RESUMO
Recently a new di-gold(I) organometallic complex [1,3-(Ph(3)PAu)(2)-C(6)H(4)] (KF0101) has been synthesised and found to exhibit cytotoxic activity in vitro. Subsequently it has been demonstrated that KF0101 shows little or no cross-resistance against a number of the cisplatin resistant ovarian cancer cell lines in vitro suggesting a different mode of action for the drug. In this study, syncrotron radiation infrared microspectroscopy (SR-IRMS) has been used on drug treated single A2780 cells in order to determine if this different mode of action can be identified spectroscopically. The aim of the study was to establish: (i) if single cell SR-IRMS could be used to give insight into the cellular response on treatment with different cytotoxic agents relative to non-treated cells (control) and (ii) that if the cytotoxic drugs elicit a different biochemical response these responses could be distinguished from each other. The most striking features obtained after Principal Components Analysis (PCA) of Resonant Mie Scattering (RMieS) corrected single cell spectra of drug treated ovarian A2780 cells are: (i) The spectra obtained for the control are quite heterogeneous and several hundred spectra are required to adequately define the nature of the control; (ii) after drug treatment at the IC50 level for 24 h with cisplatin, KF0101, methotrexate, paclitaxel or 5-fluorouracil the cell spectra, as represented on a PCA scores plot, generally concentrate in certain well defined areas of the control, there are however a small number of spectra that fall outside of the area defined by the control; and (iii) a differentiation between cell spectra obtained on treatment with different drugs is observed which fits well with different in vitro cell culture behaviour and a flow cytometry cell cycle analysis of the control and drug treated cells. Inspection of the loading plots shows that PC1 is essentially the same for all plots and reflects changes in cell biochemistry related to the cell cycle. PC2, however, on comparison of the control versus cisplatin or cisplatin versus KF0101 is indicative of differences induced by drug treatment and has been termed as cell cycle-plus behaviour. These data are shown to be consistent with that obtained using bench-top IRMS by averaging a number of single cell spectra and carrying out a PCA, but SR-IRMS offers more insight into how the drug is affecting the cell population. More importantly, this approach enables the influence of the cell cycle on both the control and drug treated samples to be taken into consideration when evaluating the drug-cell interaction.
Assuntos
Antineoplásicos/farmacologia , Análise de Célula Única/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Síncrotrons , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Concentração Inibidora 50 , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Análise de Componente Principal , Análise de Célula Única/instrumentação , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentaçãoRESUMO
The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC(50) 0.21nM; combretastatin A4 CA4, IC(50) 2.0nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC(50) 0.46microM; CA4, 0.10microM) and compete with [(3)H]colchicine for binding to tubulin (8% [(3)H]colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity.
Assuntos
Antineoplásicos/síntese química , Bibenzilas/farmacologia , Proliferação de Células/efeitos dos fármacos , Chalconas/farmacologia , Microtúbulos/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Moduladores de Tubulina/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Bibenzilas/síntese química , Bibenzilas/química , Linhagem Celular Tumoral , Chalconas/síntese química , Chalconas/química , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Microtúbulos/metabolismo , Relação Estrutura-Atividade , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologiaRESUMO
PURPOSE: The purpose of our study was to investigate the cellular accumulation, DNA cross-linking ability, and cellular toxicity of RH1 (2,5-diaziridinyl-3-[hydroxymethyl[-6-methyl-1,4-benzoquinone), a novel DNA alkylating agent currently in clinical trials. In addition, the in vivo efficacy of RH1 formulated in different vehicles was also compared. EXPERIMENTAL DESIGN: RH1 is activated by the two-electron reducing enzyme NQO1 [NADPH:quinone oxidoreductase] forming a potent cytotoxic agent that cross-links DNA. We have used whole blood, cell lines, and primary explanted tumor cultures to measure both the cellular accumulation, DNA cross-linking, and cytotoxicity of RH1. Furthermore, the pharmacokinetic and pharmacodynamic characteristics of RH1 formulated in different vehicles were measured in vivo using the validated comet-X assay in mice bearing human tumor xenografts. RESULTS: Accumulation of RH1 was shown to be both time and concentration dependent, reaching a maximum after 2 hours and correlated well with DNA cross-linking measurements. DNA cross-linking in vitro could be detected at low (1-10 nmol/L) concentrations after as little as 2 hours exposure. In primary tumor cultures, RH1 induces much higher levels of DNA cross-links at lower doses than either mitomycin C or cisplatin. In vivo efficacy testing using polyvinyl pyrrolidone, saline, or cyclodextrin as vehicles showed DNA cross-links readily detectable in all tissues examined and was enhanced when given in cyclodextrin compared with polyvinyl pyrrolidone or saline. CONCLUSIONS: RH1 represents a potent bioreductive anticancer drug, which may prove effective in the treatment of cancers, particularly those that overexpress NQO1. DNA cross-linking can be reliably measured in tissue using the validated comet-X assay.
