low-molecular weight compound that suppresses the growth of cancer cells in a mutant p53-dependent manner. Here, we report the identification and characterization of an extract from the terrestrial plant Brachylaena ramiflora (Asteraceae) that preferentially induces apoptosis in human tumor cells expressing mutant p53. Further analysis of this extract and identification of active compounds may provide novel structural scaffolds for the development of mutant p53-targeting anticancer drugs.
Subject(s)
Apoptosis/drug effects , Asteraceae/chemistry , Mutation , Plant Extracts/pharmacology , Tumor Suppressor Protein p53/genetics , Caspases/metabolism , Cell Line, Tumor , Enzyme Activation , Flow Cytometry , Humans , Reactive Oxygen Species/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Addition of organometallics to N-(alpha-haloacyl)-o-aminobenzonitrile resulted in the formation of 2,5-disubstituted 1,4-benzodiazepin-3-ones, whereas N-(beta-haloacyl)-o-aminobenzonitrile gave 2,6-disubstituted 1,5-benzodiazocin-4-ones under similar conditions. Initial cylization of N-(beta-haloacyl)-o-aminobenzonitrile to obtain the corresponding lactam (e.g.alpha,alpha-dimethyl-N-(2-cyanophenyl)-beta-lactam) increased the yield of 1,5-benzodiazocin-4-ones significantly. Somewhat surprisingly, addition of lithium reagents to N-(beta-haloacyl)-o-aminobenzonitrile gave 4,4-disubstituted quinazolines via Grob fragmentation.
Subject(s)
Benzodiazepinones/chemical synthesis , Nitriles/chemistry , Organometallic Compounds/chemistry , Benzodiazepinones/chemistry , Molecular Structure , StereoisomerismABSTRACT
A series of thio- and selenopyrans having two fused indole units, structurally related to indolocarbazoles, have been prepared and evaluated for aryl hydrocarbon receptor (AhR) affinity, leading to the identification of several new significant AhR ligands. In particular, the parent thiopyrano[2,3-b:6,5-b']diindole and its derivative having a methyl group in the central ring, as well as the two corresponding selenopyrans, displayed the highest potencies of the compounds tested.
Subject(s)
Indoles/chemistry , Organoselenium Compounds/chemistry , Pyrans/chemistry , Receptors, Aryl Hydrocarbon/chemistry , Sulfhydryl Compounds/chemistry , Animals , Carbazoles/chemistry , Cell Line, Tumor , Guinea Pigs , Humans , Indoles/chemical synthesis , Indoles/metabolism , Indoles/pharmacology , Molecular Structure , Organoselenium Compounds/chemical synthesis , Organoselenium Compounds/metabolism , Organoselenium Compounds/pharmacology , Pyrans/chemical synthesis , Pyrans/metabolism , Pyrans/pharmacology , Receptors, Aryl Hydrocarbon/metabolism , Structure-Activity Relationship , Sulfhydryl Compounds/chemical synthesis , Sulfhydryl Compounds/metabolism , Sulfhydryl Compounds/pharmacologyABSTRACT
A synthesis of the originally proposed 2-(1 H-indol-3-yl)-4 H-3,1-benzoxazin-4-one structure of the alkaloid cephalandole A (1) led to a structural revision, and the isolated natural product has now been identified as the previously known compound 3-(1 H-indol-3-yl)-2 H-1,4-benzoxazin-2-one (7). The structural assignment was corroborated by detailed NMR studies. A short synthesis of the related natural compound cephalandole B (2) has also been performed, confirming its structure. In addition some chemical transformations, involving, for example, the related synthetic molecule 2-(1 H-indol-3-yl)-3 H-quinazolin-4-one (9), are presented.
Subject(s)
Alkaloids/chemical synthesis , Benzoxazines/chemical synthesis , Indoles/chemical synthesis , Orchidaceae/chemistry , Alkaloids/chemistry , Benzoxazines/chemistry , Chromatography, High Pressure Liquid , Indoles/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrophotometry, InfraredABSTRACT
Reactivation of mutant p53 has emerged as a promising approach for cancer therapy. Recent studies have identified several mutant p53-reactivating compounds that target thiol groups in mutant p53. Here we have investigated the relationship between thiol reactivity, p53 thermostabilization, mutant p53 refolding, mutant p53-dependent growth suppression, and induction of cell death. Analysis of the National Cancer Institute database revealed that Michael acceptors show the highest selectivity for mutant p53-expressing cells among analyzed thiol-reactive compounds. Further experimental testing demonstrated that Michael acceptors, aldehydes, imines, and primary alcohols can promote thermodynamic stabilization of mutant p53. Moreover, mild thiol reactivity, often coupled with combined chemical functional groups, such as in imines, aldehydes, and primary alcohols, can stimulate mutant p53 refolding. However, strong electrophile activity was associated with cellular toxicity. Our findings may open possibilities for rational design of novel potent and selective mutant p53-reactivating compounds.
Subject(s)
Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Point Mutation , Sulfhydryl Compounds/metabolism , Tumor Suppressor Protein p53/genetics , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Models, Molecular , Neoplasms/genetics , Neoplasms/metabolism , Point Mutation/drug effects , Protein Refolding/drug effects , Protein Stability/drug effects , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolismABSTRACT
Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs. We demonstrate here that the mutant p53-reactivating compound PRIMA-1(MET) acts synergistically with several chemotherapeutic drugs to inhibit tumor cell growth. Combined treatment with cisplatin and PRIMA-1(MET) resulted in a synergistic induction of tumor cell apoptosis and inhibition of human tumor xenograft growth in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic drugs is likely to increase the sensitivity of tumor cells to PRIMA-1(MET). Thus, the combination of PRIMA-1(MET) with currently used chemotherapeutic drugs may represent a novel and more efficient therapeutic strategy for treatment of mutant p53-carrying tumors.
