BIOINORGÂNICA

2006 / 2007

Bioinorganic chemistry (wikipedia)

Bioinorganic chemistry is a specialized field that spans the chemistry of metal-containing

molecules within biological systems. This field is concerned with the control and use of metal

ions in biochemical processes. Although bioinorganic chemistry includes the study of

artificially introduced metals (e.g. medicinally), many natural occurring biological processes

(such as respiration) depend upon molecules containing inorganic elements, such as

metalloproteins, and these natural processes are also studied by bioinorganic chemistry.

Bioinorganic chemistry has developed from the continuing research in inorganic chemistry

and its important associations in biological chemistry.

As a mix of biochemistry and inorganic chemistry, bioinorganic chemistry is important in

realizing the implications of electron-transfer proteins, substrate bindings and activation, atom

and group transfer chemistry as well as metal properties in biological chemistry.

History

Paul Ehrlich used organoarsenic (“arsenicals”) for the treatment of syphilis, demonstrating the relevance of metals, or at least metalloids, to medicine, that blossomed with Rosenberg’s discovery of the anti-cancer activity of “cisplatin (cis-PtCl2(NH3)2).

The first protein ever crystallized (see James B. Sumner) was urease, which was later shown to contain nickel at its active site. Vitamin B12, the cure for pernicious anemia was shown crystallographically by Dorothy Crowfoot Hodgkin to consist of a cobalt in a corrin macrocycle.

The Watson-Crick structure for DNA demonstrated the key structural role played by phosphate-containing polymers.

Research areas

Metal ion transport and storage covers a diverse collection of ion channels, ion pumps (e.g. NaKATPase), vacuoles, siderophores, and other proteins and small molecules whose aim is to carefully control the concentration of metal ions in the cell.

Hydrolase enzymes include a diverse collection of proteins that interact with water and substrates. Examples of this class of metalloproteins are carbonic anhydrase, metallophosphatases, and metalloproteinases.

Metal-containing electron transfer proteins are comprised of three major classes:iron-sulfur proteins such as rubredoxins, ferredoxins, Rieske proteins, and aconitases blue copper proteinscytochromes

These electron transport proteins are complementary to the non-metal electron transporters nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD).

Oxygen transport and activation proteins make extensive use of metals such as iron, copper, and manganese. Heme is utilized by red blood cells in the form of hemoglobin for oxygen transport and is perhaps the most recognized metal system in biology. Other oxygen transport systems include myoglobin, hemocyanin, and hemerythrin. Oxidases and oxygenases are metal systems found throughout nature that take advantage of oxygen to carry out important reactions such as energy generation in cytochrome c oxidase or small molecule oxidation in cytochrome P450 oxidases or methane monooxygenase. Some metalloproteins are designed to protect a biological system from the potentially harmful effects of oxygen and other reactive oxygen-containing molecules such as hydrogen peroxide. These systems include peroxidases, catalases, and superoxide dismutases. A complementary metalloprotein to those that react with oxygen is the oxygen evolving complexpresent in plants. This system is part of the complex protein machinery that produces oxygenas plants respire.

Bioorganometallic systems such as hydrogenases and methylcobalamin are biological examples of organometallic chemistry.

The nitrogen metabolism pathways make extensive use of metals. Nitrogenase is one of the more famous metalloproteins associated with nitrogen metabolism.

More recently, the cardiovascular and nueronal importance of nitric oxide has been examined, including the enzyme nitric oxide synthase. (See also: nitrogen assimilation.)

The purpose of Bioinorganic Chemistry and Applications is to publish original research in the form of articles, notes, letters and reviews in the general field of bioinorganic chemistry and its applications. Its scope includes all aspects of bioinorganic chemistry, including bioorganometallic chemistry and applied bioinorganic chemistry. The journal welcomes papers relating to metalloenzymes and model compounds, metal-based drugs, biomaterials, biocatalysis and bioelectronics, metals in biology and medicine, metals toxicology and metals in the environment, metal interactions with biomolecules and spectroscopic applications.

http://www.chem.qmul.ac.uk/iupac/bioinorg/(IUPAC Recommendations 1997)

The definitions used in this glossary are identical to those in the published document, see M.W.G. de Bolster, Pure Appl. Chem., 69, 1251-1303 (1997) [Copyright IUPAC; reproduced with the permission of IUPAC]. If you use any of these definitions please cite this reference as their source. Any changes have been marked by which is a link to details of the change and where it applies.

