Recent publications by the Senge Group
Fundamentals of Porphyrin Chemistry: A 21st Century Approach Now Available
The new book: Fundamentals of Porphyrin Chemistry: A 21st Century Approach is Now Available
Written by Prof. Dr. Senge and colleagues, this book features discussion of the basics of porphyrin synthesis and structure, as well as that of related molecules, and the current and future roles that porphyrins play in chemical transformations, materials design and synthesis, energy capture and transduction, human health, and the environment.
Shaker, Y. M.; Omar, M. A.; Grover, N.; Senge, M. O. Facile synthesis of porphyrin-conjugates as amphiphilic modified photosensitizer structures of m-THPP bearing carbamate, carboxylate and sulfonate linkers. Journal of Porphyrins and Phthalocyanines, 2022, 26, 638—647.
5,10,15,20-Tetrakis(3-hydroxyphenyl)porphyrin (m-THPP) bearing various nitrogen and sulfur containing heterocycles, aromatic, aliphatic and alicyclic residues covalently linked to the oxygen atom of the meta-hydroxy group of the porphyrin unit were synthesized in good yields as potential photosensitizers for photodynamic therapy (PDT). These new amphiphilic conjugates were designed to use three different polar linkers (carboxylate, sulfonate, and carbamate linker units)via the reaction of m-THPP with nicotinoyl chloride hydrochloride (carboxylate linker), 5-bromothiophene-2-sulfonyl chloride (sulfonate linker), phenyl isocyanate, 3,5-bis(trifluoromethyl)phenyl isocyanate, hexyl isocyanate and cyclohexyl isocyanate (carbamate linker). The heterocycles employed are 5- and 6-membered rings with different solubility characteristics.
Kingsbury, C.J.; Kielmann, M.; Twamley, B.; Senge, M.O. Self-Organization of Porphyrin—POM Dyads: Nonplanar Diacids and Oxoanions in Low-Dimensional H-Bonding Networks. Molecules 2022, 27, 7060.
Coordinating the spatial arrangement of electroactive partners is crucial to designable molecular electronics and photonics. Porphyrins are ubiquitous reaction centers in nature; synthetic porphyrins, in the crystallographic solid state, are often coerced into monolithic stacks, inhibiting reactivity. Using the principles of self-organization, and by exploiting charge-balance principles, we can manipulate nonplanar porphyrins into one- and two-dimensional hydrogen-bonded polymers, with polyoxometalate (POM) and bifunctional counter-anions serving as linkers.
Teeuwen, P. C. P., Melissari, Z., Senge, M. O., Williams, R. M.. Metal Coordination Effects on the Photophysics of Dipyrrinato Photosensitizers. Molecules 2022, 27, 6967.
ithin this work, we review the metal coordination effect on the photophysics of metal dipyrrinato complexes. Dipyrrinato complexes are promising candidates in the search for alternative transition metal photosensitizers for application in photodynamic therapy (PDT). These complexes can be activated by irradiation with light of a specific wavelength, after which, cytotoxic reactive oxygen species (ROS) are generated. The metal coordination allows for the use of the heavy atom effect, which can enhance the triplet generation necessary for generation of ROS.
Khurana, B.; Ouk, T.-S.; Lucas, R.; Senge, M.O.; Sol, V. Photosensitizer-Hyaluronic Acid Complexes for Antimicrobial Photodynamic Therapy (APDT). J. Porphyrins Phthalocyanines 2022, A-I
The number of drug-resistant bacteria is increasing significantly. To combat such issues, antimicrobial PDT (aPDT) provides an efficient way to eliminate these species efficiently, cost-effectively, and more importantly, without the associated mechanism of resistance. The hemisynthesis and synthesis of photosensitizers such as polyaminated chlorin-p6 and 5-(4-aminophenyl)-10,15,20-tris(4-𝑁-methylpyridinium)porphyrin triiodide and their water stable and soluble formulation with hyaluronic acid bio-polymer (PS-HA) is reported.
