Vide Infra Research Articles

A Practical and Stereoselective Synthesis of Cinnamyl Alcohols Bearing α‐Cyano or α‐Ester Functional Group from Baylis—Hillman Adducts.

Cinnamyl alcohols bearing ester, acid, or nitrile functional group at the 2-position are very useful synthons for the synthesis of various biologically important compounds. Synthesis of cinnamyl alcohol derivatives from the BaylisHillman adducts has been reported by us and other groups. The conversion can be carried out directly by using 20% aqueous sulfuric acid (for the Baylis-Hillman adducts derived from acrylonitrile) or trifluoroacetic acid (for the Baylis-Hillman adducts derived from acrylates). Recently, Basavaiah and coworkers have reported the two-step, onepot conversion method: TMSOTf-assisted conversion of Baylis-Hillman alcohol into the corresponding primary acetate with acetic anhydride and the following partial hydrolysis with K2CO3 in methanol. In the above chemical transformation, the conversion of secondary acetate into the primary one is the key step. Rearrangement of secondary acetate into the primary one was conducted by following reaction conditions such as DABCO/THF/reflux, montmorillonite K10 clay/microwave, and TMSOTf (cat.)/CH2Cl2. Direct conversion of BaylisHillman alcohol into the corresponding primary acetate can be carried out by the Basavaiahs method: acetic anhydride in the presence of TMSOTf. However, TMSOTf is a moisturesensitive and somewhat expensive reagent. During the preparation of Baylis-Hillman acetate, we found that the use of acetic anhydride in the presence of a catalytic amount of sulfuric acid in CH2Cl2 afforded directly the corresponding primary acetate in excellent yield. In these regards we envisioned that we could develop the more convenient and practical method to convert the BaylisHillman alcohol into the primary acetate or eventually to primary alcohol (Scheme 1 and Table 1). The reaction of Baylis-Hillman adducts with acetic anhydride (1.5 equiv.) in the presence of sulfuric acid (10 mol%) gave the corresponding rearranged cinnamyl acetates quantitatively in dichloromethane at room temperature within 30 min (Actually, the cinnamyl acetate derivatives could be isolated in 92-95% yields.). In order to obtain the corresponding cinnamyl alcohols in a one-pot we tried some reaction conditions for the next partial hydrolysis. Addition of water to the reaction mixture (two-phase system) afforded the hydrolyzed cinnamyl alcohols in trace amounts. The use of THF instead of CH2Cl2 showed better results in the hydrolysis step. However, neither the acetylation in THF nor the subsequent acidic hydrolysis in aq. THF was efficient. As a next choice, we used methanol as solvent after the formation of rearranged acetate in CH2Cl2 and added K2CO3. However, this process showed incomplete reaction and produced some side products. Thus, we finally adapted the two-step procedure involving the well-known hydrolysis protocol, K2CO3 in methanol, after simple workup process of the primary acetates (vide infra). The representative examples are shown in Table 1. As shown in Table 1, the method can be applicable to both of the Baylis-Hillman adducts derived from acrylates or acrylonitrile. The yields are higher than the reported in all cases. The formation of the cinnamyl alcohols is highly stereoselective (E for the ester and acetyl derivatives and Z for the nitrile analogs) as reported. The method has some advantages over the previous methods: (1) higher yields in

Facile Synthesis of Cyclic Vinamidinium p‐Toluenesulfonates.

