My research interests are centered on the theoretical investigation of a wide variety of chemical processes that include organic and biological systems, catalytic and electrochemical phenomena as well as experimental studies using fluorescence spectroscopy.  An integral part of my research involves the development of methods and techniques that facilitate these theoretical studies.  To exemplify my research interests, I am presenting below brief descriptions of several research projects, finalized and published, unpublished or currently ongoing.  Both undergraduate and graduate students have been involved in these projects. 

A.  Chemical reaction dynamics in gas phase and in solutions

One main project currently ongoing in my lab focuses on studying the chemical dynamics of hydrogen abstraction from hydrofluorocarbons by hydroxyl and other radicals.  These processes are important atmospheric and environmental reactions.  The chemical dynamics of some of these hydrogen abstraction reactions have been successfully investigated using variational transition state theory (VTST) with multidimensional tunneling contributions.  The main advantage of the VTST is that it allows calculations of the dynamical quantities based on the local information on the potential energy surface (PES).  The accuracy of the dynamics results is however limited by the level of electronic structure theory underlying the dynamics so part of this study involves generating accurate PES using hybrid density functional theory (HDFT) with specific reaction parameters (SRP).  The use of HDFT methods is preferred because they are easily parameterized and affordable electronic structure methods.  HDFT-SPR studies have been completed for the HO + CH3F [A1, A2], HO + CH2F2 [A3], and HO + CHF3 [A4] reactions.  Unpublished studies focus on hydrogen abstraction from hydrofluoroethanes and hydrofluoropropanes by hydroxyl radical or other radicals [A5-A10].

Another important ongoing project is dealing with the mechanism and the electronic effects that govern the oxidation of amines by quinones.  Quinones act as cofactor in amine oxidases, and free quinones (not covalently bound to the enzyme) have also been identified in the cell.  The role of these free quinones is not completely understood, however it is believed that some of them oxidize primary amines to aldehydes.  An ongoing investigation looks into the reactions of benzoquinones and naphthoquinones with a number of amines, with special focus on the reactivity of the quinone toward amine oxidation, the position of amine attack and its dependence of amine reactivity, the structures of the intermediates and of the final products [A11-A14].

Another research interest concerns the chemical transformations of carbenes, and two such studies focusing on the rearrangements involving both hydrogen and carbon migrations are already published [A15, A16], one of them in prestigious Science magazine.  This particular study, dealing with rearrangements in methylcyclobutylhalocarbenes, present an extraordinary example of a reaction involving exclusively through tunneling involving large carbon motions.  Additional unpublished work looked at the temperature dependence of the rate constants and of the activation energies, the determination of 13C kinetic isotope effect, and the relative distribution of the product for the isotopic rearrangements in methylcyclobutylhalocarbenes.  Another unpublished project was looking at the unimolecular rearrangement of fluorophenoxycarbene.

[A1] Mikel, S. E.; Albu, T. V. “Hybrid Density Functional Theory Investigation of the Hydrogen Abstraction Reaction of Fluoromethane by the Hydroxyl Radical,” J. Undergrad. Chem. Res. 2006, 5, 75-81.

[A2] Albu, T. V.; Swaminathan, S. “Hybrid Density Functional Theory with Specific Reaction Parameter: Hydrogen Abstraction Reaction of Fluoromethane by the Hydroxyl Radical,” J. Phys. Chem. A. 2006, 110, 7663-7671.

[A3] Albu, T. V.; Swaminathan, S. “Hybrid Density Functional Theory with a Specific Reaction Parameter: Hydrogen Abstraction Reaction of Difluoromethane by the Hydroxyl Radical,” J. Molec. Model. 2007, 13, 1109-1121.

[A4] Albu, T. V.; Swaminathan, S. “Hybrid Density Functional Theory with a Specific Reaction Parameter: Hydrogen Abstraction Reaction of Trifluoromethane by the Hydroxyl Radical,” Theor. Chem. Acc. 2007, 117, 383-395.

[A5] De Silva, N. W. S. V. N. Tennessee Technological University, M.S. thesis, 2007.

[A6] Senevirathna, W. Tennessee Technological University, M.S. thesis, 2009.

[A7] Bryant, D. University of Tennessee at Chattanooga, Final Report, 2015.

[A8] Albu, T. V.; Dray, T.; De Silva, N. W. S. V. N. “Hybrid Density Functional Theory with Specific Reaction Parameter: Hydrogen Abstraction from Fluoroethanes,” in preparation.