For problems in converting the text into a World Wide Web version see the IUPAChome page.

As well as an introduction and index. All terms are listed alphabetically in the following files: A and B; C and D; E to G; H to L; M to O; P to R and S to Z.

GLOSSARY OF TERMS USED IN BIOINORGANIC CHEMISTRY(IUPAC Recommendations 1997)

A and BContinued from full contents.

Contents

Absolute configuration, Abzyme, Achiral, Acid, Acidity constant, Acid-labile sulfide, Aconitase, Active center, Active site, Adenosine 5'-triphosphate, Adrenodoxin, Aerobe, Albumin, Allosteric effector , Allosteric enzyme, Alpha() helix, Ambidentate, Amicyanin, Amino-acid residue, Anabolism, Anemia, Anaerobe, Anation, Anisotropy, Anti, Antibody, Antiferromagnetic, Antigen, Apoprotein, Aquation, Archaea, Assimilation, Assimilative, Assimilator, Asymmetric synthesis, Asymmetry parameter, ATP, Auranofin, Autotrophic organisms, Auxotroph, Azurin, Bacteriochlorin, Bacteriochlorophyll, Base, Base pairing, Basicity constant, Beta() sheet, Beta() strand, Beta() turn, Bifunctional ligand, Binding constant, Binding site, Binuclear, Bioassay, Bioavailability, Biocatalyst, Bioconjugate, Bioconversion, Bioleaching, Biological half life, Biomass, Biomembrane, Biomimetic, Biomineralization, Biopolymers, Biosensor, Biotransformation, Bleomycin, BLM , Blotting, Blue copper protein, Bone imaging , Brain imaging, Bridging ligand, Brønstedacid, Brønsted base

C and DContinued from terms starting with A and B

Contents

Cage, Calmodulin, Calpain, Carbonic anhydrase, Carbon monoxide dehydrogenases, Carboplatin, Cardiotech, Catabolism, Catalase, Catalytic antibody, CBS, CD, Central atom, Ceruloplasmin, Charge-transfer complex, Charge-transfer transition, Chaperonin, Chelation, Chelation therapy, Chemical shift, Chirality, Chlorin, Chlorophyll, Chloroplast, Chromophore, Circular dichroism, cis, Cisplatin, Clone, Cluster, Cobalamin, Codon, Coenzyme, Cofactor, Colloidal bismuth subcitrate, Comproportionation, Concanavalin A, Configuration, Conformation, Consensus sequence, Contrast agent, Cooperativity, Coordination, Corphin, Corrin, Crystal field, C-terminal amino-acid residue, Curie relation, Cytochrome, Cytochrome-c oxidase, Cytochrome P-450, Cytoplasm, Dehydrogenase, Denitrification, De-nol, Denticity, Deoxyribonucleic acid, Desferal, Desferrioxamine, dfo, Diamagnetic, Diastereoisomers, Dihydrofolate , Dinuclear, Dioxygenase, Dismutase, Dismutation, Disproportionation, Dissimilatory, Dissociation constant., DNA , Domain, Donor atom symbol, Double helix.

QUÍMICA BIOINORGÂNICA

Disciplina na interface ...

