Propriedades e funções

As melaninas contêm propriedades de grande interesse que estão relacionadas com várias funções desempenhadas, das quais se destacam a fotoprotecção e a pigmentação [Subianto

et al. 2005]. Devido à elevada capacidade de absorção da luz visível e eficiência no

isolamento de radicais livres [Reszka et al. 1998], estes antioxidantes possuem uma função fotoprotectora. Uma das propriedades mais surpreendentes das melaninas é o facto de absorverem em toda a gama ultravioleta-visível [Panzella et al. 2007, Albuquerque et al. 2006] enquanto as restantes biomoléculas apresentam picos bem definidos na zona dos 280 nm [Powell 2005]. Paradoxalmente apresentam uma função fotoprotectora, mas também estão relacionadas com a formação de melanomas [Zang et al. 2000, Napolitano et al. 1996, Di e Bi 2003].

Como pigmento, as melaninas são responsáveis pela padronização das cores nos cabelos, olhos, pele e plumagem de numerosos vertebrados [Tran et al. 2006, Albuquerque et al. 2006, Schweikardt et al. 2007]. Esta pigmentação pode ser de grande importância na selecção natural e sexual [Bókony et al. 2003, MacGraw e Hill 2000].

A presença da melanina na substantia nigra do cérebro e em outras áreas não expostas às radiações solares, como o ouvido interno, sugere outras funções [Albuquerque et al. 2006, Galvão e Caldas 1989]. Uma dessas funções é a de absorção do som, que está directamente relacionado com o enorme acoplamento electrão-fotão deste biomaterial [Kono et al. 1979]. Recentemente foi proposto que a melanina desempenha uma função mais ligada à resposta imunitária do que à fotoprotecção [Burkhart e Burkhart 2005, Wilms et al. 2007, Rosas et

al. 2000]. Contudo, é sabido que a eumelanina e a feomelanina estão relacionados com o

desenvolvimento do cancro da pele e que a ausência de neuromelanina (híbrido entre a eumelanina e a feomelanina), no cérebro, está na origem de várias doenças neurodegenerativas, como por exemplo, a doença de Parkison [Tei et al. 1998, Pedrosa e Soares-da-Silva 2002, Dzierzega-Lecznar et al. 2004, Meredith et al. 2006].

1.5.3 Estrutura

De um modo geral, a estrutura da eumelanina é aceite como sendo constituída por unidades monoméricas de várias formas redox do ácido 5,6-dihidroxindolo-2-carboxílico (DHICA) e/ou 5,6-dihidroxindolo (DHI), com possíveis locais de polimerização representados na figura 1.49 [Tran et al. 2006, Powell 2005, Meredith et al. 2005, Liu e Simon 2003].

Figura 1.49 – Estruturas de DHI (5,6-dihidroxindolo) e DHICA (ácido 5,6-dihidroxindolo-

2-carboxílico) [Tran et al. 2006, Powell 2005].

Nessas formas redox estão incluídas as semi-quinonas (SQ), as indoloquinonas (IQ) e imina-quinonas (QI). Estes monómeros ligam-se uns aos outros, supostamente, de uma forma aleatória, para formar oligómeros e polímeros. As moléculas monoméricas podem estar em vários estados de oxidação, como é possível visualizar na figura 1.50 [Meredith et

al. 2006]. Desta forma, é possível verificar que a melanina não é uma molécula

convencional e bem definida, mas sim uma mistura heterogénea destas unidades estruturais básicas ligadas aleatoriamente [Tran et al. 2006, Powell 2005].

Nos sistemas vivos, as melaninas podem estar ligadas a outras moléculas tais como proteínas que podem, afectar as propriedades destes pigmentos, nomeadamente a sua solubilidade [Liu e Simon 2003, Meredith et al. 2006, Capozzi et al. 2006].

Figura 1.50 – Estrutura do DHI (5,6-dihidroxindolo), e suas formas oxidadas SQ (forma

reduzida da semiquinona), IQ (indoloquinona) e QI (quinona-imina), e o DHICA (ácido 5,6-dihidroxindolo-2-carboxílico): estruturas monoméricas da eumelanina. Formas isoméricas, tautoméricas e redox dos intervenientes na formação da melanina [Meredith et

Contudo, a grande dúvida a nível estrutural global das melaninas é se estes oligómeros formam heteropolímeros extensos como os que estão representados na figura 1.51 [Mason e Raper] ou se nanoagregados, como reproduzido na figura 1.52 [Capozzi et al. 2006, Clancy

et al. 2000, Powell 2005, Galla et al. 2000, Stark et al. 2005].