[A9] Albu, T. V.; Bryant, D.; De Silva, N. W. S. V. N. “Hydrogen Abstraction from Fluoropropanes. I. Abstraction by 3O radical,” in preparation.

[A10] Albu, T. V.; De Silva, N. W. S. V. N.; Senevirathna, W. “Hydrogen Abstraction from Fluoropropanes. II. Abstraction by Hydroxyl Radical,” in preparation.

[A11] Fernando, J. A. C. Tennessee Technological University, M.S. thesis, 2009.

[A12] Rathnayake, L. Tennessee Technological University, M.S. thesis, 2013.

[A13] Lee, K. University of Tennessee at Chattanooga, Honors thesis, 2019.

[A14] Kim, J.; Kang, M. J.; Albu, T.V.; Fernando, J. A. C.; Rathnayake, L. “Reactivity Study on Substituted Benzoquinones with Lysine,” in preparation.

[A15] Albu, T. V.; Lynch, B. J.; Truhlar, D. G.; Goren, A.; Hrovat, D. A.; Borden, W. T.; Moss, R. A. “Dynamics of 1,2-Hydrogen Migration in Carbenes and Ring Expansion in Cyclopropylcarbenes” J. Phys. Chem. A. 2002, 106, 5323-5338.

[A16] Zuev, P. S.; Sheridan, R. S.; Albu, T. V.; Truhlar, D. G.; Hrovat, D. A.; Borden, W. T. “Carbon Tunneling from a Single Quantum State,” Science 2003, 299, 867-870. 

B.  Algorithms for efficient chemical dynamics calculations

This research focuses on the development and the application of methodologies to create semiglobal and global PES to be used in dynamics calculations in conjunction with VTST calculations.  The technique developed, called multi-configuration molecular mechanics (MCMM) algorithm, has been used to create semiglobal PES for reactive systems [B1].  MCMM combines electronic structure theory information (energy, gradient, Hessian) at a small number of points on the surface with molecular mechanics potential functions in a form of a nonadiabatic Hamiltonian matrix.  Advancements of the method involve the use of only few Hessian elements calculated using electronic structure theory while the other elements are calculated using molecular mechanics [B2].  Future developments could involve establishing a similar methodology where the molecular mechanics potentials will be replaced by electronic structure theory potentials describing different electronic states.  One application of this new method is on creating reactive PES for electron transfer processes, particularly electrochemical processes.

[B1] Albu, T. V.; Corchado, J. C.; Truhlar, D. G. “Molecular Mechanics for Chemical Reactions: A Standard Strategy for Using Multiconfiguration Molecular Mechanics for Variational Transition State Theory with Optimized Multidimensional Tunneling,” J. Phys. Chem. A. 2001, 105, 8465-8487.

[B2] Lin, H.; Pu, J.; Albu, T. V.; Truhlar, D. G. “Efficient Molecular Mechanics for Chemical Reactions:  Multiconfiguration Molecular Mechanics using Partial Electronic Structure Hessians,” J. Phys. Chem. A. 2004, 108, 4112-4124. 

C.  Computational investigation of electrocatalytic and surface processes

Fuel cell development has generated special interest in the past decade.  The biggest problem in the fuel cell industry is the cathodic process of oxygen reduction.  The best electrocatalysts for the oxygen reduction reaction (ORR) are platinum and its alloys.  The limited number of theoretical studies on ORR is due to their enhanced difficulty considering that the methodology should include the electrode and its electrochemical potential, the reaction center, and the solvent.  The original studies of uncatalyzed and Pt-catalyzed ORR date back to my graduate work [C1-C3].  A more recent project in our lab was focused on the performance of HDFT methods for ORR [C4].  It was found that HDFT methods with half Hartree-Fock exchange contribution give more accurate results that the generic HDFT methods and should be more appropriate for applications to bigger reaction systems.  Other unpublished work focuses on the dependence of the electrode model (for which we use clusters containing 4, 6, 7, or 10 platinum atoms) on the adsorption energies of intermediate species, especially hydroperoxyl radical.

[C1] Anderson, A. B.; Albu, T. V. “Ab initio Determination of Reversible Potentials and Activation Energies for Outer-Sphere Oxygen Reduction to Water and the Reverse Oxidation Reaction,” J. Am. Chem. Soc. 1999, 121, 11855-11863.

[C2] Anderson, A. B.; Albu, T. V. “Catalytic Effect of Platinum on Oxygen Reduction: An Ab Initio Model Including Dependence on the Electrode Potential,” J. Electrochem. Soc. 2000, 147, 4229-4238.