Subject(s)
Adenocarcinoma/pathology , Apoptosis/drug effects , Aza Compounds/pharmacology , Bone Neoplasms/pathology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/pharmacology , Genes, p53 , Lung Neoplasms/pathology , Osteosarcoma/pathology , Quinuclidines/pharmacology , Animals , Drug Interactions , Drug Resistance, Neoplasm , Humans , Mice , Mice, SCID , Mutation , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
Barettin (cyclo [(6-bromo-8-en-tryptophan) arginine]), a diketopiperazine isolated from the marine sponge Geodia barretti, is a potent inhibitor of barnacle larvae settlement with an EC50-value of 0.9 microM. In the present study, 14 analogs of barettin and its structural congener dipodazine were synthezised and tested for their ability to inhibit larval settlement. Two of the analogs have an intact barettin skeleton. The remaining analogs have a dipodazine skeleton (a diketopiperazine where arginine is replaced with glycine). Six of the tested synthetic analogs displayed significant settlement inhibition with the most potent inhibitor being benzo[g]dipodazine, which displayed even stronger activity than barettin (EC50-value 0.034 microM). The effect of benzo[g]dipodazine was also shown to be readily reversible, when cyprids were transferred to filtered seawater (FSW).
Subject(s)
Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Porifera/chemistry , Animals , Diketopiperazines , Glycine/chemical synthesis , Glycine/chemistry , Indoles/chemical synthesis , Indoles/chemistry , Indoles/pharmacology , Larva/cytology , Larva/drug effects , Larva/metabolism , Peptides, Cyclic/chemical synthesis , Piperazines/chemical synthesis , Piperazines/chemistry , Piperazines/pharmacology , Porifera/cytology , Porifera/metabolism , Stereoisomerism , Structure-Activity Relationship , Thoracica/cytology , Thoracica/drug effectsABSTRACT
5,6,11,12,17,18-Hexahydrocyclonona[1,2-b:4,5-b*:7,8-b**]triindole (CTr) is a major digestive product of indole-3-carbinol (I3C) from Brassica vegetables and exhibits strong estrogenic activities. CTr increases proliferation of estrogen-dependent breast tumor cells, binds with strong affinity for the estrogen receptor-alpha (ERalpha), and activates expression of estrogen (E(2))-dependent genes. To begin to examine the structural features that determine the biological activity of CTr, we prepared and studied the effects of two analogs, 9,18-dihydro-12H-[1,2,5]trithionino[3,4-b:6,7-b*:9,8-b**]triindole (S(3)CTr) and 5,6,11,12,17,18-hexahydro-5,11,17-trimethylcyclonona[1,2-b:4,5-b*:7,8-b**]triindole (Me(3)CTr). N-Methylation of CTr completely ablated the estrogenic activities of CTr. In the dose range in which CTr was clearly estrogenic, Me(3)CTr exhibited no detectable effect on cell growth, ERalpha binding to E(2), or ERalpha-responsive gene expression. S(3)CTr showed mixed ERalpha agonist activities. It bound to the ERalpha and activated receptor binding with DNA, weakly activated expression of transfected E(2)-responsive reporter gene constructs, and strongly inhibited the E(2)-induced activation of these reporter constructs. S(3)CTr activated aryl hydrocarbon receptor (AhR)-mediated pathways, consistent with the moderately strong binding affinity of S(3)CTr for the AhR. Comparisons of the conformational characteristics among CTr and its two analogs indicated that the estrogenic effects of CTr are highly sensitive to apparently minor structural modifications, and further supported the hypothesis for a central role of hydrogen bonding around the nitrogen atom in CTr binding to the ligand binding site of ERalpha.
Subject(s)
Breast Neoplasms/drug therapy , Estrogen Antagonists/pharmacology , Estrogen Receptor alpha/metabolism , Indoles/pharmacology , Neoplasms, Hormone-Dependent/drug therapy , Animals , Binding, Competitive/physiology , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cytochrome P-450 CYP1A1/metabolism , DNA, Neoplasm/chemistry , DNA, Neoplasm/genetics , Electrophoretic Mobility Shift Assay , Female , Humans , Indoles/chemistry , Mice , Models, Molecular , Neoplasms, Hormone-Dependent/enzymology , Neoplasms, Hormone-Dependent/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Structure-Activity Relationship , TransfectionABSTRACT
Tellurium tetrachloride and allylphenyl sulfide react to form (1-thia-2-tellura-1-phenyl-4-chloro)cyclopentane 2,2,2-trichloride. The crystal and molecular structure were determined by single-crystal X-ray techniques. The crystals belong to the monoclinic system, space group P2(1)/c (No. 14) with a = 6.020(3) Å, b = 11.46(1) Å, c = 20.156(2) Å, beta = 97.53(2) degrees, V = 1379(1) Å(3), and Z = 4. The structure was refined to the final R value of 0.036. The coordination around Te(IV) is distorted psi octahedral with three Cl atoms in the equatorial positions. The axial Te(1)-C(1) bond opposite to the lone pair of electrons at the Te(IV) atom completes the coordination polyhedron. The intramolecular Te-S distance is 2.903(3) Å. Symmetric and asymmetric deformation modes were established to describe the plasticity of the Cl-Te-Cl fragments extracted from the Cambridge Structural Database. The hypervalency of Te(IV) manifests itself as plasticity in the equatorial plane of the coordination sphere. The NBO calculations show that all of the equatorial Te-Cl bonds are highly polarized and the electrons reside mainly on the Cl atoms.