Selective Formation of Pd-DNA Hybrids Using Tailored Palladium-Mediated Base Pairs: Towards Heteroleptic Pd-DNA Systems.

The formation of highly organized metal-DNA structures has significant implications in bioinorganic chemistry, molecular biology and material science due to their unique properties and potential applications. In this study, we report on the conversion of single-stranded polydeoxycytidine (dC15 ) into a Pd-DNA supramolecular structure using the [Pd(Aqa)] complex (Aqa=8-amino-4-hydroxyquinoline-2-carboxylic acid) through a self-assembly process. The resulting Pd-DNA assembly closely resembles a natural double helix, with continuous [Pd(Aqa)(C)] (C=cytosine) units serving as palladium-mediated base pairs, forming interbase hydrogen bonds and intrastrand stacking interactions. Notably, the design of the [Pd(Aqa)] complex favours the interaction with cytosine, distinguishing it from our previously reported [Pd(Cheld)] complex (Cheld=chelidamic acid). This finding opens possibilities for creating heteroleptic Pd-DNA hybrids where different complexes specifically bind to nucleobases. We confirmed the Pd-DNA supramolecular structural assembly and selective binding of the complexes using NMR spectroscopy, circular dichroism, mass spectrometry, isothermal titration calorimetry, and DFT calculations.

Single-Stranded DNA as Supramolecular Template for One-Dimensional Palladium(II) Arrays.

Atomic-level control over the position and growth of a single and continuous metal chain is an ambitious goal that often requires complex and costly processes. Herein, we demonstrate that 1Pd-DNA molecules, comprising a continuous single chain of PdII ions, can be prepared by a simple self-assembly reaction between the complex [Pd(Cheld)(CH3 CN)] (1Pd_CH3 CN) (Cheld=chelidamic acid) and single-stranded DNA homopolymers (ss-DNA) containing adenine (A) or 7-deazaadenine (X) bases. The single PdII -base pairs [1Pd(N1-A)] and [1Pd(N1-X)] were synthesized and characterized in solution and solid-state (X-ray diffraction) revealing an arrangement similar to that of natural Watson-Crick base pairs. Subsequently, 1Pd-DNA hybrids were prepared, characterized, and their structures studied by small-angle X-ray scattering (SAXS) and ab-initio calculations. The results indicate that the 1Pd-DNA structures resemble that of double-stranded DNA, with one strand being replaced by a supramolecular stack of continuous PdII complexes.

Comparative Structural Study of Metal-Mediated Base Pairs Formed outside and inside DNA Molecules.

The formation of copper(II)-mediated base pairs involving pyridine-2,6-dicarboxylate derivatives and canonical nucleosides has proven to be a smart approach to introduce copper(II) ions at specific locations of DNA duplexes. However, the structural characteristics of these metalized base pairs have not yet been revealed, and their effect on DNA structures is difficult to assess. Herein, for the first time, we report on the different structural details of copper-mediated base pairs formed by themselves and in DNA duplexes. The individual base pairs [Cu(mcheld)(N3-Cyt)(H2O)]·3H2O (1Cu_Cyt), [Cu(mcheld)(N7-Ade)(H2O)2]·2H2O (1Cu_Ade), [Cu(mcheld)(N7-Gua)(H2O)] (1Cu_Gua), and [Cu(mcheld)(N1-7CAde)(H2O)]·H2O (1Cu_7CAde) were obtained from the reaction of the metal complex [Cu(mcheld)(H2O)2] (1Cu) (mcheld = 4-methoxypyridine-2,6-dicarboxylic acid) with model nucleosides (Cyt = N1-methylcytosine, Ade = N9-ethyladenine, Gua = N9-propylguanine, 7CAde = N9-propyl-7-deazaadenine). The crystal structure of the five complexes was determined by means of single-crystal X-ray diffraction. Furthermore, the formation of the 1Cu_Cyt and 1Cu_Gua base pairs in the middle of DNA duplexes, duplex DNA15 (917 atoms) and DNA10 (649 atoms), respectively, was studied using highly demanding ab initio computational calculations. These theoretical studies aimed to validate, from a structural point of view, whether base pairs of the kind 1Cu_nucleosides can be included in a DNA double helix and how this situation affects the double-helical structure. The results indicate that the 1Cu_Cyt and 1Cu_Gua base pairs can be formed in a DNA molecule without significant structural constraints. In addition, the double-helix DNA structure remains virtually unchanged when it contains these Cu(II)-mediated base pairs.