[C3] Albu, T. V.; Anderson, A. B. “Improvements to an Ab initio Model for Electrochemical Processes: Application to the Outer-Sphere Oxygen Reduction,” Electrochim. Acta 2001, 46, 3001-3013.

[C4] Albu, T. V., Mikel, S. E. “Performance of Hybrid Density Functional Theory Methods toward Oxygen Electroreduction over Platinum,” Electrochim. Acta 2007, 52, 3149-3159. 

D.  Modeling properties of molecules, ions and materials

Electron ionization mass spectrometry is used in structural investigation of organic compounds but the method has some limitations due to its lack of discrimination between stereoisomers.  We carried out a computational study [D1] to explain the observed differences in the abundances of fragment ions obtained in mass spectrometry of the cis,cis and trans,trans diastereoisomers of four 2(r)-R-2,4(R),6(S)-trimethyl-1,3-dioxane derivatives.  We found that there are more than one stable ion conformations for each of the investigated ions, but due to relatively small rotation barrier height, the different conformers are unlikely to be involved in distinct fragmentation pathways.  Energy profiles along the torsional coordinates and factors influencing the relative stability of ion conformations were presented and discussed.  

The synthesis and the NMR characterization of a series of eight alloxan-based thiosemicarbazones and semicarbazones were reported, and these compounds were found to exhibit a strongly hydrogen-bonded hydrazinic proton that is part of a characteristic six-membered ring.  This proton is highly deshielded and resonates far downfield in the proton NMR spectra.  Electronic structure theory calculations have been used to investigate the structure and other molecular properties of these eight compounds [D2].  The relationship between the 1H and 13C NMR chemical shifts and various geometric parameters was investigated, and linear relationships for proton peaks that are involved in hydrogen-bond interactions were found.  A study on the isomerism and NMR properties of thiosemicarbazones has also been published [D3] while another study on molecular properties of acetylpyrazine and quinolinecarboxaldehyde thiosemicarbazones [D4] has not been published yet.

Another finalized and published project dealt with investigating the association patterns of hydrogen fluoride and water [D5].  The focus was on determining the average strength of hydrogen bond interactions between various types of hydrogen/protons and oxygen or fluorine, and their dependence with respect to the size of the model (i.e., the number of H2O and HF molecules).  Preferred association patterns were also investigated.  The results should be useful for statistical modeling of water-hydrogen fluoride mixtures. 

Synthetic diamond obtained by chemical vapor deposition has been shown great potential for use in a number of areas.  Pure diamond is an isolator but doped diamond can act as either p-type or n-type semiconductor.  The nature and the properties of the dopants is, in some cases, not completely understood.  In an initial investigation carried out during my graduate studies, using cluster models and HDFT methods, a large number of dopants were explored to determine the method limitations and to search among various potential n-type dopants [D6].  A more recent study focuses on possible interpretations for the n-type conductivity observed for boron-doped diamond with hydrogen and sulfur co-doping [D7].  A possible explanation for the n-type behavior, created by co-doping diamond films with boron and sulfur, is given in terms of thermally activated electron donation from an SVS (V is vacancy) donor to a BB acceptor band considering that both lie deep in the band gap.

Another finalized project in my lab focuses on modeling Ru complexes with fluorine-containing phosphines or phosphites as ligands [D8].  HOMO-LUMO gaps have been calculated using ab initio methods and were found to correlate well with UV-Vis experimental results.  A linear behavior was also found between the HOMO-LUMO gap and the number of fluorine atoms in the ligand. A series of 3 metal complexes containing crown thioether ligands were also investigated theoretically to determine their optimized geometries and HOMO-LUMO gaps and to correlate these properties with complexes reactivity toward DNA [D9].

[D1] Albu, T. V. “Hybrid Density Functional Theory Study of Fragment Ions Generated during Mass Spectrometry of 1,3-Dioxane Derivatives,” Rapid Commun. Mass Spectrom. 2006, 20, 1871-1876.

[D2] De Silva, N. W. S. V. N.; Lisic, E. C.; Albu, T. V. “Hybrid Density Functional Theory Investigation of a Series of Alloxan-Based Thiosemicarbazones and Semicarbazones,” Central Eur. J. Chem. 2006, 4, 646-665.

[D3] De Silva, N. W. S. V. N.; Albu, T. V. “A Theoretical Investigation on the Isomerism and the NMR Properties of Thiosemicarbazones,” Central Eur. J. Chem. 2007, 5, 396-419.

[D4] Rathnayake, L. Tennessee Technological University, M.S. thesis, 2013.

