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SUMMARYBackgroundSOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralizing antibodies.MethodsFrom March 8th to September 30th, 2021 we conducted in Havana, Cuba a multicentre randomized, double-blind, placebo-controlled, phase-3 trial evaluating two doses of SOBERANA-02 and a heterologous scheme with one dose SOBERANA-Plus added to it. Participants 19–80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 occurring at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose.FindingWe included 44·031 participants in a context of Beta VOC predominance, with this variant being gradually replaced by Delta near the trial end. Vaccine efficacy in the heterologous combination was 92·0% (95%CI 80·4–96·7) against symptomatic and 100% against severe COVID-19. Two doses of SOBERANA-02 was 69·7% (95%CI 56·5-78·9) and 74·9% (95%CI 33·7-90·5) efficacious to protect against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe AEs was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.InterpretationOur results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC dominance and that they constitute an attractive, feasible option for low- and middle-income countries, where besides financial constraints ease of vaccine storage and distribution is of concern.FundingThis study received funds from Finlay Vaccine Institute and National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020–20). of Ministry of Science, Technology and the Environment (Contract Project-2020-20) in Cuba.

p27 is an antigenic protein produced by Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis (PCM). Despite its unknown function, it has been suggested as a putative virulence factor, proposed as a suitable target for the design of diagnostic tools and vaccines, and considered as an enhancer in antifungal treatment of PCM. We evaluated sequence polymorphisms of PbP27 gene sequence among isolates, finding some polymorphisms associated with the isolates' phylogenetic origin. In order to determine if there was a differential expression pattern between morphological states and among isolates, we also evaluated PbP27 expression, at transcriptional and translational levels, in mycelia and yeast cultures in 14 isolates belonging to the P. brasiliensis species complex (S1, PS2, PS3, and 'Pb01-like', proposed to be named Paracoccidioides lutzii) by two techniques, real time RT-PCR (RT-qPCR) and protein dot blot. For the latter, four protein extracts from different cell localizations (SDS or ?-mercaptoethanol, cytoplasmic and extracellular proteins) were analyzed for each isolate. p27 was present in the four extracts evaluated, mainly in the SDS extract, corresponding to an extract containing proteins loosely attached to the cell wall. This information correlates with immunohistochemical analysis, where positive staining of the yeasts' cell wall was observed. We found that p27 was present in all isolates, mainly in the yeast form. This pattern was corroborated by RT-qPCR results, with higher expression levels found in the yeast form for most of the isolates. The results provide new insights into the expression patterns of this protein, and further characterize it in view of potential uses as a diagnostic and/or therapeutic tool. © 2011 Elsevier Inc.

2-Aminoethanol and C-substituted derivatives 1 react with diacetyl, benzil, and 1-phenyl-1,2-propanedione, models of α-diketones 2 to give with remarkable regio- and stereoselectivity 2-hydroxy-5,6-dihydro-2H-1,4-oxazines 3, cis-octahydro[1,4]oxazino[3,2-6]oxazines 4, α-imino ketones 6, 2-acetyl-1,3-oxazolidines 7, N,N′-bis(2-hydroxy-2-methylpropyl)-2,3-butanediimines 8, and 2,2′-dimethyl-2,2′-bioxazolidines 9 depending on the nature of the reagents and the reaction conditions. On the basis of isolated intermediates, a reasonable mechanism taking into account the stereoelectronic effects observed on the cyclization has been proposed for these processes. In addition, a kinetic study of the ring-chain-ring tautomeric equilibrium of oxazines 3a-c, 3i-k, and 3o-q has been studied by 1H NMR and 13C NMR. In solution, compounds 3a-c and 3i-k exhibit a three-component tautomeric equilibria consisting of the following: the β-iminohemiacetal 3, the β-hydroxyimino ketone 6, and the 2-acetyl- or 2-benzoyl-1,3-oxazolidine 7. The calculated rate constants for this process show that the equilibrium is shifted toward the formation of the five-membered ring by 0.4-4.8 kJ mol-1 over the six-membered ring depending on the substitution patterns. Compounds 3p-q exist in solution as equimolar mixtures of the ring and open-chain tautomers. Compound 3o exists predominantly in the open-chain form. In addition, 2-acylthiazolidines 13a-c do not evidence any dynamic processes in solution. © 1992 American Chemical Society., The research presented in this paper has been financially supported by DGICYT (PB90-0047), MEC-Spain.

We gratefully acknowledge financial support from the Comision Asesora de Investigacion Cientifica y Tecnica (Spain).