Silver(I)-Mediated Base Pairs in DNA Sequences Containing 7-Deazaguanine/Cytosine: towards DNA with Entirely Metallated Watson-Crick Base Pairs.

DNA sequences comprising noncanonical 7-deazaguanine (7C G) and canonical cytosine (C) are capable of forming Watson-Crick base pairs via hydrogen bonds as well as silver(I)-mediated base pairs by coordination to central silver(I) ions. Duplexes I and II containing 7C G and C have been synthesized and characterized. The incorporation of silver(I) ions into these duplexes has been studied by means of temperature-dependent UV spectroscopy, circular dichroism, and DFT calculations. The results suggest the formation of DNA molecules comprising contiguous metallated 7C G-AgI -C Watson-Crick base pairs that preserve the original B-type conformation. Furthermore, additional studies performed on duplex III indicated that, in the presence of AgI ions, 7C G-C and 7C A-T Watson-Crick base pairs (7C A, 7-deazadenine; T, thymine) can be converted to metallated 7C G-AgI -C and 7C A-AgI -T base pairs inside the same DNA molecule whilst maintaining its initial double helix conformation. These findings are very important for the development of customized silver-DNA nanostructures based on a Watson-Crick complementarity pattern.

Highly Stable Double-Stranded DNA Containing Sequential Silver(I)-Mediated 7-Deazaadenine/Thymine Watson-Crick Base Pairs.

The oligonucleotide d(TX)9 , which consists of an octadecamer sequence with alternating non-canonical 7-deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double-stranded DNA through the formation of hydrogen-bonded Watson-Crick base pairs. dsDNA with metal-mediated base pairs was then obtained by selectively replacing W-C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag(+) ions, and its stability is significantly enhanced in the presence of Ag(+) ions while its double-helix structure is retained. Temperature-dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)-mediated base pairs. This strategy could become useful for preparing stable metallo-DNA-based nanostructures.

Mechanism of formation of supramolecular DNA-templated polymer nanowires.

Details of the mechanism of formation of supramolecular polymer nanowires by templating on DNA are revealed for the first time using AFM. Overall these data reveal that the smooth, regular, structures produced are rendered by highly dynamic supramolecular transformations occurring over the micrometre scale. In the initial stages of the process a low density of conducting polymer (CP) binds to the DNA as, essentially, spherical particles. Further reaction time produces DNA strands which are more densely packed with particles giving a beads-on-a-string appearance. The particles subsequently undergo dynamic reconfiguration so as to elongate along the template axis and merge to yield the highly regular, smooth morphology of the final nanowire. MD simulations illustrate the early stages of the process showing the binding of globular CP to duplex DNA, while the latter stages can be modeled effectively by a linear thermodynamic description based on the balance between the line energy, which accounts for adhesion of the material to the template, and its surface tension. This model accounts for the phenomena observed in the AFM studies: the relative success of DNA templating of polymers compared to metals; the slow approach to equilibrium; and the observed thinning and 'necking' phenomena as the structures transform from beads-on-a-string to smooth nanowire.

Unveiling the solution structure of a DNA duplex with continuous silver-modified Watson-Crick base pairs.

