<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0034-7418</journal-id>
<journal-title><![CDATA[Revista Colombiana de Ciencias Químico - Farmacéuticas]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. colomb. cienc. quim. farm.]]></abbrev-journal-title>
<issn>0034-7418</issn>
<publisher>
<publisher-name><![CDATA[Departamento de Farmácia, Facultad de Ciencias, Universidade Nacional da Colombia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0034-74182020000300602</article-id>
<article-id pub-id-type="doi">10.15446/rcciquifa.v49n3.91249</article-id>
<title-group>
<article-title xml:lang="pt"><![CDATA[Funcionalização do polietilenoglicol metil éter via reação de bromoacetilação: ativação, caracterização por MALDI-TOF e mecanismo de reação]]></article-title>
<article-title xml:lang="en"><![CDATA[Poly(ethylene glycol) methyl ether functionalization by bromoacetylation reaction: Activation, characterization by MALDI-TOF and reaction mechanism]]></article-title>
<article-title xml:lang="es"><![CDATA[Funcionalización de polietilenglicol metil éter mediante reacción de bromoacetilación: activación, caracterización por MALDI-TOF y mecanismo de reacción]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pereira B. Cordeiro]]></surname>
<given-names><![CDATA[Lídia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Lima]]></surname>
<given-names><![CDATA[William Gustavo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Soares]]></surname>
<given-names><![CDATA[Ana Caroline]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Borges]]></surname>
<given-names><![CDATA[Marcia Helena]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[de Lima]]></surname>
<given-names><![CDATA[Maria Elena]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Moreira Brito]]></surname>
<given-names><![CDATA[Júlio César]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidade Federal de Minas Gerais  ]]></institution>
<addr-line><![CDATA[Belo Horizonte MG]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Fundação Ezequiel Dias  ]]></institution>
<addr-line><![CDATA[Belo Horizonte MG]]></addr-line>
<country>Brasil</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Instituto de Ensino e Pesquisa  ]]></institution>
<addr-line><![CDATA[Santa Casa-Belo Horizonte MG]]></addr-line>
<country>Brazil</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2020</year>
</pub-date>
<volume>49</volume>
<numero>3</numero>
<fpage>602</fpage>
<lpage>613</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0034-74182020000300602&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0034-74182020000300602&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0034-74182020000300602&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo A PEGuilação, reação química de conjugação com a molécula de polietilenoglicol (PEG) ou polietilenoglicol metil éter (mPEG), tem sido amplamente aplicada pelas indústrias farmacêuticas como estratégia de melhoria das propriedades farmaco-cinéticas de compostos bioativos. O PEG é um polímero que possui um esqueleto de poliéter quimicamente inerte e que apresenta grupos hidroxilas (-OH) em suas extremidades. Assim, o PEG para tornar-se apto como reagente de conjugação deve ser ativado com um grupo funcional que seja reativo. Nesse sentido, a bromoaceti-lação apresenta-se como uma alternativa para a funcionalização do PEG. Portanto, nesse trabalho objetivamos descrever em detalhes os procedimentos e o mecanismo de reação envolvida na funcionalização do mPEG, através da reação de bromoacetilação. Além do mais, estudamos a aplicação do MALDI-ToF para a caracterização do produto ativado. Após a bromoacetilação, por um procedimento adaptado, obteve-se o bromoacetil-mPEG-éster, com rendimento bruto de 56,78%. Análises posteriores, por espectrometria de massas por MALDI-ToF, possibilitaram identificar e caracterizar o produto bromoacetilado. Entre as condições de reação, o controle de temperatura (-10 °C a 0 °C) mostrou-se eficaz favorecendo a adição nucleofílica essencial à bromoacetilação. Assim, concluímos que o controle da baixa temperatura reacional é um fator chave para o favorecimento da adição nucleofílica à carbonila e, portanto, essencial na obtenção do mPEG funcionalizado via bromoacetilação. Estudos posteriores serão necessários, no entanto, para confirmar se o mPEG esterificado, nessas condições, poderá ser utilizado na conjugação com moléculas de natureza proteica ou peptídica, por meio de substituição nucleofílica bimolecular.