Phenylboronic acids in crystal engineering: Utility of the energetically unfavorable syn,syn-conformation in co-crystal design

Phenylboronic acids can exist, in principle, in three different conformers (syn,syn; syn,anti and anti,anti) with distinct energy profiles. In their native state, these compounds prefer the energetically favored syn, anti-conformation. In molecular complexes, however, the functionality exhibits conformational diversity. In this paper we report a series of co-crystals, with N-donor compounds, prepared by a design strategy involving the synthons based on the syn, syn-conformation of the boronic acid functionality. For this purpose, we employed compounds with the 1,2-diazo fragment (alprazolam, 1H-tetrazole, acetazolamide and benzotriazole), 1,10-phenanthroline and 2,2'-bipyridine for the co-crystallization experiments. However, our study shows that the mere presence of the 1,2-diazo fragment in the coformer does not guarantee the successful formation of co-crystals with a syn, syn-conformation of the boronic acid. [GRAPHICS] The -B(OH)(2) fragment makes unsymmetrical O-H center dot center dot center dot N heterosynthons with alprazolam (ALP) and 1,10-phenanthroline (PHEN). In the co-crystals of phenylboronic acids with 1H-tetrazole (TETR) and 2,2'-bipyridine (BPY), the symmetrical boronic acid dimer is the major synthon. In the BPY complex, boronic acid forms linear chains and the pyridine compound interacts with the lateral OH of boronic acid dimers that acts as a connector, thus forming a ladder structure. In the TETR complex, each heterocycle interacts with three boronic acids. While two boronic acids interact using the phenolic group, the third molecule generates O-H center dot center dot center dot N hydrogen bonds using the extra OH group, of -B(OH)(2) fragment, left after the dimer formation. Thus, although molecules were selected retrosynthetically with the 1,2-diazo fragment or with nearby hetero-atoms to induce co-crystal formation using the syn,syn-orientation of the -B(OH)(2) functionality, co-crystal formation is in fact selective and is probably driven by energy factors. Acetazolamide (ACET) contains self-complementary functional groups and hence creates stable homosynthons. Phenylboronic acids being weak competitors fail to perturb the homosynthons and hence the components crystallize separately. Therefore, besides the availability of possible hydrogen bond acceptors in the required position and orientation, the ability of the phenyl-boronic acid to perturb the existing interactions is also a prerequisite to form co-crystals. This is illustrated in the table below. In the case of ALP, PHEN and BPY, the native structures are stabilized by weak interactions and may be influenced by the boronic acid fragment. Thus phenylboronic acids can attain co-crystals with those compounds, wherein the cyclic O-H center dot center dot center dot N hydrogen bonds are stronger than the individual homo-interactions. This can lower the lattice energy of the molecular complex as compared with the individual crystals. [GRAPHICS] Phenylboronic acids show some selectivity in the formation of co-crystals with N-heterocycles. The differences in solubility of the components fall short to provide a possible reason for the selective formation of co-crystals only with certain compounds. These compounds, being weak acids, do not follow the Delta pK(a) analysis and hence fail to provide any conclusive observation. Theoretical results show that of the three conformers possible, the syn,anti conformer is the most stable. The relative stabilities of the three conformers syn,anti,syn,syn and anti,anti are 0.0, 2.18 and 3.14 kcal/mol, respectively. The theoretical calculations corroborate the fact that only energetically favorable synthons can induce the formation of heterosynthons, as in ALP and PHEN complexes. From a theoretical and structural analysis it is seen that phenylboronic acids will form interactions with those molecules wherein the heterocyclic and acidic fragments can interrupt the homosynthons. However, the energy profile is shallow and can be perturbed easily by the presence of competing functional groups (such as OH and COOH) in the vicinity. [GRAPHICS] .

Intestinal absorption by Sarotherodon galilaeus (syn Tilapia galilaea ) of Lake Kainji, Nigeria

Carbohydrates, protein, lipid and crude fibre were found to reduce in amount from the anterior to posterior regions along the gut of Sarotherodon galilaeus collected from Lake Kainji. Different regions of the gut exhibited different absorptive powers and all the compounds were differently absorbed in amount. Different sizes of fish showed different absorptive capacity

Rifting process and formation mechanisms of syn-rift stage prolongation in the deepwater basin, northern South China Sea