Recently we have reported on the α-iodination reaction of some cyclic enaminones. The required cyclic enaminones have been synthesized by the reaction of cyclohexane-1,3dione and amines such as aniline in the presence of ptoluenesulfonic acid as the catalyst. During the reaction small amounts of cyclic vinamidinium salt was isolated. From the reaction mixture we could not find and isolate any salt-free vinamidine itself. Elimination of p-toluenesulfonic acid from the salt could be carried out by treatment with triethylamine to afford the cyclic vinamidine (vide infra). The synthesis of vinamidine in a direct method in high yield could not be achieved with excess use of aniline (up to 5 equiv.). The failure might be arised from the basic nature of vinamidine, which trap the acid catalyst and presented as its salt, namely vinamidinium salt. Electronic interactions between p-donor atoms (saturated nitrogen atom in this case) and π-acceptor groups (imino group in this case) through an intervening carbon-carbon double bond make vinamidine as a strong base. Vinamidinium salts have been used as versatile threecarbon building blocks in the synthesis of benzenoid, nonbenzenoid, and hetereocyclic aromatic rings. Certain vinamidinium salts can be used as a UV absorber. Thus, we intended to develop a facile preparation method of cyclic vinamidinium salt and wish to report herein the results. As mentioned above the synthesis of vinamidine in a direct method in high yield could not be carried out with excess use of aniline. We envisioned that the problem could be solved by the use of excess amounts of acid catalyst. The acid catalyst might improve the electrophilicity of the carbonyl carbon of enaminone intermediate 3 and also act as a template for the approach of aniline toward the protonated enaminone (Scheme 1). Thus, we examined the reaction of cyclohexane-1,3-dione (1a) and aniline (2a, 2.0 equiv.) in the presence of p-TsOH (1.0 equiv.). As expected the corresponding vinamidinium salt 4a was isolated in high yield (94%, entry 2). The same experiment with 0.1 equiv. of p-TsOH gave trace amounts of 4a (6%) together with the enaminone 3a (66%) as the major product. As shown in Table 1, the reaction of 1a and 4chloroaniline (2b) or 4-methoxyaniline (2c) showed similar pattern of reaction (entries 2 and 3). The use of dimedone (1b) showed same tendency as those of the cyclohexane-1,3dione cases (entries 5 and 6). It is interesting to note that the use of picric acid instead of p-TsOH also produced the corresponding vinamidinium salt 4d in moderate yield (entry 4). As mentioned before synthesis of salt free vinamidine itself (5a and 5b) could be carried out by the use of Et3N or

A Practical and Stereoselective Synthesis of Cinnamyl Alcohols Bearing α-Cyano or α-Ester Functional Group from Baylis-Hillman Adducts

Cinnamyl alcohols bearing ester, acid, or nitrile functional group at the 2-position are very useful synthons for the synthesis of various biologically important compounds. Synthesis of cinnamyl alcohol derivatives from the BaylisHillman adducts has been reported by us and other groups. The conversion can be carried out directly by using 20% aqueous sulfuric acid (for the Baylis-Hillman adducts derived from acrylonitrile) or trifluoroacetic acid (for the Baylis-Hillman adducts derived from acrylates). Recently, Basavaiah and coworkers have reported the two-step, onepot conversion method: TMSOTf-assisted conversion of Baylis-Hillman alcohol into the corresponding primary acetate with acetic anhydride and the following partial hydrolysis with K2CO3 in methanol. In the above chemical transformation, the conversion of secondary acetate into the primary one is the key step. Rearrangement of secondary acetate into the primary one was conducted by following reaction conditions such as DABCO/THF/reflux, montmorillonite K10 clay/microwave, and TMSOTf (cat.)/CH2Cl2. Direct conversion of BaylisHillman alcohol into the corresponding primary acetate can be carried out by the Basavaiahs method: acetic anhydride in the presence of TMSOTf. However, TMSOTf is a moisturesensitive and somewhat expensive reagent. During the preparation of Baylis-Hillman acetate, we found that the use of acetic anhydride in the presence of a catalytic amount of sulfuric acid in CH2Cl2 afforded directly the corresponding primary acetate in excellent yield. In these regards we envisioned that we could develop the more convenient and practical method to convert the BaylisHillman alcohol into the primary acetate or eventually to primary alcohol (Scheme 1 and Table 1). The reaction of Baylis-Hillman adducts with acetic anhydride (1.5 equiv.) in the presence of sulfuric acid (10 mol%) gave the corresponding rearranged cinnamyl acetates quantitatively in dichloromethane at room temperature within 30 min (Actually, the cinnamyl acetate derivatives could be isolated in 92-95% yields.). In order to obtain the corresponding cinnamyl alcohols in a one-pot we tried some reaction conditions for the next partial hydrolysis. Addition of water to the reaction mixture (two-phase system) afforded the hydrolyzed cinnamyl alcohols in trace amounts. The use of THF instead of CH2Cl2 showed better results in the hydrolysis step. However, neither the acetylation in THF nor the subsequent acidic hydrolysis in aq. THF was efficient. As a next choice, we used methanol as solvent after the formation of rearranged acetate in CH2Cl2 and added K2CO3. However, this process showed incomplete reaction and produced some side products. Thus, we finally adapted the two-step procedure involving the well-known hydrolysis protocol, K2CO3 in methanol, after simple workup process of the primary acetates (vide infra). The representative examples are shown in Table 1. As shown in Table 1, the method can be applicable to both of the Baylis-Hillman adducts derived from acrylates or acrylonitrile. The yields are higher than the reported in all cases. The formation of the cinnamyl alcohols is highly stereoselective (E for the ester and acetyl derivatives and Z for the nitrile analogs) as reported. The method has some advantages over the previous methods: (1) higher yields in