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[SUMMARY PEGylation, a chemical reaction of conjugation with the polyethylene glycol molecule (PEG), has been widely applied by the pharmaceutical industries as a strategy to improve the pharmacokinetic properties of bioactive compounds. PEG is a polymer that has a chemically inert polyether backbone and hydroxyl groups (-OH) at its ends. Thus, PEG to become fit as a reagent for conjugation must be activated with a functional group that is reactive. In this sense, bromoacetylation presents itself as an alternative for the functionalization of PEG. Therefore, in this study we aim to describe in detail the procedures and reaction mechanism involved in the functionalization of mPEG through the bromoacetylation reaction. In addition, we used the spectrometric technique, by MALDI-ToF, for the characterization of the activated product. After applying an adapted bromoacetylation procedure, bromoacetyl-mPEG-ester was obtained with a yield of 56.78%. Subsequent analyzes of MALDI-ToF mass spectrometry were able to correctly identify and characterize the bromoacety-lated product. Among the reaction conditions, temperature control (from -10 °C to 0 °C) was effective in favoring the essential nucleophilic addition to bromoacetylation. Thus, we conclude that the control of the low reaction temperature is a key factor in favoring the nucleophilic addition to carbonyl and, therefore, obtaining a favorable conversion to functionalized PEG via bromoacetylation. Further studies, however, will be necessary to confirm whether PEG esterified with these conditions can be used in conjunction with molecules of a protein or peptide nature by means of bimolecular nucleophilic substitution.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN La PEGilación, una reacción química de conjugación con la molécula de polietilenglicol (PEG), ha sido ampliamente aplicada por las industrias farmacéuticas como una estrategia para mejorar las propiedades farmacocinéticas de los compuestos bioactivos. El PEG es un polímero formado por un esqueleto de poliéter químicamente inerte con grupos hidroxilo (-OH) en sus extremos. Por lo tanto, para usar el PEG como reactivo de conjugación debe activarse con un grupo funcional que sea reactivo. En este sentido, la bromoacetilación es una alternativa para la funcionalización de PEG. De esta manera, en este trabajo nuestro objetivo es describir en detalle los procedimientos y el mecanismo de reacción involucrados en la funcionalización de PEG a través de la reacción de bromoacetilación. Además, estudiamos la aplicación de MALDI-ToF para la caracterización del producto activado. Después de aplicar un procedimiento de bromoacetilación adaptado, se obtuvo bromoacetil-mPEG-éster con un rendimiento bruto de 56,78%. Los análisis posteriores de espectrometría de masas por MALDI-ToF pudieron identificar y caracterizar correctamente el producto bromoacetilado. Entre las condiciones de reacción, el control de la temperatura (desde -10 °C hasta 0 °C) fue eficaz para favorecer la adición nucleofílica esencial a la bromoacetilación. Así, concluimos que el control de la baja temperatura de reacción es un factor clave para favorecer la adición nucleofílica al carbonilo y, por lo tanto, esencial para obtener el mPEG funcionalizado mediante la bromoacetilación. Sin embargo, serán necesarios más estudios para confirmar si el mPEG esterificado en estas condiciones puede usarse junto con moléculas de naturaleza proteica o peptídica por medio de la sustitución nucleófila bimolecular.]]></p></abstract>
<kwd-group>
<kwd lng="pt"><![CDATA[Polietilenoglicol (PEG)]]></kwd>
<kwd lng="pt"><![CDATA[PEGuilação]]></kwd>
<kwd lng="pt"><![CDATA[bromoacetilação]]></kwd>
<kwd lng="pt"><![CDATA[adição nucleofílica]]></kwd>
<kwd lng="en"><![CDATA[polyethylene glycol (PEG)]]></kwd>
<kwd lng="en"><![CDATA[PEGylation]]></kwd>
<kwd lng="en"><![CDATA[bromoacetylation]]></kwd>
<kwd lng="en"><![CDATA[nucleophilic addition]]></kwd>
<kwd lng="es"><![CDATA[Polietilenglicol (PEG)]]></kwd>
<kwd lng="es"><![CDATA[pegilación]]></kwd>
<kwd lng="es"><![CDATA[bromoacetilación]]></kwd>
<kwd lng="es"><![CDATA[adición nucleofílica]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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