Complementaridade Impacto

Química Síntese e Catálise

Física Biologia

Bioquímica Medicina / Saúde

(Micro)Biologia Ambiente

Biologia Molecular Biotecnologia

CarbonoHidrogénio OxigénioAzoto

SódioMagnésiopotássioCálcio FósforoEnxofreCloro

ELEMENTOS QUÍMICOS E A VIDA

HidrogénioOxigénio

70% corpo humano

H2O

16 elementos(metais de transição)vestigiáriosessenciaisFe, Mo, Ni, Cu, Zn, Co

99 %0.7 %

He

Li Be B Ne

Al Ar

Sc Ti Cr Ga Ge As Br Kr

Rb Sr Y Zr Nb Ru Rh Pd Ag Cd In Sb Te Xe

Cs Ba La Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi

La Ce Pr Nd Sm Eu Gd Tb Dy Ho Er Tm Yb Lu

C

Pt Au

CrV

Ca Se

Li

99mTc

FeMg

Cu

Gd

I

F

Zn

Ag

Al

67Ga

B

N2O

N O

S

Ba

Na

K

Periodic Table of MedicinesPeriodic Table of Medicines

P

SbBi

Mn

Mo

CoSi

SrSn

Ti

133Xe201Tl

As90Y

188Re

153SmCs

La

SedoneuralBr

Cl

Peter Sadler

O meio ambiente condicionador da química da vidaO ambiente e a Vida - Condições limitantes

meio exterior meio interior

Parametro Limite inferior Limite superior

Temperatura -18 C (fungos, bactérias) +104 C (bactérias)

potencial oxidação-redução - 450 mV (bactérias) +850 mV (bactérias)

pH Próximo de 0 (Thiobacillus) 13 (bactérias

Pressão Próximo de zero (bactérias) 1400 atm (fossas abissais)

Salimidade água bidestilada (b. heterotróficas) Salmoura (b. halófilas)

Actividade da água 0.65-0.75 (Aspergillus) Aprox. 1

Abundância

Disponibilidade

Captura selectiva e concentração

A selecA selecçção dos elementos quão dos elementos quíímicos micos pelos sistemas biolpelos sistemas biolóógicosgicos

ELEMENTOS QUÍMICOS DA VIDA

SELECÇÃO DOS ELEMENTOS QUÍMICOS

FUNÇÕES QUÍMICAS DOS ELEMENTOS EM SISTEMAS BIO

ABUNDÂNCIA CÓSMICA DOS ELEMENTOS

Universo Terra Água do Mar Corpo Humano

H 91 O 47 H 66 H 63 He 9.1 Si 28 O 33 O 25.5 O 0.057 Al 7.9 Cl 0.33 C 9.5 N 0.042 Fe 4.5 Na 0.28 N 1.4 C 0.021 Ca 3.5 Mg 0.033 Ca 0.31 Si 0.003 Na 2.5 S 0.017 P 0.22 Na 0.003 K 2.5 Ca 0.006 Cl 0.03 Mg 0.002 Mg 2.2 K 0.006 K 0.06 Fe 0.002 Ti 0.46 C 0.0014 S 0.05 S 0.001 H 0.22 Br 0.0005 Na 0.03 C 0.19 Mg 0.01

Comparação de Análises Elementares - Universo, Terra, Água do Mar e Corpo Humano(em % do número total de átomos)

Abundância dos elementos químicos

catiões aniões neutros

H3O+, NH4+ HCO3

-, CO32-, NO3

- B(OH)3 Na+, K+ H2PO4

-, HPO42- CO2, SiO2

Mg2+, Ca2+ OH-, F-, Cl-, Br-, I-, SO42- N2, NH3, O2

metal espécies químicas principais

Al3+ Al(OH)3 Cr3+ Cr(OH)2+ CrO2

- Mn2+ MnCl+ MnSO4 Fe2+ Fe(OH)+ FeCl- Fe3+ Fe(OH)3 Fe(OH)2

+ Co2+ CoCl+ CoCO3 CoSO4 Ni2+ NiCl+ NiCO3 NiSO4 Cu2+ Cu(OH)Cl CuCO3 CuCl- Cu(OH)+ Zn2+ ZnCl+ ZnCl2 Zn(OH)Cl Mo6+ MoO4

2- Ag+ AgCl42- AgCl32- AgCl2- Cd2+ CdCl2 CdCl+ CdCl32- Hg2+ HgCl4- HgCl3Br2- HgICl3- Pb2+ PbCl2 PbCl- Pb(OH)+ (Pb(OH)Cl

