About

Thomas Lectka is the Jean and Norman Scowe Professor in the Department of Chemistry at Johns Hopkins University. He graduated from Oberlin College with highest honors in Chemistry in 1985 and received his Ph.D. from Cornell University in 1990, studying with Professor John McMurry. His postdoctoral studies included work as an Alexander von Humboldt Fellow at Heidelberg with Rolf Gleiter and as an NIH Fellow at Harvard University with Professor David Evans. He joined the Johns Hopkins faculty in 1994 and was promoted to his current professorship in 2012. His research employs the tools of organic, fluorine, and inorganic chemistry to develop new reactions of academic and pharmaceutical interest, with a focus on metal catalysis and photochemistry. Key research goals include aliphatic fluorination and selective bond activation. His group studies reaction mechanisms through various techniques such as kinetics, EPR, NMR, voltammetry, crystallography, and advanced computations like DFT and MP2. Notable contributions include the synthesis of the first fluoronium ion in solution, as predicted by DFT theory, and the development of fundamentally new reactions and species with unusual properties. Professor Lectka has received numerous awards, including an NIH First Award, NSF Career Award, Eli Lilly Grantee Award, Sloan Fellowship, Dreyfus-Teacher-Scholar Award, a John Simon Guggenheim Memorial Fellowship, and the ACS Arthur C. Cope Scholar Award in 2024. He has also been recognized as the ACS Maryland Chemist of the Year in 2017. His work is characterized by a focus on reaction development, mechanistic studies, and the creation of novel chemical species.

Research topics

• Chemistry
• Organic chemistry
• Computational chemistry
• Photochemistry
• Stereochemistry
• Combinatorial chemistry
• Medicinal chemistry

Selected publications

• Introduction: Fluorine-Specific Interactions

  Chemical Reviews · 2025-11-26 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• A highly selective C–H bond fluorination unlocks conformational reporting in a complex natural product derivative

  Chemical Science · 2025-01-01 · 6 citations

  articleOpen accessSenior authorCorresponding

  In our fluorination of the antibiotic salinomycin and its simple derivatives, a chain of discoveries provided us a unique path to a selective result, unlocking low-noise conformational reporting by 19 F NMR in a widely studied medicinal scaffold.

  PublisherOA PDFDOI

• A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins

  eLife · 2025-06-05

  preprintOpen access

  Abstract Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an in vivo chemiluminescent reporter of ApoB (LipoGlo) that does not disrupt ApoB function. Thus, the LipoGlo model is an ideal system for identifying novel mechanisms of ApoB modulation and, due to the ability of zebrafish to generate many progeny, is particularly amenable to large-scale phenotypic drug screening. Here, we report a screen of roughly 3000 compounds that identified 49 unique ApoB-lowering hits. Nineteen hits passed orthogonal screening criteria. A licorice root component, enoxolone, significantly lowered B-lps only in animals that express a functional allele of the nuclear hormone receptor Hepatocyte Nuclear Factor 4⍺ (HNF4⍺). Consistent with this result, inhibitors of HNF4⍺ also reduce B-lp levels. These data demonstrate that mechanism(s) of action can be rapidly determined from a whole animal zebrafish phenotypic screen. Given the well documented role of HNF4⍺ in human B-lp biology, these data validate the LipoGlo screening platform for identifying small molecule modulators of B-lps that play a critical role in a leading cause of worldwide mortality.

