Lindsey Lab research

Our research focuses on the chemistry underlying photosynthesis, and makes use of synthetic chemistry, mechanistic chemistry, and diverse analytical methods. Of particular interest are artificial photosynthesis and the possible prebiotic origin of photosynthesis.

Artificial photosynthesis

Artificial photosynthesis embodies the longstanding challenge to create photosynthetic-like processes in purely chemical constructs. Our work in this area has focused on (1) the development of powerful new de novo routes for the synthesis of tetrapyrrole pigments, including porphyrins, chlorins, and bacteriochlorins, and (2) exploiting access to novel tetrapyrrole building blocks to prepare and investigate elaborate molecular architectures for efficient light-harvesting. The synthetic routes to chlorins and bacteriochlorins incorporate stabilizing structural motifs for these otherwise sensitive hydroporphyrins. We now have the ability to prepare almost “naked” analogues of chlorophyll as well as highly functionalized analogues, which together enable questions to be addressed about the role of substituents at the perimeter of the macrocycle in tuning the spectral, photochemical, and self-assembly processes of chlorophyll molecules. We are in the midst of developing analogous methodology for bacteriochlorins. The vast amount of prior work in artificial photosynthesis has used porphyrins as surrogates for (bacterio)chlorins, which lack the all-important red or near-infrared spectral features of the latter molecules. Thus, access to novel synthetic (bacterio)chlorins presents a whole suite of unprecedented research opportunities. In this regard, we are investigating a variety of ways to create organized assemblies of (bacterio)chlorins that function as efficient light-harvesting systems. We also continue to develop databases for incorporation into PhotochemCAD. The spectroscopic studies of the artificial photosynthetic constructs, including elaborate multipigment architectures prepared by covalent or self-assembly approaches, are carried out by our longtime collaborators David F. Bocian and Dewey Holten. Other collaborators in our artificial photosynthesis research are David Tiede and Lin X. Chen.

Biomedical

The development of versatile synthetic methods for creating hydroporphyrins (chlorins and bacteriochlorins) has opened a number of biomedical research opportunities. The strong absorption of these pigments in the red or near-infrared region is ideally suited for photomedicine where deep tissue penetration of light is required. We are working to make water-soluble, bioconjugatable chlorins and bacteriochlorins for use in photodynamic therapy (PDT) in treatment of a wide variety of medical indications ranging from wound infections to cancerous tumors. The biomedical work is done in collaboration with Michael Hamblin and coworkers at the Wellman Center for Photomedicine at Harvard Medical School.

Origin of life

The question of the origin of life remains one of the great unsolved problems of modern science. A source of energy is essential to drive prebiotic metabolism and self-replicating systems. In this regard, we are investigating photochemical processes of relevance to the creation of prebiotic molecules and as an energy source to drive prebiotic molecular evolution. A key aspect of our work is to understand routes for the origin of the essential pigments (e.g., tetrapyrrole macrocycles) that underlie extant photosynthesis, and may be of relevance for the emergence of an early, Hadean- or Archaean-era proto-photosynthesis.