Gierlich, P.; Rodrigues, L.; Schaberle, F.A.; Callaghan, S.; Gomes-da-Silva, L.C.; Senge, M.O. Trimethoxyphenyl-BODIPYs as Probes for Lysosome Staining. J. Porphyrins Phthalocyanines 2022, A-L
BODIPYs have been extensively used for biological imaging owing to their high fluorescent quantum yields of stability toward photobleaching. In this work, zwitterionic groups were introduced into trimethoxyphenyl-BODIPY derivatives to improve their water-solubility. The impact of the substitution pattern of the methoxy groups in the phenyl motif and of the alkyl groups at different positions of the BODIPY core was also investigated. Three novel water-soluble trimethoxyphenyl-BODIPYs, herein designated as BDP-12, BDP-13 and BDP-14, were then evaluated as potential markers for lysosome staining.
Donohoe, C.; Leroy-Lhez, S.; Senge, M.O.; Gomes-da-Silva, L.C. POLYTHEA — The Opportunities and Challenges of Doctoral Training Networks. J. Porphyrins Phthalocyanines 2022, A-F, doi:10.1142/S1088424622500250.
Photodynamic therapy (PDT) is a multi-component therapy which relies on the delivery of a photosensitizer drug and light in the presence of oxygen to mediate a therapeutic anti-cancer or anti-microbial effect. As a multi-component therapy, a multidisciplinary research approach is required to achieve success with the application of PDT. The POLYTHEA network, a project funded under the Marie Skołodowska-Curie Actions (MSCA) of Horizon 2020 (H2020) program, provided an opportunity to build a collaboration of laboratories across Europe with the necessary expertise required for the different facets of PDT.
Ishizuka, T.; Grover, N.; Kingsbury, C.J.; Kotani, H.; Senge, M.O.; Kojima, T. Nonplanar Porphyrins: Synthesis, Properties, and Unique Functionalities. Chem. Soc. Rev. 2022,Advance Article doi:10.1039/D2CS00391K.
Porphyrins are variously substituted tetrapyrrolic macrocycles, with wide-ranging biological and chemical applications derived from metal chelation in the core and the 18Π aromatic surface. Under suitable conditions, the porphyrin framework can deform significantly from regular planar shape, owing to steric overload on the porphyrin periphery or steric repulsion in the core, among other structure modulation strategies. Adopting this nonplanar porphyrin architecture allows guest molecules to interact directly with an exposed core, with guest-responsive and photoactive electronic states of the porphyrin allowing energy, information, atom and electron transfer within and between these species. This functionality can be incorporated and tuned by decoration of functional groups and electronic modifications, with individual deformation profiles adapted to specific key sensing and catalysis applications. Nonplanar porphyrins are assisting breakthroughs in molecular recognition, organo- and photoredox catalysis; simultaneously bio-inspired and distinctly synthetic, these molecules offer a new dimension in shape-responsive host—guest chemistry. In this review, we have summarized the synthetic methods and design aspects of nonplanar porphyrin formation, key properties, structure and functionality of the nonplanar aromatic framework, and the scope and utility of this emerging class towards outstanding scientific, industrial and environmental issues.
Donohoe, C.; Schaberle, F.A.; Rodrigues, F.M.S.; Gonçalves, N.P.F.; Kingsbury, C.J.; Pereira, M.M.; Senge, M.O.; Gomes-da-Silva, L.C.; Arnaut, L.G. Unraveling the Pivotal Role of Atropisomerism for Cellular Internalization. J. Am. Chem. Soc. 2022, Article ASAP
The intrinsic challenge of large molecules to cross the cell membrane and reach intracellular targets is a major obstacle for the development of new medicines. We report how rotation along a single C—C bond, between atropisomers of a drug in clinical trials, improves cell uptake and therapeutic efficacy. The atropisomers of redaporfin (a fluorinated sulfonamide bacteriochlorin photosensitizer of 1135 Da) are separable and display orders of magnitude differences in photodynamic efficacy that are directly related to their differential cellular uptake. We show that redaporfin atropisomer uptake is passive and only marginally affected by ATP depletion, plasma proteins, or formulation in micelles. The α4 atropisomer, where meso-phenyl sulfonamide substituents are on the same side of the tetrapyrrole macrocycle, exhibits the highest cellular uptake and phototoxicity.