Facile Synthesis of Cyclic Vinamidinium p-Toluenesulfonates

Recently we have reported on the α-iodination reaction of some cyclic enaminones. The required cyclic enaminones have been synthesized by the reaction of cyclohexane-1,3dione and amines such as aniline in the presence of ptoluenesulfonic acid as the catalyst. During the reaction small amounts of cyclic vinamidinium salt was isolated. From the reaction mixture we could not find and isolate any salt-free vinamidine itself. Elimination of p-toluenesulfonic acid from the salt could be carried out by treatment with triethylamine to afford the cyclic vinamidine (vide infra). The synthesis of vinamidine in a direct method in high yield could not be achieved with excess use of aniline (up to 5 equiv.). The failure might be arised from the basic nature of vinamidine, which trap the acid catalyst and presented as its salt, namely vinamidinium salt. Electronic interactions between p-donor atoms (saturated nitrogen atom in this case) and π-acceptor groups (imino group in this case) through an intervening carbon-carbon double bond make vinamidine as a strong base. Vinamidinium salts have been used as versatile threecarbon building blocks in the synthesis of benzenoid, nonbenzenoid, and hetereocyclic aromatic rings. Certain vinamidinium salts can be used as a UV absorber. Thus, we intended to develop a facile preparation method of cyclic vinamidinium salt and wish to report herein the results. As mentioned above the synthesis of vinamidine in a direct method in high yield could not be carried out with excess use of aniline. We envisioned that the problem could be solved by the use of excess amounts of acid catalyst. The acid catalyst might improve the electrophilicity of the carbonyl carbon of enaminone intermediate 3 and also act as a template for the approach of aniline toward the protonated enaminone (Scheme 1). Thus, we examined the reaction of cyclohexane-1,3-dione (1a) and aniline (2a, 2.0 equiv.) in the presence of p-TsOH (1.0 equiv.). As expected the corresponding vinamidinium salt 4a was isolated in high yield (94%, entry 2). The same experiment with 0.1 equiv. of p-TsOH gave trace amounts of 4a (6%) together with the enaminone 3a (66%) as the major product. As shown in Table 1, the reaction of 1a and 4chloroaniline (2b) or 4-methoxyaniline (2c) showed similar pattern of reaction (entries 2 and 3). The use of dimedone (1b) showed same tendency as those of the cyclohexane-1,3dione cases (entries 5 and 6). It is interesting to note that the use of picric acid instead of p-TsOH also produced the corresponding vinamidinium salt 4d in moderate yield (entry 4). As mentioned before synthesis of salt free vinamidine itself (5a and 5b) could be carried out by the use of Et3N or

Highly Stable Polymers based on Poly(m -carboranyl-siloxane) Elastomers

ABSTRACTPoly(m-carboranyl-siloxane) elastomers containing a mixture of di-methyl- and methyl(phenyl)-silyl units were synthesised using the Ferric Chloride catalysed condensation reaction between di-chloro-di-organosilane and 1, 7-bis(di-methyl(methoxy)silyl)-m-carborane. These prepared polymers were aged either by heating in air at elevated temperature or by λ-irradiation from a 60Co source. Multinuclear (1H, 13C and 11B) solid and solution state nuclear magnetic resonance was used to evaluate degradation. λ-irradiation doses to 1 MGy were found to induce only a small reduction in elastomer properties as evidenced by a reduction in segmental chain dynamics. Ageing at temperatures below 350°C similarly displayed a small reduction in segmental chain dynamics together and a concomitant weight loss as measured by differential scanning calorimetry. Above 350°C degradation of the elastomer was dramatic with a decreased segmental chain dynamics and oxidation of the carborane cage, vide infra.

Book of the Month: On the Fabric of the Human Body, Books III and IV

Book of the Month: On the Fabric of the Human Body, Books III and IV

On the Fabric of the Human Body, Books III and IV

On the Fabric of the Human Body, Books III and IV

The first experimental test of the hypothesis that enzymes have evolved to enhance hydrogen tunneling.

