Crystal structures and hydrogen-bonding analysis of a series of benzamide complexes of zinc(II) chloride.

Ionic co-crystals are co-crystals between organic mol-ecules and inorganic salt coformers. Co-crystals of pharmaceuticals are of inter-est to help control polymorph formation and potentially improve stability and other physical properties. We describe the preparation, crystal structures, and hydrogen bonding of five different 2:1 benzamide or tolu-amide/zinc(II) chloride co-crystal salts, namely, bis-(benzamide-κO)di-chlorido-zinc(II), [ZnCl2(C7H7NO)2], di-chlor-ido-bis-(2-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], di-chlorido-bis-(3-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], di-chlorido-bis-(4-methyl-benzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], and di-chlorido-bis-(4-hy-droxy-benzamide-κO)zinc(II), [ZnCl2(C7H7NO2)2]. All of the complexes contain hydrogen bonds between the amide N-H group and the amide carbonyl oxygen atoms or the chlorine atoms, forming extended networks.

Teaching Cheminformatics through a Collaborative Intercollegiate Online Chemistry Course (OLCC).

While cheminformatics skills necessary for dealing with an ever-increasing amount of chemical information are considered important for students pursuing STEM careers in the age of big data, many schools do not offer a cheminformatics course or alternative training opportunities. This paper presents the Cheminformatics Online Chemistry Course (OLCC), which is organized and run by the Committee on Computers in Chemical Education (CCCE) of the American Chemical Society (ACS)'s Division of Chemical Education (CHED). The Cheminformatics OLCC is a highly collaborative teaching project involving instructors at multiple schools who teamed up with external chemical information experts recruited across sectors, including government and industry. From 2015 to 2019, three Cheminformatics OLCCs were offered. In each program, the instructors at participating schools would meet face-to-face with the students of a class, while external content experts engaged through online discussions across campuses with both the instructors and students. All the material created in the course has been made available at the open education repositories of LibreTexts and CCCE Web sites for other institutions to adapt to their future needs.

Bis(2,4-dioxo-pentan-3-ido-κ2 O,O')dioxidomolyb-denum(VI): a redetermination.

The title compound, [Mo(C5H7O2)2O2] or cis-[MoO2(acac)2] (acac is acetyl-acetonate), contains a molybdenum(VI) atom coordinated by two acetyl-acetonate ligands and two doubly bonded oxido ligands in a distorted octa-hedral shape. The mol-ecule is chiral and the asymmetric unit contains two independent mol-ecules (one Δ, one Λ). Extensive C-H⋯O contacts are present throughout the structure. Data were collected at 100 K, providing higher precision of unit-cell parameters and atomic positions than previous determinations [Kamenar et al. (1973 ▸). Cryst. Struct. Commun. 2, 41-44.; Krasochka et al. (1975). Zh. Strukt. Khim. 16, 696-698].

Crystal structures and hydrogen-bonding analysis of a series of solvated ammonium salts of molybdenum(II) chloride clusters.