5 pags., 3 figs., 8 tbs., In a previous paper (1) we carried out a comparative study between the physicochemical properties of 1,2,6-thiadiazine 1,l-dioxide derivatives and related pyrazoles. We have now extended the comparison to compounds of this series with antiinflammatory activity. Thus, we now wish to report the physico-chemical properties and preliminary biological screening of 1,2,6-thiadiazin-3,5(2H,6H)-dione 1,l-dioxides 1 (2), 2 and 3 (3), structurally related to phenylbutazone 4. Compound 3 can be considered as pyrazolidindione 4 in which an SO2 group has been introduced between the two nitrogen atoms. Thiadiazine derivatives 1 and 2 have been chosen because the cyclohexyl moiety seems to be useful for inducing antiinflammatory activity (4-6). Thus, whilst 1,2-dicyclohexyl pyrazole derivatives have shown some activity (7), the corresponding cyclopentyl compounds turned out to be inactive (8)., The financial support of the Comisión Asesora de Investigaci6n Cientifica y Técnica (CAICYT) of Spain is gratefully acknowledged. The authors wish to thank Prof. Dr. W. Pfleiderer for the determination of the pK, values.

Complexes of the general formulae [Ru(diamine)(PPh 3 )(η-C 5 H 5 )]ClO 4 and [Ru(diolefin)(PPh 3 )(η-C 5 H 5 )]ClO 4 (diamine = ethylenediamine (en), propylenediamine (pn), 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), biimidazole (H 2 bim), bibenzimidazole (H 2 bbzim) and 2-(2′-pyridylbenzimidazole) (Hpybzim); diolefin = 2,5-norbornadiene (nbd), tetrafluorobenzobarrelene (tfb)) have been made by reaction of the complex RuCl(PPh 3 ) 2 (η-C 5 H 5 ) with the diamine or diolefin in the presence of sodiuim perchlorate. A single-crystal X-ray diffraction study of [Ru(nbd)(PPh 3 )(η-C 5 H 5 )]ClO 4 has been carried out. Crystals of the complex are monoclinic, space group P 2 1 / n , with a 18.0576(5), b 14.5070(3), c 10.3186(3) A; β 103.20(6)°. The structure was solved by Patterson synthesis using 4209 observed reflections (2σ( I ) criterion) and refined to a R factor of 0.040. Reaction of RuCl(PPh 3 ) 2 (η-C 5 H 5 ) with oxygen in the presence of sodium perchlorate leads to oxidation of the coordinated triphenylphospine ligands giving the complex [Ru{(η 6 -C 6 H 5 )Ph 2 PO}η-C 5 H 5 )]ClO 4 . In order to establish the structural identity of this compound a single-crystal X-ray diffraction study has been made. Crystals of this complex are monoclinic, space group P 2 1 / c , with a 10.818(5), b 9.4480(3), c 21.0036(19) A; β 90.246(6)°. The structure was solved by Patterson synthesis using 3819 observed reflections (3σ( I ) criterion) and refined to a R factor of 0.036. The ruthenium atom is coordinated in a sandwich fashion by the cyclopentadienyl group and a phenyl ring of the triphenylphosphine oxide ligand. The synthesis of new heteronuclear ruthenium(II)-rhodium(I) complexes of formulae [(η-C 5 H 5 )(Ph 3 P)-Ru(μ-bim)RhY 2 ] x and (η-C 5 H 5 )(Ph 3 P)Ru(μ-bbzim)RhY 2 (Y = CO, Y 2 = diolefin) is also described.

Krohnke condensation of several cycloimmonium salts with p-dimethylaminobenzaldhyde has been studied. X-Ray diffraction, IR and Raman spectra, 1H-and 13C-NMR and UV spectra of the products are discussed, being compared, when necessary, with the starting pyridinium salts. All compounds showed the Z configuration, corresponding to the more stable structure, except one, in which steric factors were predominant.

Single crystals of 3Bi2O3:5B2O3 have been obtained from the melt and subsequent devitrification of the glassy compound, at 450°C during 90 hr. The compound is orthorhombic, space group Pnma with two formula units in the cell. The lattice parameters are a = 6.532 A, b = 7.733 A, c = 18.566 A. The structure was solved from a complete set of three-dimensional MoKα diffractometer data, the final R being 0.097. The structure is made up of Bi3+ cations and O2− and (B5O11)7− anions. The pentaborate anion is formed by two BO4 tetrahedra and three BO3 triangles, sharing edges and corners. An oxygen that is not bonded to any boron is in the center of a three-bismuth triangle. Two independent bismuth atoms are present in the structure. Bi(1) has six first-neighbor oxygens with an average BiO distance of 2.44 A and Bi(2) has either six or seven oxygens in the first coordination sphere with an average BiO distance of 2.43 or 2.80 A, respectively.