The literature hypothesis that "the optimization of enzyme catalysis may entail the evolutionary implementation of chemical strategies that increase the probability of quantum-mechanical tunneling" is experimentally tested herein for the first time. The system employed is the key to being able to provide this first experimental test of the "enhanced hydrogen tunneling" hypothesis, one that requires a comparison of the three criteria diagnostic of tunneling (vide infra) for the same, or nearly the same, reaction with and without the enzyme. Specifically, studied herein are the adenosylcobalamin (AdoCbl, also known as coenzyme B(12))-dependent diol dehydratase model reactions of (i). H(D)(*) atom abstraction from ethylene glycol-d(0) and ethylene glycol-d(4) solvent by 5'-deoxyadenosyl radical (Ado(*)) and (ii.) the same H(*) abstraction reactions by the 8-methoxy-5'-deoxyadenosyl radical (8-MeOAdo(*)). The Ado(*) and 8-MeOAdo(*) radicals are generated by Co-C thermolysis of their respective precursors, AdoCbl and 8-MeOAdoCbl. Deuterium kinetic isotope effects (KIEs) of the H(*)(D(*)) abstraction reactions from ethylene glycol have been measured over a temperature range of 80-120 degrees C: KIE = 12.4 +/- 1.1 at 80 degrees C for Ado(*) and KIE = 12.5 +/- 0.9 at 80 degrees C for 8-MeOAdo(*) (values ca. 2-fold that of the predicted maximum primary times secondary ground-state zero-point energy (GS-ZPE) KIE of 6.4 at 80 degrees C). From the temperature dependence of the KIEs, zero-point activation energy differences ([E(D) - E(H)]) of 3.0 +/- 0.3 kcal mol(-)(1) for Ado(*) and 2.1 +/- 0.6 kcal mol(-)(1) for 8-MeOAdo(*) have been obtained, both of which are significantly larger than the nontunneling, zero-point energy only maximum of 1.2 kcal mol(-)(1). Pre-exponential factor ratios (A(H)/A(D)) of 0.16 +/- 0.07 for Ado(*) and 0.5 +/- 0.4 for 8-MeOAdo(*) are observed, both of which are significantly less than the 0.7 minimum for nontunneling behavior. The data provide strong evidence for the expected quantum mechanical tunneling in the Ado(*) and 8-MeOAdo(*)-mediated H(*) abstraction reactions from ethylene glycol. More importantly, a comparison of these enzyme-free tunneling data to the same KIE, (E(D) - E(H)) and A(H)/A(D) data for a closely related, Ado(*)-mediated H(*) abstraction reaction from a primary CH(3)- group in AdoCbl-dependent methylmalonyl-CoA mutase shows the enzymic and enzyme-free data sets are identical within experimental error. The Occam's Razor conclusion is that at least this adenosylcobalamin-dependent enzyme has not evolved to enhance quantum mechanical tunneling, at least within the present error bars. Instead, this B(12)-dependent enzyme simply exploits the identical level of quantum mechanical tunneling that is available in the enzyme-free, solution-based H(*) abstraction reaction. The results also require a similar, if not identical, barrier width and height within experimental error for the H(*) abstraction both within, and outside of, the enzyme.

New insights into the chemistry of oxomolybdenum(VI) complexes with N-salicylidene-2-aminoethanol

Oxomolybdenum(VI) complexes with tridentate Schiff base, N-salicylidene-2-aminoethanol (H 2sae), has been synthesised by the reaction of Mo(O) 2(sal) 2 (where Hsal=salicylic aldehyde) with 2-aminoethanol. This reaction leads to dimeric [MoO(μ-O)(sae)] 2 and new monomeric [Mo(O) 2(sae){1,2-O (−)C 6H 4C(H)N (+)(H)C 2H 4OH}] ( 1) compounds. Also substitution of acetylacetonate ligand in Mo(O) 2(acac) 2 by H 2sae in EtOH leads to the same complexes (vide infra), but in MeOH monomeric compound Mo(O) 2(sae)(MeOH) ( 2) was formed. The molecular structure of complexes 1 and 2 have been determined by X-ray studies, which confirm that one of the H 2sae co-ordinates as η 3-tridentate O,N,O′ ligand, while in complex 1 this ligand exists also in zwitterionic form with intramolecular hydrogen bonding, O⋯HN, 2.584(3) Å, of phenolic oxygen bonded to the molybdenum atom. The crystals of 1 are triclinic, space group P 1 ̄ , a=8.483(2) Å, b=10.187(3) Å, c=11.034(3) Å, α=105.26(2)°, β=95.29(2)°, γ=95.10(2)°, and D calcd=1.666(1) g cm −3 for Z=2. The crystals of 2 are monoclinic, space group P2 1/ c, a=6.697(2) Å, b=7.375(2) Å, c=24.100(3) Å, β=92.76(5)°, and D calcd=1.805(1) g cm −3 for Z=4.

