ReviewThe concept of photochemical enzyme models – State of the art
Introduction
Without enzymes, life as we know it would certainly be impossible. Only a few specific reactions are occurring non-enzymatically inside the cell [1]. On the other hand, a remarkably small number of different catalysts is responsible for accelerating the complex chemistry of all living organisms including humans in a perfect way [2], [3]. Already in the pioneering years of enzymology, researchers were therefore fascinated by the smooth and efficient performance of biocatalytic substrate conversions and started to compare them with other chemical processes [4], [5], [6], [7]. In a visionary lecture held more than hundred years ago, Nobel prize laureate Emil Fischer encouraged scientists to start creating man-made enzyme counterparts [8]:
“The chemical exploration of ferments is still at the very beginning […] even today I consider attempts to prepare them [… ]in an artificial way as a not too daring enterprise” (E. Fischer, 1907).
Since then, many different approaches have been followed to exploit the biological principles of enzymatic catalysis for abiotic and biomimetic chemical transformations. New methods have been developed which allowed to obtain the first purely synthetic enzymes with full biological activity [9]. The native protein scaffolds of biocatalysts have soon been modified and re-designed by genetic engineering [10]. De-novo design of polypeptide structures not directly related to any sequence found in nature also emerged as a powerful tool to control the function of the protein matrix [11]. One of the fascinating more recent goals is to incorporate amino acids not included in the standard genetic code into synthetic polypeptides for improving enzymatic catalysis [12], [13]. Another possibility to create non-natural variants of biocatalysts is the reconstitution of native or engineered apo-proteins with modified organic coenzymes or synthetic metal-based cofactors [14], [15], [16], [17], [18]. Progress and trends in artificial protein design and synthetic biology [19] have recently been summarized elsewhere in more detail [20], [21], [22].
Low-molecular-weight catalysts which display an enzyme-like reactivity in the absence of a protein matrix in contrast are much harder to devise. If successful, this alternative approach may significantly broaden the range of technological applications of enzymatic catalysis by eliminating certain practical drawbacks of protein-based systems such as stability problems under non-physiological conditions or the sometimes quite narrow substrate scope. Therefore, tremendous efforts have been made in organic, supramolecular and bioinorganic chemistry to develop artificial enzymes or synthetic model enzymes from scratch based on robust molecular components [23], [24], [25]. A typical case of such a stable low-molecular weight non-peptidyl enzyme mimic is illustrated in Fig. 1.
Despite of the increasing interest in small biomimetic and bio-inspired catalysts, however, only very few examples of artificial enzyme substitutes with efficiencies and selectivities rivaling those of natural systems have been reported up to now [25], [28]. This is due to the fact that in the majority of cases the structure and dynamics of the protein matrix surrounding a catalytic center play a crucial role for the correct function of an enzymatic reaction mechanism and thus cannot be neglected. Therefore, many active site analogs both structurally and spectroscopically representing a perfect copy of a specific substrate binding site may still remain catalytically inactive. On the other hand, synthetic counterparts replacing the highly reactive key-intermediates temporarily formed in the catalytic cycles of enzymatic processes will of course hardly be obtained and isolated as robust and stable model compounds.
To overcome these serious problems, more flexible design strategies for the creation of artificial enzymes have to be considered. In this context, the novel concept of photochemical enzyme models (artificial photoenzymes) was introduced [29], [30], [31], [32]. By exploiting the excited-state properties and dynamics of robust low-molecular weight catalyst precursors to impose light-controlled electronic, energetic and structural changes at a substrate binding site, the selective and efficient chemistry of biocatalysts can be readily replaced. This new strategy allows to create competitive functional enzyme models based on small molecular systems in the absence of a dynamic protein environment. Some recent progress in this currently emerging field [28], [33], [34], [35] of biomimetic and bio-inspired photocatalysis with light-driven enzyme models is summarized in the present review.
Section snippets
Design principles, benefits and assesment criteria
Photons at the same time transport a quantum of energy and a bit of information [33]. Both aspects can be systematically exploited to develop functional model systems mimicking the performance of natural systems. Excited-state compounds are selectively activated species with their own characteristic physical and chemical properties thus providing a completely new dimension for the design of molecular devices and functional materials [36]. Many useful reaction intermediates not accessible
Artificial photoenzymes in green chemistry and synthesis
Following the principles of green chemistry for manufacturing valuable compounds in an economical, resource-preserving and environmentally benign way has been identified as a crucial roadmap for the survival of mankind [44], [45]. Especially in combination with long-wavelength solar radiation as a source of renewable energy such a strategy could offer interesting new perspectives for a sustainable chemistry of the future. Light is a clean and highly selective reagent that can be readily
Artificial photoenzymes for energy conversion and storage
While the synthetic applications of biomimetic photocatalysis described above are typically restricted to the acceleration of energetically downhill reactions, the concept of artificial photoenzymes also offers a straightforward route to achieve direct chemical storage of light energy. Many different energy-rich products (solar fuels) may be targeted in artificial photosynthetic devices based on molecular catalyst systems with an enzyme-like reactivity. The state of the art of this important
Artificial photoenzymes in medicine and life sciences
Beneficial and destructive effects of light exposure on living organisms have been observed since ancient times. Systematic applications of sensitizing compounds in photodynamic therapy (PDT) are dating back to the nineteenth century [176] and continue to play a prominent role in the field of molecular photomedicine [28], [34], [177]. Today, in medicine and life sciences light is also exploited as a valuable tool to precisely manipulate cells and tissues [178] or to release physiologically
Reaction cascades: Towards metabolic pathways
In living organisms, biocatalytic reaction networks are used to produce the vast variety of molecules found in nature. The combination of several enzymatic transformations in concurrent one-pot processes (multi-enzymatic cascade reactions) also plays an important role in biotechnology and modern synthetic chemistry [237], [238]. In this context, attempts are also made to establish simple model systems for mimicking metabolism-like substrate transformations using multiple enzymatic cascade
Outlook and conclusions
The unique concept of constructing photochemical enzyme models is continuously expanding. Many succesful applications in the fields of chemistry, biology and medicine have already been demonstrated, which otherwise could hardly have been achieved. Compared to non-photochemical approaches for the design of artificial enzymes, the strategy of employing catalytic reaction cycles driven by light offers several important advantages. In their inactive resting state such catalytic systems can be
Acknowledgements
Financial support by the Austrian Science Foundation (FWF projects P25038 “Functional Light-Responsive Metal Carbonyl Systems” and W1250 “NanoCell”), the Austrian Climate and Energy Funds (FFG project 841186 “Artificial Photosynthesis”), and the European Commission COST Action CM1202 “Supramolecular Photocatalytic Water Splitting” (PERSPECT-H2O) is gratefully acknowledged.
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