Cristallisation dans le systeme triclinique, groupe P1 et affinement de la structure jusqu'a R=0,077. Distorsion du cycle cyclooctene

The infrared and 1H and 13C NMR spectra of 3-aza-bicyclo[3.2.1]octane-8-β-ol have been examined in several media. To assist in interpretation of the spectroscopic data, the crystal structure has been determined by X-ray diffraction. The bicyclic system adopts a chair-envelope conformation with OH and phenethyl groups, respectively, in axial and equatorial positions with respect to the piperidine ring. The crystal structure is stabilized by means of OH...N intermolecular hydrogen bonding. In CCl4 solution the initial chair-envelope conformation changes to a boat-envelope conformation which is stabilized by an intramolecular hydrogen bond. The unambiguous assignment of all protons of the bicyclic system, not previously described, has also been carried out. © 1987., We thank A. Gómez Morilla, Instituto de Estructura de la Materia, C. S. I. C., Madrid for recording 360 MHz ‘H NMR spectra, A. Torossian, Bruker Analytische Messtechnik GMBH, for the spectra registered at 500 MHz, and the Comisión Asesora de Investigación Científica y Técnica (Grant 1750/ 82) for partial support of this research.

This structure determination is part of a study being carried out in this laboratory on heterocyclic spirohydantoin derivatives with pharmacological properties. The present compound was obtained by Trigo, Galvez & Avendafio (1978). The results of proton N M R studies seemed consistent with an adamantanelike structure, in agreement with Douglass & Ratliff (1968), Fig. 1. Support for this structure was derived from the position of the N-methyl resonance. However, the same authors admit that this fact does not constitute a definitive proof of this supposition. The present investigation was performed in order to verify the above statement and to elucidate the structure in the solid state.

X-ray analysis of 2,3-dimethylnaphthazarin (C 12 H 10 O 4 ) has been carried out from three dimensional diffractometer data and refined to an R -factor of 0.053 with ω = 1.0 for 1278 observed reflections. The compound crystallizes in the P 2 1/a space group, with a monoclinic cell of dimensions α = 16.429 (4), b = 6.524 (1), c = 9.136 (4), A, β = 90.19 (2)° and four molecular formulae in the unit cell. The crystal is built from molecules stacked up the c axis and the dimethylnaphthazarin molecules overlap to form a charge-transfer complex. Moreover, naphthazarin and methylnaphthazarin derivatives are examined as charge-transfer complexes.

The reactions of palladium(II) chloride with 1,4 - diphenyl - 2,3 - dimethyl - 1,4 - diazabutadiene and 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene are described. With 1,4 - diphenyl - 2,3 - dimethyl - 1,4 - diazabutadiene diimine fission is produced, giving rise to a product identified by elemental analysis, IR and Raman spectra, and X-ray diffraction, as trans-dichlorobis(aniline) palladium(II). The complex is soluble in dimethylformamide and crystallizes with two molecules of solvent. The substance crystallizes in the monoclinic space group P21/n. The X-ray data were refined to R = 0.047 and Rw = 0.046. Final distances are Pd N = 2.060(5)Aand Pd C1 = 2.299(2)A. There are two bifurcated intermolecular N H ... C1 and C H... C1 hydrogen bonds which, together with one more intermolecular hydrogen bond N H... O, are responsible for the packing of the molecules. However, when 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene was treated with palladium chloride under the same conditions cis - dichloro - 1,4 - di(p - methoxyphenyl) - 2,3 - dimethyl - 1,4 - diazabutadiene was formed, as deduced from elemental analysis, and IR and Raman spectra.

The crystal structure and single-crystal ac magnetic susceptibilities of KMnF 4 ·H 2 O are reported. The structure, which is isomorphous to that of RbMnF 4 ·H 2 O, consists of chains of alternating trans-[ MnF 4 F 2 2 ] 2− and trans-[ MnF 2 F 2 2 ( H 2 O ) 2 ] tetragonally elongated octahedra connected to each other by shared apical fluorine atoms. Crystal data: Space group C2 c , a = 13.907(1) A, b = 6.2136(2) A, c = 10.492(1)A, β = 104.69(1)°, V = 877.0(2) A 3 , D c = 2.85 g cm −3 , Z = 8, R = 0.044. Magnetic susceptibility measurements show a broad maximum around 52 K indicative of lower dimensionality behavior. The data may be fit to a Heisenberg S = 2 linear chain model with J k B = −6.5 K and g = 2.05. At 8.45 K a sharp peak in the susceptibility data parallel to the chains indicates weak ferromagnetic behavior.