Based on the latest seismic and geological data, tectonic subsidence of three seismic lines in the deepwater area of Pearl River Mouth Basin (PRMB), the northern South China Sea (SCS), is calculated. The result shows that the rifting process of study area is different from the typical passive continental margin basin. Although the seafloor spreading of SCS initiated at 32 Ma, the tectonic subsidence rate does not decrease but increases instead, and then decreases at about 23 Ma, which indicates that the rifting continued after the onset of seafloor spreading until about 23 Ma. The formation thickness exhibits the same phenomenon, that is the syn-rift stage prolonged and the post-rift thermal subsidence delayed. The formation mechanisms are supposed to be three: (1) the lithospheric rigidity of the northern SCS is weak and its ductility is relatively strong, which delayed the strain relaxation resulting from the seafloor spreading; (2) the differential layered independent extension of the lithosphere may be one reason for the delay of post-rift stage; and (3) the southward transition of SCS spreading ridge during 24 to 21 Ma and the corresponding acceleration of seafloor spreading rate then triggered the initiation of large-scale thermal subsidence in the study area at about 23 Ma.

Direct Carbon-Carbon Bond Formation via Reductive Soft Enolization: A Kinetically Controlled syn-Aldol Addition of alpha-Halo Thioesters and Enolizable Aldehydes

The direct addition of enolizable aldehydes and a-halo thioesters to produce beta-hydroxy thioesters enabled by reductive soft enolization is reported. The transformation is operationally simple and efficient and has the unusual feature of giving high syn-selectivity, which is the opposite of that produced for (thio)esters under conventional conditions. Moreover, excellent diastereoselectivity results when a chiral nonracemic alpha-hydroxy aldehyde derivative is used.

syn-Benzene dioxides: chemoenzymatic synthesis from 2,3-cis-dihydrodiol derivatives of monosubstituted benzenes and their application in the synthesis of regioisomeric 1,2- and 3,4-cis-dihydrodiols and 1,4-dioxocins

cis-2,3-Dihydrodiol metabolites of monosubstituted halobenzenes and toluene have been used as synthetic precursors of the corresponding 3,4-cis-dihydrodiols. Enantiopure syn-benzene dioxide intermediates were reduced to the 3,4-cis-dihydrodiols and thermally racemised via the corresponding 1,4-dioxocins. The syn-benzene dioxide-1,4-dioxocin valence tautomeric equilibrium ratio was found to be dependent on the substituent position. The methodology has also been applied to the synthesis of both enantiomers of the 1,2-(ipso)- and 3,4-cis-dihydrodiols of toluene. This chemoenzymatic approach thus makes available, for the first time, all three possible cis-dihydrodiol regioisomers of a monosubstituted benzene.

Pharmacological characterisation of neuropeptide F (NPF)-induced effects on the motility of Mesocestoides corti (syn. Mesocestoides vogae) larvae

Neuropeptide F is the most abundant neuropeptide in parasitic flatworms and is analogous to vertebrate neuropeptide Y. This paper examines the effects of neuropeptide F on tetrathyridia of the cestode Mesocestoides vogae and provides preliminary data on the signalling mechanisms employed. Neuropeptide F ( greater than or equal to 10 muM) had profound excitatory effects on larval motility in vitro. The effects were insensitive to high concentrations (I mM) of the anaesthetic procame hydrochloride suggesting extraneuronal sites of action. Neuropeptide F activity was not significantly blocked by a FMRFamide-related peptide analog (GNFFRdFamide) that was found to inhibit GNFFRFamide-induced excitation indicating the occurrence of distinct neuropeptide F and FMRFamide-related peptide receptors. Larval treatment with guanosine 5'-O-(2-thiodiphosphate) trilithium salt prior to the addition of neuropeptide F completely abolished the excitatory effects indicating the involvement of G-proteins and a G-protein coupled receptor in neuropeptide F activity. Addition of guanosine 5'-O-(2-thiodiphosphate) following neuropeptide F had limited inhibitory effects consistent with the activation of a signalling cascade by the neuropeptide. With respect to Ca2+ involvement in neuropeptide F-induced excitation of M. vogae larvae, the L-type Ca2+-channel blockers verapamil and nifedipine both abolished neuropeptide F activity as did high Mg+ concentrations and drugs which blocked sarcoplasmic reticulum Ca2+-activated Ca2+-channels (ryanodine) and sarcoplasmic reticulum Ca2+ pumps (cyclopiazonic acid). Therefore, both extracellular and intracellular Ca2+ is important for neuropeptide F excitation in M. vogae. With resepct to second messengers, the protein kinase C inhibitor chelerythrine chloride and the adenylate cyclase inhibitor MDL-2330A both abolished neuropeptide F-induced excitation. The involvement of a signalling pathway that involves protein kinase C was further supported by the fact that phorbol-12-myristate-13-acetate,known to directly activate protein kinase C, had direct excitatory effects on larval motility. Although neuropeptide F is structurally analogous to neuropeptide Y, its mode-of-action in flatworms appears quite distinct from the common signalling mechanism seen in vertebrates. (C) 2003 on behalf of Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