The challenge of transforming organized DNA structures into their metallized counterparts persists in the scientific field. In this context, utilizing DNA molecules modified with 7-deazapurine, provides a transformative solution. In this study, we present the solution structure of a DNA duplex that can be transformed into its metallized equivalent while retaining the natural base pairing arrangement through the creation of silver-modified Watson-Crick base pairs. Unlike previously documented X-ray structures, our research demonstrates the feasibility of preserving the intrinsic DNA self-assembly while incorporating AgI into the double helix, illustrating that the binding of silver does not disrupt the canonical base-pairing organization. Moreover, in our case, the uninterrupted AgI chain deviates from forming conventional straight linear chains; instead, it adheres to a helical arrangement dictated by the underlying DNA structure. This research challenges conventional assumptions and opens the door to precisely design structures based on the organization of highly stable Ag-DNA assemblies.

Coordination chemistry of 6-thioguanine derivatives with cobalt: toward formation of electrical conductive one-dimensional coordination polymers.

In this work we have synthetized and characterized by X-ray diffraction five cobalt complexes with 6-thioguanine (6-ThioGH), 6-thioguanosine (6-ThioGuoH), or 2'-deoxy-6-thioguanosine (2'-d-6-ThioGuoH) ligands. In all cases, these ligands coordinate to cobalt via N7 and S6 forming a chelate ring. However, independently of reagents ratio, 6-ThioGH provided monodimensional cobalt(II) coordination polymers, in which the 6-ThioG(-) acts as bridging ligand. However, for 2'-d-6-ThioGuoH and 6-ThioGuoH, the structure directing effect of the sugar residue gives rise to mononuclear cobalt complexes which form extensive H-bond interactions to generate 3D supramolecular networks. Furthermore, with 2'-d-6-ThioGuoH the cobalt ion remains in the divalent state, whereas with 6-ThioGuoH oxidation occurs and Co(III) is found. The electrical and magnetic properties of the coordination polymers isolated have been studied and the results discussed with the aid of DFT calculations, in the context of molecular wires.

Synthesis, characterisation and electrical properties of supramolecular DNA-templated polymer nanowires of 2,5-(bis-2-thienyl)-pyrrole.

Supramolecular polymer nanowires have been prepared by using DNA-templating of 2,5-(bis-2-thienyl)-pyrrole (TPT) by oxidation with FeCl(3) in a mixed aqueous/organic solvent system. Despite the reduced capacity for strong hydrogen bonding in polyTPT compared to other systems, such as polypyrrole, the templating proceeds well. FTIR spectroscopic studies confirm that the resulting material is not a simple mixture and that the two types of polymer interact. This is indicated by shifts in bands associated with both the phosphodiester backbone and the nucleobases. XPS studies further confirm the presence of DNA and TPT, as well as dopant Cl(-) ions. Molecular dynamics simulations on a [{dA(24):dT(24)}/{TPT}(4)] model support these findings and indicate a non-coplanar conformation for oligoTPT over much of the trajectory. AFM studies show that the resulting nanowires typically lie in the 7-8 nm diameter range and exhibit a smooth, continuous, morphology. Studies on the electrical properties of the prepared nanowires by using a combination of scanned conductance microscopy, conductive AFM and variable temperature two-terminal I-V measurements show, that in contrast to similar DNA/polymer systems, the conductivity is markedly reduced compared to bulk material. The temperature dependence of the conductivity shows a simple Arrhenius behaviour consistent with the hopping models developed for redox polymers.

Pyrrolyl-, 2-(2-thienyl)pyrrolyl- and 2,5-bis(2-thienyl)pyrrolyl-nucleosides: synthesis, molecular and electronic structure, and redox behaviour of C5-thymidine derivatives.