Novel Protein Kinase Inhibitors: SMART Drug Design Technology

In retrospect, the emergence of protein kinase drug discovery dates to the identification of the first oncogenic protein kinase, Src, about 25 years ago. This work has led to worldwide research efforts to investigate the genomic and proteomic relationships of protein kinases in disease, cellular mechanisms involving protein kinases in signal transduction, structural biology and modes of both activation and inhibition of protein kinases, and drug discovery focused on novel protein kinase inhibitors (1–20). It is now known that protein kinases constitute a superfamily of therapeutic targets that include >500 members relative to recent sequencing of the human genome (21–23). Key classes of protein kinases (Table 1) include receptor tyrosine kinases (e.g., epidermal growth factor receptor [EGFR], platelet-derived growth factor receptor [PDGFR], and vascular endothelial growth factor receptor [VEGFR]), nonreceptor tyrosine kinases (e.g., Src and Abl), receptor serine/threonine kinases (e.g., transforming growth factor receptor [TGFR]), and nonreceptor serine/threonine and dual specificity kinases (e.g., cyclin-dependent kinase [CDK], m-Tor, and MEK). The tyrosine kinases comprise about 20% of known or predicted protein kinases. As highlighted in Figures 1 and 2, key milestones and advances in protein kinase inhibitor drug discovery include focused studies on protein kinase C (PKC), CDK, MEK, p38 mitogen-activated protein kinase (MAPK), Abl kinase, Src kinase, insulin receptor kinase (IRK), and EGFR kinase. Such work has embraced an increased understanding of the roles of protein kinases in signal transduction pathways, including aberrant cellular mechanisms underlying cancer (e.g., PKC, CDK, Abl kinase, Src kinase, and several growth factor receptor kinases). Structural studies have contributed significantly to recent drug discovery campaigns (e.g., nonreceptor kinases, such as Src, Lck, and Abl kinase, and several growth factor receptor kinases). Although the major mode of inhibition of protein kinases has been focused on the ATP binding site, there have been recent achievements made to exploit both allosteric and substrate binding site interactions to advance novel molecules (vide infra). Importantly, very recent Food and Drug Administration (FDA) approvals of both Gleevec (STI-571; Novartis AG International, Basel, Switzerland) (24–26) and Iressa® (ZD1839; AstraZeneca, Wilmington, De, USA) (27–29) exemplify success in drug development of tyrosine kinase inhibitors with particular therapeutic indications for certain cancers.

Heparin-induced thrombocytopenia: pathogenesis and management.

Heparin-induced thrombocytopenia: pathogenesis and management.

Synthesis of 2-Benzylphenols: Transformation of the Baylis-Hillman Adducts Derived from 2-Cyclohexen-1-one