The title compound, (C6H8N)4[Mo8O26], has been prepared and its crystal structure determined by X-ray crystallography. The compound is triclinic,P¯1,Z=1 witha=10.167(1),b=10.745(1),c=10.027(8) A,α=85.05(1),β=106.73(3), λ=107.75(1)°,V=999.1(7) A3,F(000)=748,Dx=2.59 andDo=2.61(1) Mg/m3. The [Mo8O26]4− anion shows slight differences in several bond lengths and angles when compared with other related octamolybdates. The planar cations are connected to the polyanions through bifurcated hydrogen bonds. The MoO6 octahedra are distorted and the distortion has been evaluated using three different equations. The spectroscopic study shows that the cations are protonated and the polyanion presents the well-known infrared spectrum for octamolybdates.

A conformational study of the title compound has been carried out in solution and solid states. The molecules are packed in the crystal forming a charge-transfer complex, where two different molecular pairs are found. Visible spectra data show two weak absorption bands.

Crystals of 1,4-dichloro-7-methylpyrrolo[3,2-d]pyridazine,·C7H3N3Cl2, are monoclinic:a = 18.7465(9),b = 9.3031(3),c = 9.5363(3) A, β = 104.755(3) °,Z = 8,P21/n,D x = 1.667 g cm−3, μ(MoKα) = 7.4 cm−1. The structure was solved by Fourier techniques and refined toR = 0.042 for the observed reflections, and 0.060 for all data measured. The two independent molecules in the asymmetric unit have similar geometry. The packing in the crystal is due to van der Waals' forces and two hydrogen interactions of type N-H ⋯ N.

N -(8-Isopropyl-nortropan-3-α-yl)-2-methoxy-4-amino-5-chlorobenzamide has been synthesized and its crystal and molecular structures determined by X-ray diffraction, IR, 1 H-NMR and 13 C-NMR methods. The pyrrolidine and piperidine rings adopt a flattened N-8 envelope and distorted chair conformation puckered at N-8 and flattened at C-3 respectively, with the N -isopropyl substituent and the amido group in axial position with respect to the piperidine ring. A great predominance in solution of the conformer observed in the solid state is proposed.

The anilinium β-octamolybdate dihydrate has been prepared in acidic aqueous solution. TG, DTG, IR and 1H NMR techniques have been used to identify the compound. It belongs to a series of molybdates of alkyl-N- and -N,N-substituted anilinium cations. Single crystals have been analyzed by X-ray diffraction. Crystal data are: (C6H8N)4[Mo8O26] · 2H2O, space group P 1 , Z = 1, a = 10.007(1), b = 8.014(2), c = 14.645(8)A, α = 109.81(3), β = 108.59(2), γ = 85.44(2)°, V = 1052.9(6) A3, Do = 2.49(1), Dx = 2.52 mg m−3, R = 0.026 and Rw = 0.031 for 5297 observed reflexions. The crystal structure consists of discrete [β-Mo8O26]4− polyanions, two crystallographically independent (C6H8N)+ cations and one independent water molecule. Polyanions are linked to the cations and to the water molecules by hydrogen bonds of types NH…O and OH…O.

Mr = 460.36, monoclinic. P21/c, a = 13.718(1), b = 11.090(1), c = 14.985(1) Å, β = 98.162(2)°, V = 2256.67(9) Å3, Z = 4, Dx = 1.355 Mgm−3, μ = 0.933 mm−1, F(000) = 968, room temperature, final R = 0.047 (Rw = 0.048) for 3184 [I ⩾ 3 σ(I)] observed reflections. The title compound has the “three-legged piano stool” geometry, i.e. the coordination geometry of the iron can be regarded as a distorted octahedron with aη5 – C5Me5 group occupying three coordination sites. Like its nonmethylated analogue it contains an unusually monodentate dithiophosphate ester ligand.