Structure and magnetic properties of an unprecedented syn-antiμ-nitrito-1κO:2κO′ bridged Mn(iii)-salen complex and its isoelectronic and isostructural formate analogue

The preparation, crystal structures and magnetic properties of two new isoelectronic and isomorphous formate-and nitrite-bridged 1D chains of Mn(III)-salen complexes, [Mn(salen)(HCOO)](n) (1) and [Mn(salen)(NO2)](n) (2), where salen is the dianion of N,N'-bis(salicylidene)-1,2-diaminoethane, are presented. The structures show that the salen ligand coordinates to the four equatorial sites of the metal ion and the formate or nitrite ions coordinate to the axial positions to bridge the Mn(III)-salen units through a syn-anti mu-1 kappa O:2 kappa O' coordination mode. Such a bridging mode is unprecedented in Mn(III) for formate and in any transition metal ion for nitrite. Variable-temperature magnetic susceptibility measurements of complexes 1 and 2 indicate the presence of ferromagnetic exchange interactions with J values of 0.0607 cm(-1) (for 1) and 0.0883 cm(-1) (for 2). The ac measurements indicate negligible frequency dependence for 1 whereas compound 2 exhibits a decrease of chi(ac)' and a concomitant increase of chi(ac)'' on elevating frequency around 2 K. This finding is an indication of slow magnetization reversal characteristic of single-chain magnets or spin-glasses. The mu-nitrito-1 kappa O:2 kappa O' bridge seems to be a potentially superior magnetic coupler to the formate bridge for the construction of single-molecule/-chain magnets as its coupling constant is greater and the chi(ac)' and chi(ac)'' show frequency dependence.

U-Pb zircon and (40)Ar-(39)Ar K-feldspar dating of syn-sedimentary volcanism of the Neoproterozoic Marica Formation: constraining the age of foreland basin inception and inversion in the Camaqua Basin of southern Brazil

New U-Pb zircon and (40)Ar-(39)Ar K-feldspar data are presented for syn-sedimentary volcanogenic rocks from the Neoproterozoic Marica Formation, located in the southern Brazilian shield. Seven (of nine) U-Pb sensitive high-resolution ion microprobe analyses of zircons from pyroclastic cobbles yield an age of 630.2 +/- 3.4 Ma (2 sigma), interpreted as the age of syn-sedimentary volcanism, and thus of the deposition itself. This result indicates that the Marica Formation was deposited during the main collisional phase (640-620 Ma) of the Brasiliano II orogenic system, probably as a forebulge or back-bulge, craton-derived foreland succession. Thus, this unit is possibly correlative of younger portions of the Porongos, Brusque, Passo Feio, Abapa (Itaiacoca) and Lavalleja (Fuente del Puma) metamorphic complexes. Well-defined, step-heating (40)Ar-(39)Ar K-feldspar plateau ages obtained from volcanogenic beds and pyroclastic cobbles of the lower and upper successions of the Marica Formation yielded 507.3 +/- 1.8 Ma and 506.7 +/- 1.4 Ma (2 sigma), respectively. These data are interpreted to reflect total isotopic resetting during deep burial and thermal effects related to magmatic events. Late Middle Cambrian cooling below ca. 200 degrees C, probably related to uplift, is tentatively associated with intraplate effects of the Rio Doce and/or Pampean orogenies (Brasiliano III system). In the southern Brazilian shield, these intraplate stresses are possibly related to the dominantly extensional opening of a rift or a pull-apart basin, where sedimentary rocks of the Camaqua Group (Santa Barbara and Guaritas Formations) accumulated.