Assuntos
Aziridinas/farmacologia , Benzoquinonas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Aziridinas/sangue , Aziridinas/farmacocinética , Benzoquinonas/sangue , Benzoquinonas/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaio Cometa/métodos , Reagentes de Ligações Cruzadas/farmacologia , DNA/química , DNA/genética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Camundongos , Camundongos Nus , Resultado do Tratamento , TrítioRESUMO
BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.
Assuntos
Neoplasias Pulmonares/prevenção & controle , Neovascularização Patológica/prevenção & controle , Neovascularização Fisiológica/efeitos dos fármacos , Oligossacarídeos/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Anticoagulantes/farmacologia , Linhagem Celular Tumoral , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacologia , Heparina/química , Heparina/farmacologia , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Tempo de Tromboplastina Parcial , Ensaios Antitumorais Modelo de Xenoenxerto/instrumentação , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. METHODS: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 (0.3, 1, 3, or 10 mg/kg). Positron emission tomography with (124)I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (k(fp)) to determine tumor vascular permeability. RESULTS: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic endpoints could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumors. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in k(fp) 48 hours after the first treatment (median = 44%; range = 4%-91%). CONCLUSIONS: Because of the heterogeneity in tumor biology with respect to antibody uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with antiangiogenic compounds like HuMV833.
Assuntos
Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Fatores de Crescimento Endotelial/imunologia , Linfocinas/imunologia , Imageamento por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Neovascularização Patológica/fisiopatologia , Animais , Anticorpos Monoclonais Humanizados , Formação de Anticorpos , Permeabilidade Capilar , Relação Dose-Resposta Imunológica , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Fatores de Crescimento Endotelial/metabolismo , Humanos , Radioisótopos do Iodo , Linfocinas/metabolismo , Macaca fascicularis/imunologia , Dose Máxima Tolerável , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neoplasias/irrigação sanguínea , Neoplasias/imunologia , Distribuição Tecidual , Tomografia Computadorizada de Emissão , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The development of combretastatin as an antimitotic agent has led to an enormous effort to design other tubulin-targeting agents. The intriguing discovery that combretastatin A-4 phosphate causes selective damage to tumor vasculature has stimulated even more activity in this field. This attention to tubulin binding agents and their antivasculature activity is highly likely to lead to significant clinical advances for the treatment of cancer. This review focuses on the development of ketones as tubulin-binding agents such as chalcones and related enones as surrogates of combretastatin and colchicine.
Assuntos
Antineoplásicos/química , Chalcona/química , Antineoplásicos/farmacologia , Benzofenonas/química , Chalcona/farmacologia , Colchicina/química , Cristalização , Desenho de Fármacos , Flavonas/química , Tubulina (Proteína)/metabolismo , Difração de Raios XRESUMO
PURPOSE: Heparan sulfate proteoglycans have been implicated in cancer cell growth, invasion, metastasis, and angiogenesis. This study was designed to compare their expression in normal ovary and ovarian tumors and then to examine their prognostic significance in ovarian cancer. EXPERIMENTAL DESIGN: The expression of syndecan-1, -2, -3, and -4, glypican-1, and perlecan was assessed by immunohistochemistry in 147 biopsies that included normal ovary and benign, borderline, and malignant ovarian tumors. Clinical data, including tumor stage, performance status, treatment, and survival, were collected. Univariate and multivariate analyses were performed to evaluate prognostic significance. RESULTS: The expression patterns of syndecan-1 and perlecan were altered in ovarian tumors compared with normal ovary. Syndecan-1 was not detected in normal ovary but was present in the epithelial and stromal cells of benign and borderline tumors and in ovarian adenocarcinomas. Perlecan expression was decreased in basement membranes that were disrupted by cancer cells but maintained in the basement membranes of blood vessels. Syndecan-2, -3, and -4, and glypican-1 were expressed in normal ovary and benign and malignant ovarian tumors. Stromal expression of syndecan-1 and glypican-1 were poor prognostic factors for survival in univariate analysis. CONCLUSION: We report for the first time distinct patterns of expression of cell surface and extracellular matrix heparan sulfate proteoglycans in normal ovary compared with ovarian tumors. These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy.