Disponibilidade

Formas nas quais os principais elementos biológicos ocorrem em meio aquoso

CARBONO versus SILÍCIOVersatilidade / disponibilidade

CO2 solúvel na água (SiO2)

C – C C = C C ≡ C

Si-Si Si-O-Si-O-Si “insolubilidade”

_________________________________________Energias de ligação Kcal / mole_________________________________________

C – C 83C = C 143C ≡ C 200Si-Si 42Si-O 88

DiatomáciasA Silica como bloco construtor

elemento Conc. água do marppm

Concentração emorganismos marinhosppm

vanádio 2.5 280 000

ferro 2 86 000

molibdénio 10 6 400

Concentração e Captura selectiva (certos elementos químicos)

CO2 H2O N2

blocos construtores (ex. AAs)macromoléculasunidades supramolecularesorganeloscélulas tecidos organismos

monómeros

degradação

polímerosInstruçãoPlanoDNA

precursores

fotossíntese

matérias primasH, C, O, N, S, P

Na, K, Ca ...Fe, Co, Ni ...

O2

H2Orespiração

BIO-SISTEMAS ... do simples ao complexo ...

Experiência deMiller

... do simples ao complexo ...

Funções electroquímicas

Funções estruturais e suporte

Funções catalíticas

Enzimas activadas por metaisMetaloenzimas

i) catálise de reacções ácido-base (ácidos de Lewis): zinco e níquel

ii) catálise de reacções de oxidação-redução (transferência de electrões)

Cu(II)/Cu(I), Fe(IV)/Fe(III)/Fe(II), Mo(VI)/Mo(V)/Mo(IV), Ni(III)/Ni(II)

FunFunçções Principais dos Elementos Quões Principais dos Elementos Quíímicos micos de Interesse Biolde Interesse Biolóógicogico

CLASSIFICAÇÃO DOSCATIÕES EM SISTEMAS BIOLÓLOGICOS

sem permutacomplexos fortes

complexosfortes

ligandoscontendoN, S

estáticocatáliseredox

Fe (4+, 3+, 2+)Cu (2+, 1+)Co (3+, 2+)Mo (W) (+6, +5, +4)Ni (+3, +2)

sem permutacomplexos fortes

complexos fortes

ligandoscontendoN, S

estáticocatáliseZn (2+)Ni (2+)

permuta moderadamente rápida

complexos moderadamente fortes

ligação a aniões de oxigénio

semi-móvelformadores de estruturas

Mg (2+)Ca (2+)

permuta rápidacomplexos fracosligação a aniões de oxigénio

móveltransportadores de carga

Na (1+)K (1+)

Oxi-hemoglobina – oxigénio na sexta posição e coordenação, Fe(II) no plano do hemoDesoxi-hemoglobina - sexta posição de coordenação livre , Fe(II) fora do plano do hemoMet-hemoglobina – Fe(III) , com alteração da quinta posição de coordenação (His por Tir) Hemoglobina ligada a NO e Nitrito – estes ligandos ocupam a sexta posição axial

Conceito: RESPIRAÇÃO ... como obter energia .....

O2 é soluvel em águaO2 e H2 combinam-se na forma de águaO2 é um aceitador de electrões

O2

Substratos energéticos → e- e- e- → ↓H2 O

Respiração no sentido lato

SO4= → S=

H+ → H2

N2 → NH3

CO2 + H2 → CH4

CICLOS DOSELEMENTOS

DISSIMILAÇÃO ("Respiração")

ASSIMILAÇÃO

CICLO BIOLCICLO BIOLÓÓGICO do ENXOFREGICO do ENXOFRE

SO42-

So

R-SH S2-

compostos orgânicosreduzidos

1

43 7

5

6

8 2

1 - assimilação2 - dissimilação3 - oxidação quim e foto4 - oxidação de tiois5 - assimilação6 - degradação7 - dissimilação8 - oxidação

3