Figura 1.51 – Exemplo de estrutura química de melanina natural [Barnes 1988].

No esquema dos nanoagregados é proposto que cinco a dez unidades monoméricas ligam- se dando origem a um pequeno oligómeros planar, a protomolécula. Estes oligómeros por sua vez condensam-se através de ligações π, dando origem aos nanoagregados com duas ou três camadas. Estes nanoagregados podem juntar-se em cluster através de interacções do tipo pontes de hidrogénio, como está ilustrado na figura 1.52 [Clancy e Simon 2001, Powell 2005, Stark et al. 2005, Tran et al. 2006].

Figura 1.52 – Estruturas possíveis para 3 tipos de hexámeros da melanina: oxidada (a),

semi-reduzida (b) e reduzida (c), onde as ligações de hidrogénio estão representadas a tracejado azul [Stark et al. 2005].

Desta forma, quanto mais reduzidas forem as estruturas maior a probabilidade para as ligações de hidrogénio, intra e inter-camadas, e consequente variação dos espectros de absorção. Portanto, nas estruturas mais oxidadas as interacções serão apenas intra-camadas, havendo menor possibilidade de formação de camadas múltiplas [Tran et al. 2005]. O modelos dos nanoagregados foi baseado em estudos de raio-X WAXS (do inglês Wide- Angle X-Ray) ou SAXS (do inglês Small-Angle X-Ray) e microscopia de força atómica (AFM – do inglês Atomic Force Microscopy) [Tran et al. 2006, Stark et al. 2005, Dezidério

et al. 2004, Clancy e Simon. 2001]. Alguns estudos demonstraram que também podem

formar-se filamentos. Uma explicação possível para estas estruturas está ilustrada na figura 1.53 [Clancy e Simon 2001].

Figura 1.53 – Estrutura esquemática da eumelanina. A unidade estrutural básica do

oligómero planar é constituído por aproximadamente 5 unidades de DHICA/DHI. Estas unidades oligoméricas estão ligadas entre si através de interacções π, que formam, por sua vez, os filamentos [Clancy e Simon 2001].

A ideia da biomolécula com uma estrutural baseada na heterogeneidade ou na desordem apresenta uma grande ruptura na doutrina bioquímica, onde todas as moléculas possuem uma estrutura muito bem definida [Stark et al. 2005, Liu e Simon 2003]. É esta desordem que faz com que as aproximações feitas por análise espectroscópica e difracção de raio-x, técnicas usadas com grande sucesso na elucidação de estruturas de outras biomacromoléculas complexas, sejam tão ineficientes no estudos das melaninas [Liu e Simon 2003]. Contudo, é também esta desordem estrutural que dá à melanina a capacidade de ter muitas propriedades de grande interesse [Galvão e Caldas 1989, Albuquerque et al. 2006, Liu e Simon 2003, Tran et al. 2006, Capozzi et al. 2006, Powell 2005, Gallas et al. 2000].

Cálculos utilizando a teoria da minimização da energia funcional e simulação molecular dinâmica [Stark et al. 2005] sugerem que a larga banda de absorção da melanina pode ser atribuída ao enorme aglomerado de diferentes monómeros e oligómeros, cada um com um pico ligeiramente diferente. A figura 1.54 mostra os espectros de absorção de uma folha hexamérica, em vários estados de oxidação. A aglomeração das folhas e outros factores também podem alterar e forma dos picos. Foi, assim, proposto que com toda esta desordem, a sobreposição dos picos individuais daria origem a um largo e monotónico espectro de absorção, como é observado experimentalmente [Stark et al. 2005].

A

B

Figura 1.54 – A) Espectro de absorção calculado para um hexamero de camada única,

oxidado (preto), semi-reduzido (vermelho) e reduzido (azul). B) Bandas de absorção calculadas para hexameros sintéticos da melanina. O espectro da estrutura mais oxidada, com apenas 1 camada está representado a azul, a vermelho está delineado o espectro de absorção da dupla camada e a verde o da tripla camada [Stark et al. 2005].

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