Assuntos
Proteoglicanas de Heparan Sulfato/metabolismo , Neoplasias Ovarianas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Intervalo Livre de Doença , Matriz Extracelular/metabolismo , Feminino , Proteoglicanas de Heparan Sulfato/biossíntese , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia , Prognóstico , Proteoglicanas/biossíntese , Sindecana-1 , Sindecana-2 , Sindecana-3 , Sindecana-4 , Sindecanas , Fatores de Tempo , Resultado do TratamentoRESUMO
A series of combretastatins substituted with epoxides, amides and small alkyl groups has been synthesised and evaluated for cytotoxicity and their ability to inhibit the assembly of tubulin. The methyl and ethyl substituted phenols 36, 44 have shown potent antimitotic effects whilst exhibiting reduced cytotoxicity.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Bibenzilas/síntese química , Bibenzilas/farmacologia , Estilbenos/síntese química , Estilbenos/farmacologia , Amidas/síntese química , Amidas/química , Amidas/farmacologia , Antineoplásicos/química , Bibenzilas/química , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Formazans/química , Humanos , Concentração Inibidora 50 , Células K562 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrofotometria Ultravioleta , Estilbenos/química , Sais de Tetrazólio/química , Tubulina (Proteína)/metabolismo , Moduladores de TubulinaRESUMO
To investigate within live mammalian cells the uptake and disposition of combretastatins, fluorescence lifetime imaging was used with two-photon excitation (2PE). Combretastatin A4 (CA4) and analogues are potential anticancer drugs due to their ability to inhibit angiogenesis. E(trans)-combretastatins are considerably less active than the Z(cis)-combretastatins proposed for clinical use. However the E-combretastatins exhibit stronger intrinsic fluorescence with quantum yields and lifetimes that depend markedly on solvent polarity and viscosity. It is proposed that 2PE in the red and near-infrared tissue window may allow in situ isomerization of E-combretastatins to the more active Z-isomer, offering spatial and temporal control of drug activation and constitute a novel form of photodynamic therapy. In the present work we have characterised 2PE of E-CA4 and have used fluorescence lifetime imaging with 2PE to study uptake and intracellular disposition of E-CA4 and an analogue. The results show that these molecules accumulate rapidly in cells and are located mainly in lipidic environments such as lipid droplets. Within the droplets the local concentrations may be up to two orders of magnitude higher than that of the drug in the surrounding medium.
Assuntos
Bibenzilas/farmacocinética , Microscopia de Fluorescência por Excitação Multifotônica , Estilbenos/farmacocinética , Animais , Bibenzilas/química , Células CHO , Cricetinae , Células HeLa , Humanos , Estilbenos/químicaRESUMO
The tyrosine kinase inhibitor imatinib (STI 571; glivec) is a potent inhibitor of bcr-abl, c-kit and platelet-derived growth factor receptors. Imatinib was evaluated both alone and in combination with established chemotherapeutic agents in adenoid cystic carcinoma (ACC) primary cultures and established cell lines representing squamous cell carcinoma of the head and neck (HNSCC). Over 90% of ACC tumors are c-kit-positive, and these primary cultures proved to be of short-term usefulness in assessing chemosensitivity. Interaction was determined over a wide range of drug combinations using a statistical three-dimensional analysis model. Both ACC short-term cultures and HNSCC cell lines were demonstrated to have a response ranging from additive to synergistic when imatinib and cisplatin were combined. The interaction of imatinib on cisplatin-induced DNA cross-linking was further investigated using the comet-X assay. In contrast, significant antagonism was observed when imatinib and gemcitabine were combined. Since gemcitabine is activated by deoxycytidine kinase (dCK), the effect of imatinib on this enzyme was investigated. A dose-dependent inhibition of dCK was observed, highlighting this kinase as a possible additional secondary molecular target for imatinib. This work demonstrates a synergistic interaction between cisplatin and imatinib, which may prove to be clinically relevant in the future management of both ACC and HNSCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Ensaio Cometa , Antagonismo de Drogas , Sinergismo Farmacológico , Humanos , Mesilato de Imatinib , Concentração Inibidora 50 , Piperazinas/administração & dosagem , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/administração & dosagemRESUMO
A series of combretastatins possessing both a trimethoxy unit and other substituents on ring A has been synthesised and tested for cytotoxicity and their ability to interact with the protein tubulin. All previous studies have indicated that the trimethoxy unit is essential for interaction with tubulin. The studies herein show that molecules possessing functionalities other than trimethoxy can also interact with tubulin. Importantly a trimethyl substituted agent 52a has shown reduced cytotoxicity, but increased potency in its ability to inhibit the assembly of tubulin.