A series of modified nucleosides based on thymidine have been prepared by Pd-catalysed cross-coupling between N-alkyl-alkynyl functionalised pyrrolyl- (py), 2-(2-thienyl)pyrrolyl- (tp) or 2,5-bis(2-thienyl)pyrrolyl (tpt) groups with 5-iodo-2'-deoxyuridine. The length of the alkyl chain linking the nucleoside and pyrrolyl-containing unit, N(CH(2))(n)C[triple bond, length as m-dash]C-nucleoside (where n = 1-3) was also varied. The compounds have been characterised by (1)H NMR, ES-MS, UV-vis, cyclic voltammetry (CV) and, in some cases, single-crystal X-ray diffraction. Cyclic voltammetry studies demonstrated that all the py-, tp- and tpt-alkynyl derivatives 1-7 can be electrochemically polymerised to form conductive materials. It was found that increasing the N-alkyl chain length in these cases resulted in only minor changes in the oxidation potential. The same behaviour was observed for the tp- and tpt-modified nucleosides 9-12; however, the py-derivative, 8, produced a poorly conducting material. DFT calculations on the one-electron oxidised cation of the modified nucleosides bearing tp or tpt showed that spin density is located on the pyrrolyl and thienyl units in all cases and that the coplanarity of adjacent rings increases upon oxidation. In contrast, in the corresponding pyrrolyl cases the spin density is distributed over the whole molecule, suggesting that polymerisation does not occur solely at the pyrrolyl-Cα position and the conjugation is interrupted.

Self-assembly of a bis(adeninyl)-Cu(I) complex: a cationic nucleobase duplex mimic.

The tetrahedral bis(adeninyl)-Cu(I) complex, , self-associates in polar solvent through complementary hydrogen-bonding interactions and appears to mimic the natural assembly of duplex DNA.

Reactions of Pd(II) with chelate-tethered 2,6-diaminopurine derivatives: N3-coordination and reaction of the purine system.

Alkyldiamine-tethered derivatives of 2,6-diaminopurine, ethylenediamine-N9-propyl-2,6-diaminopurine, L1, and ethylenediamine-N9-ethyl-2,6-diaminopurine, L2, react with Pd(II) to give N3-coordinated complexes. However, the exact nature of the resulting complex is dependent on the reaction conditions. With PdCl(2)(MeCN)(2) in MeCN/H(2)O the expected [PdCl(N3-2,6-DAP-alkyl-en)](+) complex, 1, is formed with L1 chelating the metal center in a tridentate manner through the diamine function and N3 of the purine base. However, under the same conditions the shorter, ethyl-tethered, L2 gives a complex dication, 2, containing a tetradentate ligand forming simultaneously 5-, 6-, and 7-membered chelate rings. This resulting acetamidine, derived by addition to coordinated MeCN, appears to be the first such case involving the 2-amino group of a purine. The ethyl-analogue of 1, [PdCl(N3-2,6-DAP-Et-en)](+) 3, was prepared by reaction of L2 with K(2)PdCl(4) in aqueous media.

Probing metal-ion purine interactions at DNA minor-groove sites.

The effect of the 2-amino group on metal ion binding at the N3-position of a purine base has been investigated using chelate-tethered derivatives. Reactions of diamine-tethered 2,6-diaminopurine (DAP) with divalent d-block metal ions Cu(II) and Cd(II) confirm that binding can occur, but this is much less prevalent than with adenine. In this regard DAP is similar to guanine where we have previously observed a general lack of N3-binding by divalent metal ions compared to adenine (e.g., Houlton et al., Angew. Chem., Int. Ed. 2000, 39, 2360; Chem.-Eur. J. 2000, 6, 4371). For the univalent d-block metals ions, Cu(I) and Ag(I), binding to adenine N3 is not observed in the solid state, as shown by reactions with dithioether-tethered adenine derivatives. Instead, depending on stoichiometry of the reaction, discrete (with metal/ligand ratio 1:2) or polymeric (with metal/ligand ratio 1:1) complexes were isolated and characterized by single crystal X-ray methods. In the former the nucleobases are pendant and involved in base-pair interactions, with both Watson-Crick...Watson-Crick and Hoogsteen...Hoogsteen type pairings present. For the coordination polymers a rather unexpected influence of the tether length on the site of nucleobase binding is found for bridging ligand binding modes involving the chelating diamine and the adeninyl group. Polymer chains derived with the shorter ethyl tether show binding at the N7 site of adeninyl, while binding at N1 is found in the longer propyl chain length.

Tetranuclear coordination assemblies based on half-sandwich ruthenium(II) complexes: noncovalent binding to DNA and cytotoxicity.

