title: Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid.
abstract: The results of infrared spectroscopic investigations into the band assignments, vibrational relaxation, and solvation dynamics of the common anti-tuberculosis treatment Isoniazid (INH) are reported. INH is known to inhibit InhA, a 2-trans-enoyl-acyl carrier protein reductase enzyme responsible for the maintenance of cell walls in Mycobacterium tuberculosis but as new drug-resistant strains of the bacterium appear, next-generation therapeutics will be essential to combat the rise of the disease. Small molecules such as INH offer the potential for use as a biomolecular marker through which ultrafast multidimensional spectroscopies can probe drug binding and so inform design strategies but a complete characterization of the spectroscopy and dynamics of INH in solution is required to inform such activity. Infrared absorption spectroscopy, in combination with density functional theory calculations, is used to assign the vibrational modes of INH in the 1400-1700 cm(-1) region of the infrared spectrum while ultrafast multidimensional spectroscopy measurements determine the vibrational relaxation dynamics and the effects of solvation via spectral diffusion of the carbonyl stretching vibrational mode. These results are discussed in the context of previous linear spectroscopy studies on solid-phase INH and its usefulness as a biomolecular probe.
authors.affiliation: Department of Physics, University of Strathclyde, SUPA, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Shaw
authors.affiliation: Department of Physics, University of Strathclyde, SUPA, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom.
authors.forename: Katrin
authors.initials: K
authors.lastname: Adamczyk
authors.affiliation: Department of Physics, University of Strathclyde, SUPA, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom.
authors.forename: Pim W J M
authors.initials: PW
authors.lastname: Frederix
authors.affiliation: Department of Physics, University of Strathclyde, SUPA, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom.
authors.forename: Niall
authors.initials: N
authors.lastname: Simpson
authors.affiliation: Strathclyde Institute for Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Robb
authors.affiliation: STFC Rutherford Appleton Laboratory, Central Laser Facility, Research Complex at Harwell, Didcot OX11 0QX, United Kingdom.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Greetham
authors.affiliation: STFC Rutherford Appleton Laboratory, Central Laser Facility, Research Complex at Harwell, Didcot OX11 0QX, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Towrie
authors.affiliation: STFC Rutherford Appleton Laboratory, Central Laser Facility, Research Complex at Harwell, Didcot OX11 0QX, United Kingdom.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Parker
authors.affiliation: Strathclyde Institute for Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Hoskisson
authors.affiliation: Department of Physics, University of Strathclyde, SUPA, 107 Rottenrow East, Glasgow G4 0NG, United Kingdom.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hunt
mesh_terms: D007538:Isoniazid / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D012995:Solubility; D013055:Spectrophotometry, Infrared; D014732:Vibration
chemical_list: D007538:Isoniazid