Charge-assisted hydrogen bonding plays a significant role in the crystal structures of solvates of ionic com-pounds, especially when the cation or cations are primary ammonium salts. We report the crystal structures of four ammonium salts of molybdenum halide cluster solvates where we observe significant hydrogen bonding between the solvent molecules and cations. The crystal structures of bis-(anilinium) octa-µ3-chlorido-hexa-chlorido-octa-hedro-hexa-molybdate N,N-di--methyl-formamide tetra-solvate, (C6H8N)2[Mo6Cl8Cl6]·4C3H7NO, (I), p-phenyl-enedi-ammonium octa-µ3-chlorido-hexa-chlorido-octa-hedro-hexa-mol-yb-date N,N-di-methyl-formamide hexa-solvate, (C6H10N2)[Mo6Cl8Cl6]·6C3H7NO, (II), N,N'-(1,4-phenyl-ene)bis-(propan-2-iminium) octa-µ3-chlorido-hexa-chlo-rido-octa-hedro-hexa-molybdate acetone tris-olvate, (C12H18N2)[Mo6Cl8Cl6]·3C3H6O, (III), and 1,1'-dimethyl-4,4'-bipyridinium octa-µ3-chlo-rido-hexa-chlorido-octa-hedro-hexa-molybdate N,N-di-methyl-formamide tetra-solvate, (C12H14N2)[Mo6Cl8Cl6]·4C3H7NO, (IV), are reported and described. In (I), the anilinium cations and N,N-di-methyl-formamide (DMF) solvent mol-ecules form a cyclic R 4 2(8) hydrogen-bonded motif centered on a crystallographic inversion center with an additional DMF mol-ecule forming a D(2) inter-action. The p-phenyl-enedi-ammonium cation in (II) forms three D(2) inter-actions between the three N-H bonds and three independent N,N-di-methyl-formamide mol-ecules. The dication in (III) is a protonated Schiff base solvated by acetone mol-ecules. Compound (IV) contains a methyl viologen dication with N,N-di-methyl-formamide mol-ecules forming close contacts with both aromatic and methyl H atoms.

Multiple breast cancer cell-lines derived from a single tumor differ in their molecular characteristics and tumorigenic potential.

BACKGROUND: Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient's breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. METHODS: Five breast cancer cell lines were derived from a single patient's primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER), CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC). In addition, a Fluorescent In Situ Hybridization (FISH) assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. RESULTS: We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. CONCLUSIONS: All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to identify mechanisms of organ-specific metastasis of breast cancer.

cis-Diamminedichloridoplatinum(II) N,N-dimethyl-formamide monosolvate.

In the title compound, cis-[PtCl2(NH3)2]·C3H7NO, the metal complex mol-ecules are stacked parallel to the b axis, forming close Pt⋯Pt inter-actions of 3.4071 (7) and 3.5534 (8) Šand weak N-H⋯Cl hydrogen bonds between the ammine ligand and the Cl atoms of the neighboring complex. Conventional N-H⋯O hydrogen bonds are formed between ammine ligands and the O atom of adjacent N,N-dimethyl-formamide mol-ecules. The crystal was found to be a split crystal and was analyzed using two domains related by a rotation of ca 4.4° about the reciprocal axis (-0.351 1.000 0.742) and refined to give a minor component fraction of 0.084 (6).

Tris(3-nitro-pentane-2,4-dionato-κO,O')-cobalt(III).

The structure of the title compound, [Co(C(5)H(6)NO(4))(3)], consists of a Co(III) ion octahedrally coordinated by three bidentate 3-nitro-pentane-2,4-dionate ligands. The complex was prepared via the nitration of tris-(2,4-penta-nedionato-κ(2)O,O')cobalt(III) with a solution of copper(II) nitrate in glacial acetic acid. The central C atom and the nitro group of one 3-nitro-pentane-2,4-dionate ligand are disordered over two positions with an occupancy ratio of 0.848 (4):0.152 (4). A second nitro group is also disordered over two orientations with an occupancy ratio of 0.892 (7):0.108 (7). Two of the ligand methyl groups form C-H⋯O inter-actions with two different nitro groups to form chains running along the c axis. Additional C-H⋯O inter-actions are found between ligand methyl groups and the cobalt-bound O atoms, also resulting in the formation of chains along the c axis.

2,5-Dimethyl-1,3-dinitro-benzene.