Lewandowska-Andralojc, A.; Gacka, E.; Pedzinski, T.; Burdzinski, G.; Lindner, A.; O′Brien, J. M.; Senge, M. O.; Siklitskaya, A.; Kubas, A.; Marcinia, B.; Walkowiak-Kulikowska, J.. Understanding structure—properties relationships of porphyrin linked to graphene oxide through Π—Π-stacking or covalent amide bonds. Scientific Reports 2022, 12, 13420.
Two graphene oxide nanoassemblies using 5-(4-(aminophenyl)-10,15,20-triphenylporphyrin (TPPNH2) were fabricated by two synthetic methods: covalent (GO-CONHTPP) and noncovalent bonding. GO-CONHTPP was achieved through amide formation at the periphery of GO sheets and the hybrid material was fully characterized by FTIR, XPS, Raman spectroscopy, and SEM.
Senge, M.O., Meindl, A. Organic Synthesis and Reactivity of Porphyrins. In Fundamentals of Porphyrin Chemistry (eds P.J. Brothers and M.O. Senge). 2022
The synthesis and functionalization of porphyrins is a long-established but still burgeoning field. It has seen many advances, from studies on the fundamental natural heme and chlorophyll systems, to an ever-expanding array of complex tetrapyrroles that are used in a multitude of modern applications ranging from biochemistry to catalysis, medicine to materials science. This has been facilitated by significant progress in the preparation, modification, and transformation of the fundamental porphyrin macrocycle, bringing us to a point where, perhaps not all, but almost any desired porphyrin can be prepared in a rational manner. This is based on close to 10ߙ000 publications to date on the synthetic organic chemistry of porphyrins, and this chapter gives a general overview of the current state-of-the-art methodologies that illustrate the fundamental concepts in porphyrin chemistry and will highlight contemporary studies with illustrative examples.
Senge, M.O. It's All in the Name. In Fundamentals of Porphyrin Chemistry (eds P.J. Brothers and M.O. Senge). 2022
The chapter reviews past and current ways of naming and classifying synthetic and natural porphyrinoids and covers the older Fischer and modern IUPAC-IUB nomenclature. The latter provides a convenient system of naming standard porphyrin derivatives, but has not kept pace with the explosive development of new classes of porphyrins with altered macrocycle arrangements. Thus, informal, contemporary systems of nomenclature in use in the literature are covered as well.
Senge, M.O. An Introduction to Porphyrins for the Twenty-First Century. In Fundamentals of Porphyrin Chemistry (eds P.J. Brothers and M.O. Senge). 2022
Porphyrin is the ligand that encapsulates iron in heme, the active site of the red blood cell protein hemoglobin. In plants, porphyrins in the form of magnesium complexes are the key players in photosynthesis. Porphyrin colors are also encountered in daily life. Many colors around us are related to porphyrin biosynthesis and catabolism. The early development of the field of porphyrin chemistry and biochemistry, dating back to the mid-nineteenth century, was driven by the quest to understand the components and function of leaf pigments and of blood. In the later part of the twentieth century and into the twenty-first century, developments have built on increasing sophistication in synthetic chemistry. Porphyrins have found use as catalysis in industrial syntheses of drug molecules. Porphyrins are the fundament of many groundbreaking developments in modern science, and thus knowledge of their fundamentals is essential.
_
In Fundamentals of Porphyrin Chemistry: A 21st Century Approach, a team of distinguished researchers delivers a compact and accessible introduction to the broad field of porphyrin chemistry. It discusses the basics of porphyrin synthesis and structure, as well as that of related molecules, and the current and future roles that porphyrins play in chemical transformations, materials design and synthesis, energy capture and transduction, human health, and the environment.
