Intramolecular behaviors of anthryldicarbenic systems: dibenzo[b,f]pentalene and 1H,5H-dicyclobuta[de,kl]anthracene.

9,10-Bis[methoxy(trimethylsilyl)methyl]anthracenes (24), synthesized from 9,10-dilithioanthracene (26) and bromomethoxytrimethylsilylmethane (27, 2 equiv), decompose (550-650 degrees C/10(-3) mmHg) carbenically to dibenzo[b,f]pentalene (28, > 48%). 9,10-Anthryldicarbenes 39 or their equivalents convert to pentalene 28 rather than di-peri-cyclobutanthracenes 30 and 31, benzobiphenylene 32, or extended rearrangement products 33-38. Formation of 28 from 24 raises questions with respect to the behavior of 1,3,4,6-cycloheptatetraenyl-1-carbenes 49, 2,4,5,7-cyclooctatetraenylidene 51, 2,5,7-cyclooctatriene-1,4-diylidene 52, 1,2,4,5,7-cyclooctapentaene 53, and bicyclo[4.1.0]heptatrienyl-1-carbenes 54 and to carbon-skeleton and hydrogen rearrangements of anthryldicarbenes 39 and/or their equivalents at various temperatures. 1,5-Bis[methoxy(trimethylsilyl)methyl]anthracenes (25), prepared from 1,5-diiodoanthracene (63) and methoxytrimethylsilylmethylzinc bromide (57, 2 equiv) as catalyzed by PdCl(2)(PPh(3))(2), yield the di-peri-carbenic reaction product 1H,5H-dicyclobuta[de,kl]anthracene (30, > 40%) on pyrolysis at 550-650 degrees C/10(-3) mmHg. Proof of structure and various aspects of the mechanisms of formation of 30 are discussed.

(Z)-5-(2-thienylmethylene)-2,4-imidazolidinedione.

The major product formed in the thermolysis of 5-diazouracil in thiophene at 423-433 K has been identified as the unexpected compound (Z)-5-(2-thienylmethylene)-2,4-imidazolidinedione, C8H6N2O2S, by X-ray analysis. The molecule is a hydantoin derivative with a thienylmethylene group substituted at the 5-position. The structure is disordered in that the thiophene ring exists in two orientations which are related by an approximate 180 degree rotation about the C(6)-C(7) bond. All of the N and O atoms are involved in an intermolecular hydrogen-bonding network via N-H...O interactions. This network consists of an infinite chain along the a-axis direction and a cyclic trimer arrangement which branches from this chain. The molecules are arranged in the unit cell in pleated sheets which are approximately perpendicular to the c axis.

Induction of psoriasiform changes in guinea pig skin by propranolol.

BACKGROUND: The ability of beta-adrenergic blocking agents to induce psoriasis as an adverse effect prompted us to use such an agent to induce psoriasis in guinea pigs. METHODS: Thirty female albino guinea pigs were divided into four groups. Group 1 received propranolol, 0.1 mg/day, dissolved in 2 mL of normal saline, orally by gavage for 30 days. Group 2 was given the same treatment, but in addition intradermal injections of propranolol with Freund's complete adjuvant, injected at weekly intervals. Group 3 (five animals) received 2 mL saline, and group 4 additional injections of adjuvant without propranolol. Groups 3 and 4 served as normal controls. RESULTS: All animals of group 2 (which received propranolol orally and in addition intradermal injections of adjuvant) developed psoriasiform epidermal hyperplasia with acanthosis. Parakeratosis, papillomatosis, and formation of microabscesses, all characteristic signs of psoriasis, have not been seen in any of the skin samples of this group. Skin samples from group 1 animals receiving propranolol orally showed normal epidermis and dermis. They showed exactly the same histologic picture as the control groups 3 and 4. CONCLUSIONS: Beta-blockers given orally for 30 days do not cause any significant skin changes in guinea pigs. When given with a weekly intradermal injection of Freund's complete adjuvant, they cause psoriasiform epidermal hyperplasia. Although the overall histologic appearance of the skin of group 2 resembled psoriasis, it lacked important histologic features characteristic of this disease. It seems, therefore, that the model, per se, does not fulfill the initial expectations as an experimental model for psoriasis; however, this model has potential in the study of adverse drug reactions. Perhaps by introducing modifications to the experimental protocol, we may succeed also in developing a better model for experimental psoriasis.

Transcriptional regulation of class-I major histocompatibility complex genes transformed in murine cells is mediated by positive and negative regulatory elements.

The expression of class-I major histocompatibility complex (MHC) antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low or absent; a phenotype that correlates with the high tumorigenicity of these cell lines. In primary mouse embryonal fibroblasts (MEF) from class-I transgenic mice (PD1 transgenic mice), Ad12-mediated transformation results in down-regulation of both endogenous genes and the transgene. Functional analysis of class-I regulatory elements revealed that the suppression of a class-I promoter is mediated by two negative regulatory elements, one of which functions specifically in Ad12-transformed cells. In addition, Ad12-transformed cells produce only minute amounts of the nuclear factors that bind to the major class-I enhancer, RI (region I or H2TF1). A silencer element derived from the 5' region of the miniature swine class-I gene (PD1) is capable of competing for the binding of nuclear factors to a second enhancer, RII (region II or CREII), that is located upstream from RI in the class-I regulatory element (CRE). Based on these results, we propose that down-regulation of class-I genes in Ad12-transformed cells is mediated mainly by negative regulators.

Structure of (E)-5-(methoxymethylene)-2,4-imidazolidinedione.

C5H6N2O3, Mr = 142.11, monoclinic, P2(1)/n, a = 3.862 (1), b = 16.329 (2), c = 10.088 (1) A, beta = 98.77 (2) degrees, V = 628.7 (2) A3, Z = 4, Dx = 1.50 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.18 cm-1, F(000) = 296, T = 296 K, R = 0.035 for 1124 independent reflections with I greater than 3 sigma(I). The structure is a hydantoin derivative with a methoxymethylene group substituted at the 5-position. Excluding the H atoms, the molecule is planar to within 0.032 A. All of the N and O atoms are involved in an intermolecular hydrogen-bonding network via N--H...O and C--H...O interactions. The packing arrangement is a linear ribbon motif with the ribbons stacked to form the short a axis.

Topical treatment of toxic epidermal necrolysis with Iodoplex.

Toxic epidermal necrolysis (TEN) is characterized by extensive exfoliation of the epidermis, mucosal ulcerations and fever, after a recent intake of a new drug. TEN developed in an 8-year-old girl after she ingested sulfonamides and sustained skin injuries of 90% total body surface area. In addition to her critical care management, local treatment consisted of Iodoplex cream (Biosearch Laboratories, Haifa, Israel), a long-acting antimicrobial agent from which iodine is slowly released over 48 hours. Healing was observed within 8 to 17 days after initial application. Iodoplex cream is an additional topical agent for the local treatment of TEN when porcine heterografts or allografts might not be feasible.