The title compound, C(8)H(8)N(2)O(4), was prepared via the nitration of p-xylene. The mol-ecules are stacked along the c axis in an antiparallel manner. The two nitro groups are rotated relative to the benzene ring with dihedral angles of 44.50 (7) and 31.67 (8)°. The tilt of the nitro groups allows the formation of C-H⋯O inter-actions between the ring C-H and nitro groups of adjacent mol-ecules creating puckered sheets perpendicular to the c axis. The H atoms of the methyl group in the 5-position are disordered (60° rotation) with an occupancy of 0.616 (19) for the major component. The crystal was found to be a non-merohedral twin with a twin law [-1 -0.002 0.005, 0.00031 -1 0.002, 0.118 -0.007 1] corresponding to a rotation of 180° about the reciprocal axis (001) and refined to give a minor component fraction of 0.320 (2).

4-Nitro-N-(3-nitro-phen-yl)benzamide.

The title compound, C(13)H(9)N(3)O(5), prepared as a solid derivative of 3-nitro-analine via reaction with 4-nitro-benzoyl chloride, crystallizes in a chiral space group. The mol-ecule is non-planar with a dihedral angle of 26.1 (1)° between the two benzene rings. Both nitro groups are twisted slightly out of the plane of their corresponding benzene rings, making dihedral angles of 10.7 (4) and 13.5 (4)°. The mol-ecules are stacked along the a axis with benzene ring centroid-centroid distances of 3.8878 (6) Å. In the crystal, inter-molecular benzene C-H⋯O inter-actions involving one nitro group and the carbonyl group link the mol-ecules, forming chains along [001]. An additional set of aromatic C-H⋯O inter-actions with the second nitro group form chains along [101], connecting adjacent chains to create layers perpendicular to the b axis.

A low-temperature phase of bis(tetrabutylammonium) octa-µ(3)-chlorido-hexachlorido-octahedro-hexatungstate.

The title compound, (C(16)H(36)N)(2)[W(6)Cl(14)], undergoes a reversible phase transition at 268 (1) K. The structure at 150 and 200 K has monoclinic (P2(1)/c) symmetry. Both crystallographically independent tungsten chloride cluster anions sit on crystallographic inversion centers [symmetry codes: (-x, -y + 1, -z) and (-x + 1, -y + 2, -z)]. Two previous studies at room temperature describe the structure in the space group P2(1)/n with a unit-cell volume approximately half the size of the low-temperature unit cell [Zietlow, Schaefer et al. (1986). Inorg. Chem. 25, 2195-2198; Venkataraman et al. (1999). Inorg. Chem. 38, 828-830]. The unit cells of the room- and low-temperature polymorphs are closely related. The hydrocarbon chain of one of the tetrabutylammonium cations is disordered at both 150 and 200 K.

Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod.

Plasmodium sporozoites injected into the skin by malaria-infected mosquitoes can be effectively targeted by antibodies that block parasite invasion of host hepatocytes and thus prevent the subsequent development of blood stage infections responsible for clinical disease. Malaria subunit vaccines require potent adjuvants, as they lack known pathogen-associated molecular patterns found in attenuated viral or bacterial vaccines that function as Toll-like receptor (TLR) agonists to stimulate dendritic cells and initiate strong adaptive immune responses. A synthetic TLR7 agonist, imiquimod, which is FDA approved for topical treatment of various skin conditions, can function as a potent adjuvant for eliciting T-cell responses to intracellular pathogens and model protein antigens. In the current studies, the topical application of imiquimod at the site of subcutaneously injected Plasmodium falciparum circumsporozoite (CS) peptides elicited strong parasite-specific humoral immunity that protected against challenge with transgenic rodent parasites that express P. falciparum CS repeats. In addition, injection of a simple linear peptide followed by topical imiquimod elicited strong Th1 CD4(+) T-cell responses, as well as high antibody titers. The correlation of high anti-repeat antibody titers with resistance to sporozoite challenge in vivo and in vitro supports use of this topical TLR7 agonist adjuvant to elicit protective humoral immunity. The safety, simplicity, and economic advantages of a topical synthetic TLR7 agonist adjuvant also apply to other vaccines requiring high antibody titers, such as malaria asexual or sexual blood stage antigens to prevent red blood cell invasion and block transmission to the mosquito vector, and to vaccines to other extracellular pathogens.

TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines.

Cancer vaccines, while theoretically attractive, present difficult challenges that must be overcome to be effective. Cancer vaccines are often poorly immunogenic and may require augmentation of immunogenicity through the use of adjuvants and/or immune response modifiers. Toll-like receptor (TLR) ligands are a relatively new class of immune response modifiers that may have great potential in inducing and augmenting both cellular and humoral immunity to vaccines. TLR7 ligands produce strong cellular responses and specific IgG2a and IgG2b antibody responses to protein immunogens. This study shows that a new TLR7 ligand, 3M-019, in combination with liposomes produces very strong immune responses to a pure protein prototype vaccine in mice. Female C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1 mg/dose) weekly 4x. Some groups were immunized to OVA plus 3M-019 or to OVA plus 3M-019 encapsulated in liposomes. Both antibody and cellular immune responses against OVA were measured after either two or four immunizations. Anti-OVA IgG antibody responses were significantly increased after two immunizations and were substantially higher after four immunizations in mice immunized with OVA combined with 3M-019. Encapsulation in liposomes further augmented antibody responses. IgM responses, on the other hand, were lowered by 3M-019. OVA-specific IgG2a levels were increased 625-fold by 3M-019 in liposomes compared to OVA alone, while anti-OVA IgG2b levels were over 3,000 times higher. In both cases encapsulation of 3M-019 in liposomes was stronger than either liposomes alone or 3M-019 without liposomes. Cellular immune responses were likewise increased by 3M-019 but further enhanced when it was encapsulated in liposomes. The lack of toxicity also indicates that this combination may by safe, effective method to boost immune response to cancer vaccines.

Reduction in IV t-PA door to needle times using an Acute Stroke Triage Pathway.

OBJECTIVE: To determine the effectiveness of an Acute Stroke Triage Pathway in reducing door to needle times in acute stroke treatment with IV t-PA. BACKGROUND: A previous study at our tertiary referral centre, examining IV t-PA door to needle times, was completed in 2000. The median door to needle time was beyond the recommended National Institute for Neurological Disorders and Stroke (NINDS) standard of 60 minutes. In November 2001, an Acute Stroke Triage Pathway was introduced in the emergency room (ER) to address this issue. The goal of this pathway was to rapidly identify patients eligible for treatment for IV t-PA, so that CT scans and lab studies could be arranged immediately upon ER arrival. Our hypothesis was that the Triage Pathway would shorten door to CT and door to needle times. DESIGN/METHODS: Using retrospective data, pre (n=87) and post (n=47) triage pathway times were compared. The door to CT time was reduced by 11 minutes (p=0.015) and door to needle time was reduced by 18 minutes (p=0.0036) in a subgroup of patients that presented directly to our hospital. CONCLUSIONS: These results indicate that the Acute Stroke Triage Pathway is effective in reducing Door to CT and Door to Needle Times in patients presenting directly to our ER. However, a majority of treatment times were still beyond NINDS recommendations. Stroke Centers require periodic review of their efficiency to ensure that target times are being obtained and may benefit from the use of an Acute Stroke Triage Pathway.

Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice.

A critical element in improving the potency of cancer vaccines, especially pure protein or peptide antigens, is to develop procedures that can strongly but safely increase their ability to induce immune responses. Here, we describe that encapsulation of a pure protein antigen and interleukin-2 (IL-2) together into liposomes significantly improves immune responses and tumor protection. Groups of C57Bl/6 mice were immunized weekly x4 with -0.1 mg of ovalbumin (OVA) injected subcutaneously in PBS or encapsulated in liposomes with or without human recombinant IL-2. Control groups included mice immunized to irradiated E.G7-OVA cells (that express ovalbumin), or to PBS. Sera were collected and pooled by immunization group at baseline and at weeks 2 and 4 to measure antibody responses to OVA by ELISA. Splenocytes obtained at week 4 were tested for anti-OVA cellular responses by ELISPOT. Mice were then challenged to a lethal dose of E.G7-OVA cells to measure tumor-protective immunity. IL-2 liposomes caused no detectable toxicity. Antibody, CD8(+) T cell, and tumor-protective immune responses were markedly enhanced in mice immunized to OVA + IL-2 in liposomes compared to mice immunized to OVA, either alone or encapsulated into liposomes without IL-2. These results indicate that IL-2 liposomes enhance antibody, cellular, and tumor-protective immune responses to immunization with a soluble protein. This may provide a simple, safe, and effective way to enhance the immunogenicity of vaccines that consist of pure protein antigens.

Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine.

A major challenge in the development of more effective vaccines for cancer and other diseases is the development of potent adjuvants that can strongly, simply and safely enhance vaccine immunogenicity. Adjuvants that preferentially enhance Th1 type of responses are particularly desirable, as these responses are believed to play the major role in immune resistance to cancer. This study describes the ability of topical application of imiquimod to act as a potent, safe and simple vaccine adjuvant in mice. Groups of C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1mg/dose) weekly x 4. Imiquimod in a 5% cream formulation was rubbed into the skin over the injection site for 15s to give a dose of approximately 1mg/treatment following each immunization. Control mice were immunized with OVA alone, with irradiated E.G7-OVA cells (that express ovalbumin), with OVA encapsulated in liposomes, or to PBS. Topical imiquimod enhanced anti-OVA antibody responses 100-fold and markedly increased cellular responses compared to mice not given imiquimod. The responses were shifted towards a Th1 phenotype, with marked enhancement of IgG2a, IgG2b, and CD8+ T cell responses and concomitant suppression of IgM and IgG1 responses. More frequent topical applications of imiquimod further enhanced both antibody and cellular responses. There was no detectable local or systemic toxicity associated with treatment. These results indicate that topical imiquimod can safely and strongly enhance both antibody and CD8+ T cell response to OVA immunization, and suggest that it may provide a simple, safe and effective way to enhance the immunogenicity of vaccines in general.

Photoinduced one-electron reduction of alkyl halides by dirhodium(II,II) tetraformamidinates and a related complex with visible light.

Various substituted dirhodium tetraformamidinate complexes, Rh(2)(R-form)(4) (R = p-CF(3), p-Cl, p-OCH(3), m-OCH(3); form = N,N'-diphenylformamidinate), and the new complex Rh(2)(tpgu)(4) (tpgu = 1,2,3-triphenylguanidinate) have been investigated as potential agents for the photoremediation of saturated halogenated aliphatic compounds, RX (R = alkyl group). The synthesis and characterization of the complexes is reported, and the crystal structure of Rh(2)(tpgu)(4) is presented. The lowest energy transition of the complexes is observed at approximately 870 nm and the complexes react with alkyl chlorides and alkyl bromides under low energy irradiation (lambda(irr) > or = 795 nm), but not when kept in the dark. The metal-containing product of the photochemical reaction with RX (X = Cl, Br) is the corresponding mixed-valent Rh(2)(II,III)X (X = Cl, Br) complex, and the crystal structure of Rh(2)(p-OCH(3)-form)(4)Cl generated photochemically from the reaction of the corresponding Rh(2)(II,II) complex in CHCl(3) is presented. In addition, the product resulting from the dimerization of the alkyl fragment, R(2), is also formed during the reaction of each dirhodium complex with RX. A comparison of the dependence of the relative reaction rates on the reduction potentials of the alkyl halides and their C-X bond dissociation energies are consistent with an outer-sphere mechanism. In addition, the relative reaction rates of the metal complexes with CCl(4) decrease with the oxidation potential of the dirhodium compounds. The mechanism of the observed reactivity is discussed and compared to related systems.

Heterogeneous antibody response to polyvalent melanoma vaccines in syngeneic mice.