an extension of the reaction, we intended to prepare acridine skeleton from the Baylis-Hillman adducts of 2-cyclohexen1-one as shown in Scheme 1. However, we could not prepare the desired compounds via the reaction scheme (vide infra). Instead, we could obtain 2-benzylphenol derivatives in good yields as shown in Scheme 2 and wish to report herein the results. The Friedel-Crafts alkylation reaction is one of the most powerful methods to form the carbon-carbon bond in organic reactions. The Friedel-Crafts benzylation reaction is of great synthetic significance in industrial processes. 3 However, synthesis of 2-benzylphenols regioselectively from phenols or benzyl phenyl ethers is difficult due to the formation of ortho-/para- mixtures. 4 Synthesis of these compounds by Fries rearrangement of phenyl phenylacylates also suffers from the formation of mixtures. 5 Ortho-specific alkylation of phenols via 1,3,2-benzodioxaborins was known. 6 1,3,2-Benzodioxaborins can be reduced to orthoalkyl phenols with tert-butylamine borane in the presence of aluminum chloride. The Baylis-Hillman reaction of 2-fluorobenzaldehyde (1a) and 2-cyclohexen-1-one (2) was carried out in aqueous THF with the aid of DMAP at room temperature to give the corresponding adduct 3a in 58% yield as reported previously. 7 Acetylation of 3a with Ac2O/DMAP gave 4a in 91% yield. Initially, we examined the reaction of 4a and ptoluenesulfonamide in the presence of K 2CO3 in DMF. However, 2-(2-fluorophenyl)methylphenol (5a) was isolated in 74% yield, unexpectedly. The formation of 5a occurred well without tosylamide. Actually, the yield of 5a was improved up to 94% without tosylamide as shown in Table 1 (entry 1). Thus, we prepared some Baylis-Hillman acetates of 2cyclohexen-1-one and examined their conversion to 2arylmethylphenols and the results are summarized in Table 1. As mentioned previously, the Baylis-Hillman reaction of 1 and 2 was carried out in aqueous THF in the presence of 0.1 equiv. of DMAP. 7 The corresponding adducts 3a-h were obtained in reasonable yields (41-64%) at room temperature. Following conversion to their acetate 4a-h was excellent in all cases (CH2Cl2, Ac2O/DMAP, rt, 90-98%). The reaction of 4a-f in DMF in the presence of K 2CO3 (1.0 equiv) gave 5a-f in good yields (89-96%) in short time (1-2 h) at 60-70 o C. 8 The formation of 5g, the quinoline derivative, was carried out at room temperature. The reaction is believed to occur as depicted in Scheme 2: potassium carbonate assisted elimination of acetic acid and the following keto-enol tautomerization and 1,5-hydrogen transfer. 9 We could not obtain the corresponding phenol derivative from the analogous reaction with 4h, derived from hexanal. Intractable mixtures were observed on tlc at 60-70 o C. Instead, we could isolate cyclohexenone derivative 6 in 40% yield at room temperature. 10 The structure of 6 was determined by 1 H, 13 C, and 1 H- 1 H COSY. 8 In conclusion we disclosed unusual transformation of the Baylis-Hillman acetates of 2-cyclohexen-1-one into 2arylmethylphenols. Further chemical transformation of the products to xanthene derivatives via the nucleophilic aromatic substitution strategy and the synthesis of acridines are underway.

Total synthesis of phorboxazole A.

Total synthesis of phorboxazole A.

Stopping cross sections forN4+→Hat low projectile velocity

We study the time-dependent dynamics of N 4 + ions colliding with atomic hydrogen for projectile energies ranging from a fraction of an eV/amu up to 25 keV/amu using the electron-nuclear dynamics (END) formalism. The END theory obtains the electron-nuclear coupled equations of motion from the time-dependent variational principle employing a coherent state parametrization of the wave function. This approach leads to a simultaneous nonadiabatic dynamics of all the electrons and nuclei. We calculate and discuss dynamical trajectories, deflection functions, final charge states, differential cross sections, and energy loss. Quantum effects of the forward peak scattering are emphasized. Due to the strong interaction between the heavy and the hydrogen atom, a diffuse ion (vide infra) is formed, leading to acceleration or energy gain of the projectile. For the case of the electron transfer cross section, we found that it does not follow the Langevin-type cross section at low projectile energies as reported by other methods. Present results show good agreement with available experimental data.

Horizontal canal paroxysmal positional vertigo (HCPPV) vs classical BPPV (new concepts about mechanism and domiciliary repositioning of particles).

Some new modificutiont of existing diagnostic and therapeutic manoeuvres (repositioning of particles) have been proposed, basing an the applications of the principles of hydrodynamics, inertial and gravitational forces in the semicircular canals. The above has been tried successfully on patients with benign paroxysmal positional vertigo (BPPV) and horizontal eanal paroxysmal positional vertigo (HCPPV) which can be executed by the patients themselves at home without the kelp of a therapist.Benign paroxysmal positional vertigo (BPPV) is a well-established entity whereas Horizontal Canal Paroxysmal Positional Vertigo (HCPPV) is a recently proposed one. In positional vertigo any canal may be involved. It is quite possible that in the past this diagnosis (HCPPV) was missed in many of the cases of positional vertigo. Kapfschuttel nystagmus (head-shaking nystanmas) is induced by side to side (to and fro) movements of the head around a vertical axis in the plane of the horizontal semicircular canal which is thought to be sensitise the labyrinth, Any manoeuvres that in induce nystagmus with or without vertino is hound to he a manifestation of an organic lesion and not a non-organic one. In a number of instances the postionul test Jor BPPV may yield negative results; but doing this test after kopfschuttel test a dormant positional nystagmus may appear on the surface i.e. uncovered in a number of cases which may have remained undetected if Kopfschutlel manoeuvre were not done. This implies- that by Kopfsi huttel test both the horizontal and vertical canals are sensitised.Moreover, Kopfschuttel nystaagmus is likely to be a manifestation of the horizontal canal stimulation, at leastin some cases, since the movements are executed in the plane of the horizontal canal (vide infra) when displaced otoconia impinges on the cupula /. crista bringing about its stimulation leading to vertigo and or nystagmus.