The reaction of [(cymene)RuCl(2)](2) with K(2)Hoxonate (H(3)oxonic = 4,6-dihydroxy-2-carboxy-1,3,5-triazine acid) in methanol leads to the formation of the dinuclear half-sandwich ruthenium(II) complex [(cymene)(2)Ru(2)(mu-Hoxonato)Cl(2)] (1a). Removal of the chloride ligands of 1a by treatment with AgCF(3)SO(3) yields [(cymene)(2)Ru(2)(mu-Hoxonato)(CF(3)SO(3))(2)] (1b), which, upon posterior reaction with N,N'-linkers (L = 4,4'-bipyridine (4,4'-bpy), 4,7-phenantroline (4,7-phen)), gives rise to the formation of the tetranuclear open boxes [(cymene)(4)Ru(4)(mu-Hoxonato)(2)(mu-N,N'-L)(2)](CF(3)SO(3))(4) (2a, L = 4,4'-bpy; 2b, L = 4,7-phen). These systems have been characterized by (1)H NMR, UV-vis, and ESI-MS. The single-crystal structures of the dinuclear precursor 1a and of the clathrate 2b 4,7-phen have been determined. The interaction of these systems with cysteine, mononucleotides, and calf-thymus DNA has been studied by means of (1)H NMR, UV-vis, circular dicroism, competitive binding assays, and atomic force microscopy imaging. The results show that the robust tetracationic ruthenium(II) cyclic systems 2a and 2b do not give ligand exchange reactions toward biorelevant ligands. Nevertheless, these systems are able to noncovalently bind to DNA, probably at the surface of the major groove, inducing significant conformational changes in this biomolecule. It is also interesting to note that compounds 2a and 2b, in spite of only giving supramolecular interactions with biomolecules, exhibit antitumor activity, particularly toward the human ovarian cancer cell line A2780cisR, showing acquired resistance to cisplatin, with respective 4.6 and 8.3 microM IC(50) values.

Multifunctional behavior of molecules comprising stacked cytosine-AgI-cytosine base pairs; towards conducting and photoluminescence silver-DNA nanowires.

DNA molecules containing a 1D silver array may be applied for nanotechnology applications, but first their conducting and photoluminescence behavior must be enhanced. Here we have synthesized and characterized three new helical compounds based on stacked silver-mediated cytosine base pairs [Ag(mC)2]X (mC = N1-methylcytosine; X = NO3 (1), BF4 (2) and ClO4 (3)), that contain uninterrupted polymeric AgI chains that run through the center of the helixes, comparable to related silver-DNA structures. The exposure of nanostructures of [Ag(mC)2]BF4 (2) to cold hydrogen plasma stimulates the reduction of the prearranged AgI polymeric chains to metallic silver along the material. This solvent-free reduction strategy leads to the compound [AgI(mC)2]X@Ag0 (2H) that contains uniformly well-distributed silver metallic nanostructures that are responsible for the new conducting and photoluminescence properties of the material. The presence of silver nanostructures alongside compound 2H has been evaluated by means of X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, and X-ray powder diffraction (XRPD). The conducting and photoactive properties of 2H were studied by electrostatic force microscopy (EFM) and conducting-AFM (c-AFM), and photoluminescence microscopy (PL), respectively. The results demonstrate that the presence of well-organized metallic silver nanoentities on the material is responsible for the novel conductivity and photoactive properties of the material. This methodology can be employed for the generation of multifunctional silver-DNA related materials with tailored properties.

Electrochemically and photochemically active Palladium(II) heterotopic metallacalix[3]arenes.

The cyclic trinuclear system, [(en)(3)Pd(3)(4,7-phen)(3)](6+), undergoes a ligand exchange reaction with 5-R-2-hydroxypyrimidine derivatives (HRpymo; R = ethynylferrocene, 5-(dimethylamino)-N-(2-propynyl)-1-naphthalene sulfonamide) to give [(en)(3)Pd(3)(4,7-phen)(2)(Rpymo)](5+), functional supramolecular receptors of mononucleotides.