Assuntos
Antineoplásicos/química , Bibenzilas/química , Estilbenos/química , Tubulina (Proteína)/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Bibenzilas/farmacologia , Linhagem Celular , Chlorocebus aethiops , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imuno-Histoquímica , Concentração Inibidora 50 , Células K562 , Estrutura Molecular , Estilbenos/análise , Estilbenos/síntese química , Estilbenos/farmacologia , Relação Estrutura-Atividade , Células VeroRESUMO
The naturally occurring aurone 1, isolated from Uvaria hamiltonii, and a series of aurones analogues based structurally on known tubulin binding agents were prepared and evaluated for anticancer activity. Aurone 20 was the most active (IC(50) K562 50 nM) and caused significant G2/M cell-cycle arrest.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Benzofuranos/síntese química , Benzofuranos/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Uvaria/química , Antineoplásicos Fitogênicos/isolamento & purificação , Benzofuranos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , DNA de Neoplasias/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Humanos , Indicadores e Reagentes , Células K562 , Mitose/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Relação Estrutura-Atividade , Sais de Tetrazólio , Tiazóis , Tubulina (Proteína)/efeitos dos fármacos , Tubulina (Proteína)/metabolismoRESUMO
Microtubules are intracellular organelles formed from the protein tubulin. These organelles have a number of essential cellular functions including chromosome segregation, the maintenance of cell shape, transport, motility, and organelle distribution. Drugs that affect the tubulin-microtubule equilibrium (taxol, vinca alkaloids) are effective anticancer drugs. This review describes the molecular target, methods used in screening, the structures of compounds known to interact with tubulin, and the clinical use of these agents. In addition the ability of these agents to destroy tumour vasculature is described. This represents an exciting new molecular target in the design of anticancer drugs.
Assuntos
Antineoplásicos/farmacologia , Microtúbulos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Moduladores de Tubulina , Animais , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/fisiologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Microtúbulos/metabolismo , Conformação Molecular , Neoplasias/metabolismo , Neoplasias/fisiopatologia , Taxoides/farmacologia , Tubulina (Proteína)/metabolismo , Alcaloides de Vinca/farmacologiaRESUMO
The organomercurial compounds Hg[1-C(6)H(4)-2-C(H)=NC(6)H(5-n)R(n)](2) (R = 4-NMe(2), 6a; 4-Me, 6b; 4-I, 6c; 4-NO(2), 6d; 2-(i)Pr, 6e; 2-Me, 6f; 2,6-(i)Pr(2), 6g; 2,6-Me(2), 6h) have been prepared in good overall yield from 2-bromobenzaldehyde. All of the compounds have been characterized by elemental analysis, (1)H NMR, (13)C[(1)H] NMR, and infrared spectroscopy. In addition, compounds 6a [C(30)H(30)HgN(4), triclinic, P, a = 6.20000(10) A, b = 9.2315(2) A, c = 10.9069(3) A, alpha = 85.8510(10) degrees, beta = 89.3570(10) degrees, gamma = 87.206(2) degrees, Z = 1], 6b [C(28)H(24)HgN(2), monoclinic, P2(1)/c, a = 12.8260(5) A, b = 14.0675(4) A, c = 6.1032(2) A, beta = 90.0990(10) degrees, Z = 2], 6g [C(38)H(44)HgN(2), triclinic, P, a = 8.2626(2) A, b = 9.8317(2) A, c = 11.8873(3) A, alpha = 103.6650(10) degrees, beta = 109.3350(10) degrees, gamma = 104.627(2) degrees, Z = 1], and 6h [C(30)H(28)HgN(2), monoclinic, P2(1)/c, a = 12.5307(2) A, b = 10.9852(2) A, c = 18.2112(2) A, beta = 104.0190(10) degrees, gamma = 87.206(2) degrees, Z = 4] have been characterized by low-temperature single-crystal X-ray diffraction studies, and two different molecular geometries about the central mercury atom have been observed; intramolecular contacts suggest a van der Waals radius for Hg of 2.1-2.2 A.