Vem bestämmer? : en undersökning av elevers uppfattning av informellt inflytande i gymnasieskolan

Syftet med detta examensarbete har varit mångfacetterat. Vi har undersökt om hur eleverna upplever det informella inflytandet över utbildningen på sina program, generellt sett och i samhällskunskap A. I detta har vi även undersökt skillnader mellan mäns och kvinnors uppfattning av inflytande i detta. Vidare har vi undersökt om eleverna ansett sig ha elevinflytande, och om de är nöjda med inflytandet på sin utbildning. Slutligen är syftet att skapa en modell för utvärdering av elevinflytande.Undersökningen är baserad på en enkätundersökning, som vi har genomfört på fyra program, på en gymnasieskola i Mellansverige. Programmen har varit El-, Handels, Medie- och samhällsprogrammet. Vi har avgränsat oss till det så kallade informella inflytandet, som har att göra med elevens inflytande över undervisningen, genom till exempel planering, genomförande och utvärdering. I vår undersökning har vi undersökt kategorierna: Innehåll i undervisningen, arbetsform, läromedel samt examinationssätt.Undersökningen påvisar att eleverna, i majoritet, anser att de har inflytande över sin utbildning. Vidare så anser en majoritet av eleverna, utom i Handelsprogrammet, att de är nöjda med inflytandet på utbildningen. Vi har dock kommit fram till att eleverna, generellt sett på utbildningen, upplever att det informella inflytandet är svagt och/eller gränsande mot mycket svagt informellt inflytande, i de olika kategorier som vi undersökt. Resultatet visar också, angående kursen samhällskunskap A, även där är svagt och/eller mycket svagt gällande det informella inflytandet, i de olika kategorier som vi undersökt.Vidare så har kommit fram till att det finns ett genusperspektiv, gällande det informella elevinflytandet. Skillnaderna mellan könen är att männen anser sig ha mest att säga till om gällande arbetsform och läromedel och minst om examinationssätt och innehåll i undersvingen, generellt sett på programmen. Medans kvinnorna enbart anser att de har mest inflytande över läromedel och minst över innehållet i undervisningen, generellt sett på programmen. Gällande samhällskunskap A, så anser männen att de har mest inflytande över arbetsform, och minst över examinationssätt. Medans kvinnorna ansett sig ha mest över innehåll i undervisningen och minst över examinationssätt. Männen och kvinnorna har dock den likheten, att de i samtliga kategorier anser att elevernas upplevelse av det informella inflytandet, är att det både generellt sett och i kursen samhällskunskap A är svagt och/eller mycket svagt.

Praxis och perception : En studie av gymnasieelevers tolkning av två lärares undervisningsmetoder i historia

Syftet med detta arbete är att ta reda på i vilken utsträckning och på vilket sätt lärarens undervisningspraxis styr gymnasieelevers syn på historieämnet. I samband med att vedertagna uppfattningar om kunskap och kunskapsöverföring har utmanats inom pedagogisk forskning, har historieämnet alltmer kommit att definieras som ett instrument för självinsikt och förståelse för omvärlden. Den förändrade historiesynen medför nya typer av undervisningspraxis bland enskilda lärare, där till exempel kronologi och kanon får stå tillbaka för bland annat tematisk fördjupning och flerperspektivism.Undersökningen består av intervjuer med två gymnasieklasser och deras gymnasielärare. I intervjuerna fick lärarna och eleverna var för sig definiera momentet utifrån vad det handlade om, vilka målsättningar man haft, hur undervisningen gått till och vad övningarna syftat till.Resultaten visar att lärarnas respektive historiesyn och undervisningspraxis i mycket stor utsträckning präglar elevers perception av historieämnet. Elevernas normer och målsättningar i relation till historieundervisningen följde respektive lärares undervisningspraxis, utan att andra faktorer, som läromedel, i nämnvärd utsträckning spelade in. Läraren framstår därmed som den klart viktigaste auktoriteten för elevernas förståelse av historieämnet.

Rättvis bedömning? : - om elevers och lärares uppfattning om betygsättning i matematik på gymnasiet

I detta arbete undersökes främst gymnasieelevers och gymnasielärares uppfattning om rättvise- och rättsäkerhet gällande betygsättning inom matematik. Resultatet är att lärarna i sina uppfattningar bekräftar de i annan forskning nämnda orsakerna till orättvisor inom betygsättning, som: betygsinflation, att elever kan "utnyttja systemet", att vad lärarkonstruerade prov mäter kan variera mycket, nivågrupperingar och programtillhörighet, "luddiga" styrdokument, felaktigheter i betygsbedömningar, personkemi och sist men inte minst brist på kommunikation mellan lärare, ledning och olika skolor. Elever verkar dock uppfatta systemet som i stort rättvis, eller så rättvist det kan vara med tanke på att den mänskliga faktorn. De verkar dessutom främst fokusera sig på orättvisor på detaljnivå och inte på systemnivå. Varken elever eller lärare verkar finna några större problem angående rättsäkerheten gällande betygsättning.