Cyclic tetranuclear half-sandwich ruthenium(II) complexes with 4,7-phenanthroline and hydroxo bridges: crystal structure, solution behaviour and binding to nucleosides.

The reaction between [(eta(6)-p-cymene)Ru(H2O)3]X2 and 4,7-phenanthroline (phen) leads to the formation of the rectangular tetranuclear complexes [(eta(6)-p-cymene)4Ru4(mu-4,7-phen-N4,N7)(2)(mu-OH)4]X4 (X=NO3, 1a; SO3CF3, 1b) which have been structurally characterised by X-ray crystallography. 1H NMR spectroscopic studies suggest the presence of a partially dissociated dinuclear species of type [(eta6-p-cymene)2Ru2(mu-4,7-phen-N4,N7)(solv)4]4+ in equilibrium with the tetranuclear cyclic species found in the solid state. The temperature effect for this equilibrium was studied by variable temperature 1H NMR experiments in D2O and MeOD. The results reveal that the proportion of the tetranuclear species increases with the polarity of the solvent which favour stacking interactions between the phenanthroline moieties. In addition, the reactivity of the tetranuclear species towards the nucleosides guanosine (Guo), cytidine (Cyt), 2'-deoxythymidine (Thy) and 2'-deoxyadenosine (dAdo) has been monitored by (1)H NMR as a potential model for the interaction of the 1 species with the probable DNA target. The results reveal that the 1 systems are able to bind the nucleobases endocyclic nitrogen atoms of Guo Cyt, and dAdo.

Cuba's Scientific Contributions to Global Polio Eradication.

Cuba eliminated polio in 1962 and was among the first countries to do so. Since then, only 20 cases of vaccine-derived paralytic poliomyelitis have been reported. Because Cuba used oral poliovirus vaccine exclusively in two mass campaigns usually in February and April each year, Sabin viruses were detected only within approximately 6-8 weeks after each annual campaign. This made Cuba a very attractive site to study the epidemiology of poliomyelitis in a tropical country without risk of secondary transmission of Sabin viruses for a large part of each year, an advantage over countries that used oral poliovirus vaccine continuously throughout the year in routine immunization programs. This report summarizes the unique scientific collaboration between Cuba's Ministry of Public Health and WHO, with participation by US scientists, in the global effort to eradicate polio. KEYWORDS Poliomyelitis, disease eradication, disease elimination, oral poliovirus vaccine, Sabin vaccine, inactivated poliovirus vaccine, Salk vaccine, Cuba, WHO.

Vaccine-related adverse events in Cuban children, 1999-2008.

INTRODUCTION Cuba has implemented an effective National Immunization Program since 1962. The schedule, administered primarily to children, comprises 11 vaccines (8 domestically produced) protecting against 13 diseases. In 1999 Cuba launched a national vaccine adverse event surveillance system to monitor and assess the safety of the immunization program, its vaccination procedures and the products administered. OBJECTIVES Describe adverse events following vaccination reported in children aged <16 years in Cuba from 1999 through 2008. METHODS A retrospective descriptive study was conducted of adverse events following vaccination reported from January 1999 through December 2008. Variables used: year, number of adverse events, province, type of vaccine, type and severity of adverse events (common minor, rare, severe), vaccination program errors, number of deaths, and final results of investigations of severe events. Percentages and rates per dose administered were calculated. Adverse event rates were calculated per 100,000 doses administered and by percentages of individual effects among events reported. RESULTS A total of 45,237,532 vaccine doses were administered, and 26,159 vaccine-associated adverse events were reported (overall rate: 57.8 per 100,000 doses). The group aged 0-5 years reported the highest rate of vaccine-associated adverse events (82/100,000 doses). The DTwP vaccine exhibited the highest rate of adverse events. Common minor events were: fever (17,538), reactions at injection site (4470) and systemic side effects (2422). Rare events (by WHO definition) reported were: persistent crying (2666), hypotonic-hyporesponsive episodes (3), encephalopathy (2) and febrile seizures (112). Severe events included: anaphylaxis (2), respiratory distress (1), multiple organ failure (1), sudden death (1), vaccine-associated paralytic poliomyelitis (2), toxic shock syndrome (3), and sepsis (1). The 10 deaths and 3 cases of disability were investigated by an expert commission, which concluded that 8 of the 13 severe events were vaccination-related. CONCLUSIONS Low rates of severe vaccine-associated adverse events observed in this study underline the low risk of vaccination relative to its demonstrated benefits in Cuba. Decision-making for the continued success of the National Immunization Program is supported by reliable information from comprehensive national surveillance with standarized reporting, along with multidisciplinary expert analysis of rare and severe adverse events and program errors. KEYWORDS Immunization; immunization programs; vaccines; vaccination; product surveillance, postmarketing; adverse drug event; communicable disease control; Cuba.