In this study, a human melanoma vaccine induced antibody responses in mice that varied significantly from animal to animal. BALB/c mice were immunized to a xenogenic human polyvalent melanoma vaccine that has been used in phase II clinical trials in over 600 patients. Mice were bled biweekly for up to 6 weeks to measure antibody responses. IgG antibody responses to the melanoma vaccine components were detectable within 2 weeks but were much stronger at 4 and 6 weeks. When the pooled sera were further analyzed by Western blot, a complex pattern of antigens was detected. When individual sera from identically immunized mice were assayed by Western blot, a consistent, reproducible pattern of antigen recognition was not seen. Rather, we found significantly different antibody responses among the mice. Both the intensity of antibody responses and the pattern of antigens recognized varied from animal to animal. Although there appeared to be immunodominant antigens that produced antibody responses in most mice, no single antigen induced antibody responses in all mice. These results demonstrate that polyvalent vaccines induce heterogeneous antibody responses in mice treated identically. Analysis of the response of selected melanoma patients immunized to the same vaccine revealed similar antibody responses to the antigens in the melanoma vaccine. Heterogeneity may hamper interpretation of vaccine immunogenicity and relevant tumor antigens in humans.

Unidirectional current in a polyacetylene hetero-ionic junction.

Unidirectional electronic current is reported for a device based on the interface between an anionically functionalized and a cationically functionalized polyacetylene. The unidirectional current in this mixed ionically/electronically conducting system is electronic but is regulated by asymmetry in the ionic processes.

The patient with transient cerebral ischemia: a golden opportunity for stroke prevention.

Transient ischemic attack (TIA) provides a golden opportunity for stroke prevention. TIA should be treated as a medical emergency with prompt investigations to determine the mechanism of ischemia and subsequent preventive therapy. The risk of stroke after TIA is estimated to be 10%-20% in the first 90 days. The risk is time-dependent with 50% of the risk accruing in the first 48 hours. In this review, we describe the diagnosis and management of TIA, introduce new concepts in TIA and suggest that all patients with significant TIA should undergo rapid investigation and management to prevent stroke.

Who doesn't receive carotid endarterectomy when appropriate?

OBJECTIVE: The purpose of this study was to identify clinical and nonclinical factors associated with failure to perform carotid endarterectomy (CEA) in patients with clinically appropriate indications. We analyzed data from a prospective cohort study performed at five Veterans Affairs medical centers. Patients were referred for carotid artery evaluation if they had at least 50% stenosis in one carotid artery, had no history of CEA, and were independently classified preoperatively as appropriate candidates for CEA, according to clinical criteria. The primary outcome was receipt of CEA within 6 months of evaluation. Data were collected by medical record review and interview regarding clinical status, and patient and physician perception of the risks and benefits of CEA. RESULTS: Among clinically appropriate candidates for CEA, 66.8% (n = 233) did not undergo the operation. Compared with patients who did undergo CEA, a greater proportion of these patients had no symptoms (68.7% vs 45.7%; P <.001). A twofold greater proportion of patients who did not undergo CEA were in the highest quartile of reported aversion to surgery. Moreover, a fourfold greater proportion were perceived by their physicians to be at less than 5% risk for future stroke without the operation, and more than a twofold greater proportion were believed to experience less than 5% efficacy from the operation by their providers (P <.01). In multivariable analyses, four characteristics were significantly associated with whether an appropriate candidate did not receive CEA: asymptomatic disease, less than 70% stenosis, high expressed aversion to surgery score, and low (<5%) provider-perceived efficacy of the operation. CONCLUSION: Among patients in the Veterans Affairs health care system who are clinically appropriate candidates for CEA, those who did not receive the operation were less likely to have symptomatic disease or high-grade carotid artery stenosis, but were more likely to report high aversion to surgery and to have a provider who believed CEA would not be efficacious.