Norvaiša, K., O'Brien, J. E., Osadchuk, I., Twamley, B., Borovkov, V., & Senge, M. O. Importance of Molecular Symmetry for Enantiomeric Excess Recognition by NMR., Chem. Commun., 2022,58, 5423-5426
Recently prochiral solvating agents (pro-CSA) became a spotlight for the detection of enantiopurity by NMR. Chemical shift non-equivalency in achiral hosts introduced by the presence of chiral guest yields observable resonance signal splitting correlating to the enantiomeric excess (e.e.). In this work, symmetry is our lens to explain porphyrin-based supramolecular receptors′ activity in a chiral environment. Based on extensive NMR analyses of the atropisomeric receptors, host symmetry is shown to be affected by porphyrin nonplanarity and further desymmetrized in the presence of a chiral guest. We have formulated a simple, symmetry-based protocol that can be used to identify pro-CSA candidates. As such, the exposed porphyrin inner core (N—H), with its strong hydrogen bond abilities, for the first time, has been exploited in enantiomeric composition analysis. Our approach in e.e. detection by N—H signals appearing in a previously underutilized region of the spectrum (below 0 ppm.), shows chemical shifts (the e.e. dependent splitting) three times more sensitive to enantiomeric compositions than previously reported systems. The findings are complemented by extensive 2D NMR studies, including the first reporting of e.e. dependent δΔ in non-hydrogen NMR, and supporting by density functional theory (DFT) calculations.
Gierlich, P.; Mucha, S.G.; Robbins, E.; Gomes-da-Silva, L.C.; Senge, M.O. One-Photon and Two-Photon Photophysical Properties of Tetrafunctionalized Temoporfin (m-THPC) Derivatives as Potential Agents for Two-Photon Induced Photodynamic Therapy. 11. doi.org/10.1002/cptc.202100249
Photodynamic therapy (PDT) is a cancer treatment, which exploits a photosensitizing drug and light to produce reactive oxygen species that can cause selective damage to the target tissue. The second-generation photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC) is a widely used, clinically tested, and commercially available drug with the market formulation known as Foscan. m-THPC was used as a starting point to obtain a library of compounds with improved optical properties. Substitution, esterification and Sonogashira coupling reactions were employed to modify the m-THPC skeleton. Aldehyde and carboxylic acid moieties provided the possibility to enhance the two-photon absorption (TPA) cross-section while being suitable synthetic handles in the design of drug delivery systems. Characterization of their linear photophysical properties (fluorescence quantum yield, fluorescence lifetime and singlet oxygen quantum yield) was followed by the evaluation of their potential use in a non-linear absorption regime. The calculated TPA cross-section values indicate even a 2.6-fold enhancement at the TPA maximum (69.3±10.0ߕGM), compared to m-THPC (26.7±4.0ߕGM), which proves that functionalization of the m-THPC core leads to the improvement of the non-linear optical properties. Thus, tetrafunctionalized m-THPC derivatives are promising candidates for application in two-photon induced PDT.
Büchner, R.; Vaz da Cruz, V.; Grover, N.; Charisiadis, A.; Fondell, M.; Haverkamp, R.; Senge, M.O.; Föhlisch, A. Fundamental Electronic Changes upon Intersystem Crossing in Large Aromatic Photosensitizers: Free Base 5,10,15,20-Tetrakis(4-Carboxylatophenyl)Porphyrin. Phys. Chem. Chem. Phys. 2022, 24, 7505—7511
Free base 5,10,15,20-tetrakis(4-carboxylatophenyl)porphyrin stands for the class of powerful porphyrin photosensitizers for singlet oxygen generation and light-harvesting. The atomic level selectivity of dynamic UV pump — N K-edge probe X-ray absorption spectroscopy in combination with time-dependent density functional theory (TD-DFT) gives direct access to the crucial excited molecular states within the unusual relaxation pathway. The efficient intersystem crossing, that is El-Sayed forbidden and not facilitated by a heavy atom is confirmed to be the result of the long singlet excited state lifetime (Qx 4.9 ns) and thermal effects. Overall, the interplay of stabilization by conservation of angular momenta and vibronic relaxation drive the de-excitation in these chromophores.