  PublisherDOI

• The Fluorinative Skeletal Rearrangement of Lumisantonin: An Unanticipated Dual Role of Selectfluor

  The Journal of Organic Chemistry · 2025-06-19 · 5 citations

  articleSenior authorCorresponding

  Synthetic chemists have been intrigued by the rearrangement reactions of α-santonin and santonin-derived natural products for over 150 years. Herein, we report an unprecedented fluorinative skeletal rearrangement of lumisantonin in the presence of Selectfluor. To our surprise, mechanistic studies suggest that the rearrangement proceeds through a thermal two-electron process, rather than a photochemical radical fluorination mechanism as initially conceived. A series of synthetic experiments and transition state studies reveal that the reaction is governed by an unusual, concerted strain-release electrophilic fluorination, followed by rearrangement of the carbon skeleton to generate a key tertiary carbocation intermediate. This intermediate is then readily trapped by either the tetrafluoroborate counteranion (Balz-Schiemann-type fluorination) or acetonitrile (Ritter-type amination), affording novel fluorinated derivatives of isophotosantonic lactone, as confirmed by single crystal X-ray crystallography.

  PublisherDOI

• Lewis Acid‐Initiated Cleavage of a Large Ionophore: Molecular Deactivation by Potassium Ion Binding

  ChemMedChem · 2025-10-28

  articleSenior authorCorresponding

  to a large ionophoric natural product effects a fast cleavage of the molecule into two distinct fragments. The exploration of the mechanism implicates acidification of the carboxylic acid through metal coordination, and protonation of unbound molecules in a catalyzed cleavage; merck molecular force field (MMFF) conformational searches and density functional theory (DFT) calculations support these hypotheses. When a competing, more tightly binding metal such as K + is introduced, Zn(II) binding is precluded, and the rate of cleavage drops drastically. It is believed that these results may be helpful in understanding the role that metal ions play in drug degradation as well as illuminating their general role in altering the reactivity of ionophores.

  PublisherDOI

• 2.6 Direct Fluorination of C(sp3)—H Bonds

  2025-12-03

  book-chapterSenior author

  Abstract Ever since the legendary era of Henri Moissan and his isolation of fluorine gas, chemists have sought to harness new reagent technology for achieving fluorination at C—H positions. The development of new reagents, from H-fluorobenzenesulfonimide (NFSI) to Selectfluor, has aided in the quest. In this review, we explore methods for the fluorination of otherwise unactivated C—H bonds, with a particular focus on aliphatic substrates through predominately radical-based approaches.

  PublisherDOI

• Catalysis of Free C–C Bond Rotation: C–F---H–X H-Bonds Find a Catalytic Role

  Journal of the American Chemical Society · 2025-02-10

  articleSenior authorCorresponding

  There are few dynamic processes in organic chemistry that are more central to the molecular structure than C-C bond rotation. It is notable, however, that there exist few (if any) cases in which its hindered variants can actually be catalyzed. In this communication, we report a unique model system for the clear documentation of the catalysis of 360° C-C bond rotation that employs a transient but key N-H---F-C hydrogen bond as a linchpin and secondary "dual" charge-induced n → π* interactions and ion pairing effects that bolster catalysis.

  PublisherDOI

• A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins

  eLife · 2025-06-05

  preprintOpen access

  Abstract Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an in vivo chemiluminescent reporter of ApoB (LipoGlo) that does not disrupt ApoB function. Thus, the LipoGlo model is an ideal system for identifying novel mechanisms of ApoB modulation and, due to the ability of zebrafish to generate many progeny, is particularly amenable to large-scale phenotypic drug screening. Here, we report a screen of roughly 3000 compounds that identified 49 unique ApoB-lowering hits. Nineteen hits passed orthogonal screening criteria. A licorice root component, enoxolone, significantly lowered B-lps only in animals that express a functional allele of the nuclear hormone receptor Hepatocyte Nuclear Factor 4⍺ (HNF4⍺). Consistent with this result, inhibitors of HNF4⍺ also reduce B-lp levels. These data demonstrate that mechanism(s) of action can be rapidly determined from a whole animal zebrafish phenotypic screen. Given the well documented role of HNF4⍺ in human B-lp biology, these data validate the LipoGlo screening platform for identifying small molecule modulators of B-lps that play a critical role in a leading cause of worldwide mortality.