N (8)-Ethylnortropane-3-spiro-5′-oxazolidine-2′-4′-dione hydrochloride has been synthesized and its crystal and molecular structures determined by X-ray diffraction. IR, Raman, 1 H NMR and 13 C NMR methods. It is found that the crystalline structure is maintained in D 2 O solution. In D 2 O solution a protonation equilibrium takes place and the percentages of the two isomers are calculated. In order to correlate the results, analogous spectroscopic measurements have also been made for the N -ethylnortropane-3-spiro-5′-oxazolidine-2′,4′-dione, for which a zwitterionic structure is deduced.

2-aminopyridinium heptamolybdate trihydrate crystallizes in the monoclinic system with space group P21/n and Z=4 (R=0.030). The unit cell dimensions area=14.8161(4) A,b=17.5073(4) A,c=20.8492(6) A, β=107.503(2)°, V=5157.7(2) A3. The [Mo7O24]6− anions in the 2-aminopyridinium, ammonium(4), guanidium(2), propyl- and isopropyl-ammonium(1) molybdates, while similar, show slightly differences in several bond lengths and angles. The distinguishing features of 2-aminopyridinium heptamolybdate trihydrate structure is its extensive hydrogen bonding. The planar cations and the water molecules are positioned so as to be able to form hydrogen bonds with either molybdate oxygen atoms or water oxygen atoms. Four different types of hydrogen bonds have been found-: N-H... O (mono- and bifurcated), N-H... Ow (monofurcated), Ow-Hw... O (mono- and bi-furcated) and Ow-Hw...OW (monofurcated). The closest approach distances associated with 27 of these potential hydrogen bonds vary from 2.67 to 3.24 A(7,8)). The proposed strong hydrogen bonding interactions appear to stabilize the structure and explain the way of three water molecules are lost upon heating. Some of these hydrogen bonds can play an important role in the possible photochromism of this compound.

The crystal structure of the title compound has been determined. MW = 248.315, the crystals are orthorhombic, space group Pnma with a = 15.695(9), b = 7.592(3), c = 8.508(3) Å, V = 1013.8(8) Å3, Z = 4, Dc = 1.627(3) Mg · m−3, μ = 8.550 mm−1, λCuKα, F(000) = 512. It was refined to R = 0.051, Rw = 0.054, for 846 unique observed reflections with I > 2 σ(I). The ion succinate lies on a mirror plane as well as the water molecules. The K+ ion is linked to six oxygen atoms in a distorted octahedral coordination with distances ranging from 2.716(3) to 3.070(4) Å. The molecules are linked by hydrogen bonds and coupled through potassiums ions forming layers at ¼ and ¾ of b.

The title compounds form part of a series of S-dioxo analogs of pyrimidines which could act as potential antimetabolites. C 3H2 N 305 S. N a ÷ . H20 was refined to R = 0.041 using 1945 independent reflexions; monoclinic, space group P21/e with Z = 4, a = 6.2914 (3), b = 14.001 (1), c--8.9204 (3)/k, f l= 95.382 (4) °. The refinement for C3H2N3OsS-. K + . H20 led to R = 0.039 for 2006 reflexions; monoclinic, space group P21/e with Z = 4, a = 6.0744(4), b = 18.533(2), c = 7.497 (1)/k, fl = 91.68 (1) °. The anion, formed by deprotonation of the title compound, acts as a bidentate ligand for Na ÷ ions giving rise to two identical N a O bonds of 2.40/k. In the potassium salt, however, those K O distances are unequal, 2.88 and 3.17/k (10% elongated) and so the anion seems to behave as a monodentate ligand. The Na ÷ ions are octahedrally coordinated, with distances ranging from 2.34 to 2.49/k. The K ÷ ions are mainly surrounded by seven neighbours at distances in the range 2.78 to 3.01/k, forming a laterally capped trigonal prism. The observed N a O bond lengths agree with the expected distances for an interaction model of cation-dipole type. The observed K O distances are, however, elongated 7% with respect to the expected ones. These observations could be related to the different cationic changeability presented by these compounds. Strong electron modifications are found within the thiadiazine rings of these salts when compared with the free heterocyclic compound. Proton migration occurs within the thiadiazine rings during the formation of both salts. Dimeric anions are formed through two centrosymmetric hydrogen bonds.

The structure of DAG has been determined from three-dimensional diffractometer data by direct methods with the tangent formula. The space group is P21 with a = 11.3328 (17), b=6.1197 (4), c-8-2568 (11)/~, fl= 103.44 (1) °. The molecule has an anhydro bridge across the galactose moiety forming a five-membered ring which has an envelope conformation while the pyranose ring has a strained chair conformation. An intermolecular hydrogen bond (2.864 A) occurs between the hydroxyl group and the O atom of the bridge.