Endophthalmitis following cataract surgery in Sweden. The 1998 national prospective survey.

To investigate the morbidity of postoperative endophthalmitis (POE) following cataract surgery in Sweden in 1998. Clinically presumed cases of POE were reported in a prospective survey in which all Swedish ophthalmic surgical units except one had agreed to participate. Data on intraocular cultures and visual outcomes at 3 months after infection were supplied. Surgical cases that became infected were identified in the Swedish National Cataract Register, thereby enabling screening for various putative risk factors. The nationwide incidence of POE amounted to 58 cases out of 54 666 cataract operations, or 0.1% of surgical cases. The predominant aetiology was gram-positive bacteria, which comprised 57% of the material. Acrylic intraocular lenses were found to decrease the risk of POE significantly in comparison to hydrogel and polymethylmethacrylate lenses. The incidence of POE after cataract surgery in Sweden is similar to that currently reported elsewhere in the developed world. We hope that continued registration of cases of POE in Sweden will shed light on the possible influences of various prophylactic measures and different intraocular lens materials on the development of postoperative infection.

Antioxidative activity of 3-aryl-benzofuran-2-one stabilizers (Irganox®HP-136) in polypropylene

Irganox®HP-136(lactone), which is a mixture of 90% of 5,7-di- tert-butyl-3-(3,4-dimethylphenyl)3 H-benzofuran-2-one and 10% of 5,7-di- tert-butyl-3-(2,3-dimethylphenyl)3 H-benzofuran-2-one behaves as a medium strength chain-breaking antioxidant during polypropylene oxidation at 180 and 200 °C. The critical concentration (vide infra) required to inhibit oxidation is higher than that of the phenolic antioxidant 2246. The lactone is slowly consumed during the induction period and then much faster when the critical concentration is reached. Phosphites, sulphides and phenols increase the efficiency of the lactone during polymer oxidation. The use of lactone allows the amount of phenolic and phosphorous containing stabilizers to decrease without decreasing the thermooxidative stability of the polymer.

Controlling the Energy and Electron Transfer in a Novel Ruthenium Bipyridyl Complex: An ESR Study

A novel ruthenium complex has been synthesized. It is composed of three bipyridyl ligands, one of which is modified and has two hydroxamate groups. Photoexcitation of the complex with blue light (λmax = 477 nm) leads to the formation of a long-lived nitroxyl radical on hydroxamate as was detected and characterized by ESR. In anaerobic conditions, the radical was not formed, suggesting that a reactive oxygen species is required for generating the nitroxyl radical. The quenching of the excited state of ruthenium bipyridyl complexes by molecular oxygen can generate either singlet oxygen via energy transfer or superoxide radical via electron transfer. In this latter case the superoxide radical is confined in a cage complex (vide infra). Singlet oxygen, generated via energy transfer from Ru(II) in its excited state, is the reactive species that is responsible for the oxidation of the hydroxamate group to its corresponding nitroxyl radical. This was confirmed by using a specific quencher (sodium azide) and by following the kinetics of the nitroxyl radical formation in deuterated solvents. Moreover, we can turn on the electron-transfer pathway by liberating superoxide radicals and producing a strong oxidant, Ru(III), from the collision “cage” complex proposed earlier (Zhang, X.; Rodgers, M. A. J. J. Phys. Chem. 1995, 99, 12797−12803.) This was achieved using compounds with either chemical (spin traps) or enzymatic (superoxide dismutase) affinity to superoxide radicals. Thus, the rate and yield of the nitroxyl radical formation in the novel ruthenium complex can be increased by almost thirty times.

The history of folic acid.

The history of folic acid.

Total synthesis of (+)-phorboxazole A.

Total synthesis of (+)-phorboxazole A.