  PublisherDOI

• Author response: A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins

  2025-06-05

  peer-reviewOpen access

  Lipoproteins are essential for lipid transport in all bilaterians. A single Apolipoprotein B (ApoB) molecule is the inseparable structural scaffold of each ApoB-containing lipoprotein (B-lps), which are responsible for transporting lipids to peripheral tissues. The cellular mechanisms that regulate ApoB and B-lp production, secretion, transport, and degradation remain to be fully defined. In humans, elevated levels of vascular B-lps play a causative role in cardiovascular disease. Previously, we have detailed that human B-lp biology is remarkably conserved in the zebrafish using an in vivo chemiluminescent reporter of ApoB (LipoGlo) that does not disrupt ApoB function. Thus, the LipoGlo model is an ideal system for identifying novel mechanisms of ApoB modulation and, due to the ability of zebrafish to generate many progeny, is particularly amenable to large-scale phenotypic drug screening. Here, we report a screen of roughly 3000 compounds that identified 49 unique ApoB-lowering hits. Nineteen hits passed orthogonal screening criteria. A licorice root component, enoxolone, significantly lowered B-lps only in animals that express a functional allele of the nuclear hormone receptor Hepatocyte Nuclear Factor 4⍺ (HNF4⍺). Consistent with this result, inhibitors of HNF4⍺ also reduce B-lp levels. These data demonstrate that mechanism(s) of action can be rapidly determined from a whole animal zebrafish phenotypic screen. Given the well documented role of HNF4⍺ in human B-lp biology, these data validate the LipoGlo screening platform for identifying small molecule modulators of B-lps that play a critical role in a leading cause of worldwide mortality.

  PublisherDOI

• Selective Fluorination of Complex Molecules: Late-Stage Functionalization

  Chemical Reviews · 2025-07-21 · 21 citations

  reviewSenior authorCorresponding

  It has been more than 160 years since chemists first performed fluorination reactions on organic molecules. Scores of fluorination reagents and hundreds of worthwhile methods have been developed over the intervening years. Meanwhile, workers in the field are increasingly aware of the benefits of incorporating fluorine atoms into bioactive molecules. Therefore, the emergence of “late-stage fluorination” in the first decade of the 21st century is both natural and well-justified─an extant compound, off the shelf, can be converted more efficiently to a fluorinated product than through a de novo approach. It is worth noting that chemists’ attempts to fluorinate complex molecules began sporadically decades ago before the concept of “late-stage” was first proposed. In this Perspective, we aim to present a comprehensive series of late-stage fluorination strategies, with the spotlight primarily focused on single-atom modifications of complex molecules (although incidental examples of polyfluorination are addressed), including natural products, analogues, and pharmaceuticals. Both the nucleophilic and electrophilic sources of fluorine are examined.

  PublisherDOI

Recent grants

• Lewis Base Directed Intermolecular Hydrogen Atom Transfer

  NSF · $500k · 2021–2025

• NIH Grant R01GM064559

  NIH · $2.0M · 2010

• Polycomponent Catalysis in Organic Synthesis

  NSF · $405k · 2012–2015

• NIH Grant R29GM054348

  NIH · $524k · 2002

• New Approaches to Site-Selective Fluorination

  NSF · $420k · 2015–2018

Frequent coauthors

• Maxime A. Siegler

  95 shared

• Travis Dudding

  Brock University

  65 shared

• Cody Ross Pitts

  64 shared

• Maxwell Gargiulo Holl

  45 shared

• Muhammad Kazim

  37 shared

• Andrew E. Taggi

  FMC (United States)

  35 shared

• Stefan Andrew Harry

  Center for Cancer Research

  32 shared

• Michael T. Scerba

  National Institutes of Health

  31 shared

Labs

• The Lectka GroupPI

Awards & honors

• NIH First Award
• NSF Career Award
• Eli Lilly Grantee Award
• Sloan Fellowship
• Dreyfus-Teacher-Scholar Award