INTRODUCCIÓN Cuba tiene implementado un efectivo Programa Nacional de Inmunización desde 1962. El programa, dirigido principalmente a los niños, incluye 11 vacunas (8 de producción nacional) que protegen contra 13 enfermedades. En 1999, Cuba comenzó un programa de vigilancia de eventos adversos para monitorizar y evaluar la seguridad del programa de inmunización, los procedimientos de vacunación, y los productos utilizados. OBJETIVO Describir los eventos adversos asociados a la vacunación de niños de menos de 16 años, notifi cados en Cuba entre los años 1999­2008. MÉTODOS Se realizó un estudio descriptivo retrospectivo de los eventos adversos comunicados después de una vacunación, desde enero de 1999 hasta diciembre de 2008. Las variables utilizadas fueron: año, número de eventos adversos, provincia, tipo de vacuna, tipo y gravedad de los eventos adversos (leves y comunes, raros, severos), errores en el programa de vacunación, número de fallecidos y resultados fi nales de la investigación de los eventos severos. Se calcularon los porcentajes y las tasas por dosis aplicadas. Las tasas de eventos adversos se calcularon por 100,000 dosis aplicadas y según el porcentaje de efectos individuales entre los eventos comunicados. RESULTADOS Un total de 45,237,532 dosis de vacunas fueron administradas y se notifi caron 26 159 eventos adversos (tasa total: 57,8 por 100,000 dosis). La tasa más alta de eventos adversos asociados a la vacunación se identifi có en el grupo de 0­5 años (82/100,000 dosis). La vacuna DTPe (difteria, tétanos y pertusis de células enteras) mostró la tasa más alta de eventos adversos. Los eventos leves comunes fueron: fi ebre (17 538), reacciones en el sitio de inyección (4470) y efectos colaterales a nivel sistémico (2422). Los eventos raros comunicados (según defi nición de la OMS) fueron: llanto persistente (2666), episodios de hipotonía-hipo reactividad (3), encefalopatía (2) y convulsiones febriles (112). Los eventos graves incluyeron: anafi laxia (2), distrés respiratorio (1), síndrome de shock tóxico (3) y sepsis (1). Los 10 casos fallecidos y los 3 con incapacidad fueron investigados por una comisión de expertos, que concluyó que 8 de los 13 eventos severos estuvieron relacionados con la vacunación. CONCLUSIONES Las bajas tasas de eventos adversos graves asociados a la vacunación, observadas en este estudio, subrayan el bajo riesgo de la vacunación con respecto a sus benefi cios en Cuba. La toma de decisiones para mantener exitosamente el Programa Nacional de Inmunización se apoya en la información fi dedigna y en los informes estandarizados suministrados por el exhaustivo sistema de vigilancia nacional, conjuntamente con el análisis, por expertos multidisciplinarios, de los eventos adversos raros y severos y de los errores del programa. PALABRAS CLAVE Inmunización; programas de inmunización, vacunas, vacunación, sistema de vigilancia de productos, eventos adversos, control de enfermedades transmisibles, Cuba

Modification of DNA-templated conductive polymer nanowires via click chemistry.

DNA templated nanowires of a pentynyl-modified poly2-(2-thienyl)-pyrrole undergo functionalisation via"click chemistry" and retain their 1D-nanostructure and conductive properties.