Andexer, J. N.; Beifuss, U.; Brasholz, M.; Breinbauer, R.; Breugst, M.; Dumele, O.; Ernst, M.; Ganardi, R.; Giese, M.; Gulder, T. A. M.; Hüttel, W.; Kath-Schorr, S.; Körber, K.; Kordes, M.; Lindel, T.; Mück-Lichtenfeld, C.; Niemeyer, J.; Pfau, R.; Pfrengle, F.; Pietruszka, J.; Röckl, J. L.; Schaschke, N.; Sebode, H.; Senge, M. O.; Straub, B. F.; Teichert, J.; Waldvogel, S. R.; Werner, T.; Winter, C. Trendbericht Organische Chemie, Nachrichten aus der Chemie 2022, 70, 42—69.
-
Norvaiša, K.; Maguire, S.; Donohoe, C.; O′Brien, J.E.; Twamley, B.; Gomes-da-Silva, L.C.; Senge, M.O. Steric Repulsion Induced Conformational Switch in Supramolecular Structures. Chem. Eur J. 2022, 28, doi:10.1002/chem.202103879.
Inspired by the rigidified architecture of ′picket-fence′ systems, we propose a strategy utilizing strain to impose intramolecular tension in already peripherally overcrowded structures leading to selective atropisomeric conversion. Employing this approach, tuneable shape-persistent porphyrin conformations were acquired exhibiting distinctive supramolecular nanostructures based on the orientation of the peripheral groups. The intrinsic assemblies driven by non-covalent bonding interactions form supramolecular polymers while encapsulating small molecules in parallel channels or solvent-accessible voids. The developed molecular strain engineering methodologies combined with synthetic approaches have allowed the introduction of the pivalate units creating a highly strained molecular skeleton. Changes in the absorption spectrum indicated the presence of severe steric repulsions between the peripheral groups which were confirmed by single crystal X-ray analysis. To release the steric strain introduced by the peripheral units, thermal equilibration strategies were used to selectively convert the most abundant atropisomer to the desirable minor one.
Cao, N.; Riss, A.; Corral-Rascon, E.; Meindl, A.; Auwärter, W.; Senge, M.O.; Ebrahimi, M.; Barth, J.V. Surface-Confined Formation of Conjugated Porphyrin-Based Nanostructures on Ag(111). Nanoscale 2021, 13, 19884—19889
Porphyrin-based oligomers were synthesized from the condensation of adsorbed 4-benzaldehyde-substituted porphyrins through the formation of CC linkages, following a McMurry-type coupling scheme. Scanning tunneling microscopy, non-contact atomic force microscopy, and X-ray photoelectron spectroscopy data evidence both the dissociation of aldehyde groups and the formation of CC linkages. Our approach provides a path for the on-surface synthesis of porphyrin-based oligomers coupled by CC bridges — as a means to create functional conjugated nanostructures.
Bettini, S.; Grover, N.; Ottolini, M.; Mattern, C.; Valli, L.; Senge, M.O.; Giancane, G. Enantioselective Discrimination of Histidine by Means of an Achiral Cubane-Bridged Bis-Porphyrin. Langmuir 2021, 37, 13882—13889, doi:10.1021/acs.langmuir.1c02377.
A Langmuir film of cubane-bridged bisporphyrin (H 2 por-cubane-H2 por) at the air/water interface was developed and characterized. The floating film was successfully employed for the chiral discrimination between L - and D -histidine. The enantioselective behavior persisted after the deposition of the film on a solid support using the Langmuir—Schaefer method. Distinct absorption and reflection spectra were observed in the presence of L- or D-histidine, revealing that conformational switching was governed by the interaction between H2 por-cubane-H2 por and the histidine enantiomer. The mechanism of chiral selection was investigated using an ad hoc modified nulling ellipsometer, indicating the anti-conformation was dominant in the presence of L -histidine, whereas the presence of D -histidine promoted the formation of tweezer conformation.