[D5] Baburao, B.; Visco, D. P. Jr.; Albu, T. V. “Association Patterns in (HF)m(H2O)n (m + n = 2-8) Clusters,” J. Phys. Chem. A. 2007, 111, 7940-7956.

[D6] Albu, T. V.; Anderson, A. B.; Angus, J. C. “Dopants in Diamond Nanoparticles and Bulk. Density Functional Study of Substitutional B, N, P, SB, S, PN, O, NN, and Interstitial H,” J. Electrochem. Soc. 2002, 149, E143-E147.

[D7] Cai, Y.; Zhang, T.; Anderson, A. B.; Angus, J. C.; Kostadinov, L. N.; Albu, T. V. “The Origin of Shallow n-type Conductivity in Boron-Doped Diamond with H or S Co-Doping: Density Functional Theory Study,” Diam. Relat. Mater. 2006, 15, 1868-1877.

[D8] Lee, J. P.; Hankins , M. J.; Riner, A. D.; Albu, T. V. "Synthetic, Structural and Spectroscopic Studies of Mixed Sandwich Ru(II) Complexes Involving h6-p-Cymene with Monodentate Fluorine-Containing Phosphines or Phosphites," J. Coord. Chem. 2016, 69, 20-38.

[D9] Kim, J.; Cardenal, A. D.; Greve, H. J.; Chen, W.; Vashi, H.; Grant, G.; Albu, T. V. " Interaction with Calf-Thymus DNA and Photoinduced Cleavage of pBR322 by Rhodium(III) and Iridium(III) Complexes Containing Crown Thioether Ligands," Inorg. Chim. Acta 2018, 469, 484-494. 

E.  Fluorescence Studies of Protein Modifications Induced by Quinones and on DNA Interactions with Metal Complexes

Quinones are commonly found in the nature and the general environment and exhibit interesting biological activities and cytotoxicity.  In an initial study [E1], we showed that p-benzoquinone was able to modify a model protein, ribonuclease A (RNase), in a complex manner including adduct formation and protein aggregation.  Among other experimental observations, it was found that the modified RNase exhibited less intense fluorescence and slightly higher anisotropy than the unmodified RNase.  A degree of protein modification was defined based on the fluorescence intensity, and it was found to correlate well with the concentration of p-benzoquinone.  The study was extended to include substituted quinones [E2], and it was found the chlorobenzoquinone is more potent in modifying RNase than p-benzoquinone and both are more potent than methylbenzoquinone. The modification of RNase was found to be enhanced by the presence of very low concentrations of Cu2+ ions but not by other metal ions [E3].  The modification induced by benzoquinones [E4] and naphthoquinones [E5] on lysozyme, an amyloidal protein, were also studied and it was found that the modifications are more significant than in the case of RNase. Also, investigating lysozyme modifications by p-benzoquinone at different conditions shows that more significant modifications occur at higher pH conditions and higher temperatures [E4].

Fluorescence spectroscopy was also used to investigate the binding interactions between three rhodium(III) and iridium(III) crown thioether complexes and calf-thymus DNA [E6].  It was found that rhodium complexes are effective binders while the iridium complex is not.

[E1] Kim, J.; Vaughn, A. R.; Cho, C.; Albu, T.V.; Carver, E. A. “Modifications of Ribonuclease A Induced by p-Benzoquinone,” Bioorg. Chem. 2012, 40, 92-98.

[E2] Kim, J.; Albu, T. V.; Vaughn, A. R.; Kang, S. M.; Carver, E. A.; Stickle, D. M. “Comparison Study on Ribonuclease A Modifications Induced by Substituted p-Benzoquinones,” Bioorg. Chem. 2015, 59, 106-116.

[E3] Kim, J.; Ewald, J. M.; Albu, T. V. “Effects of Metal Ions of Protein Modifications Induced by p-Benzoquinone,” in preparation.

[E4] Kim, J.; Thomas, C. A.; Ewald, J. M.; Kurien, N. M.; Booker, M. E.; Greve, H. J.; Albu, T. V. “Studies on Lysozyme Modifications Induced by Substituted p-Benzoquinones,” Bioorg. Chem2019, 85, 386-398.

[E5] Kim, J.; Thomas, C. A.; Kurien, N. M.; Ewald, J. M.; Booker, M. E.; Greve, H. J.; Albu, T. V. “Studies on Protein Modifications Induced by Naphthoquinones,” in preparation.

[E6] Kim, J.; Cardenal, A. D.; Greve, H. J.; Chen, W.; Vashi, H.; Grant, G.; Albu, T. V. " Interaction with Calf-Thymus DNA and Photoinduced Cleavage of pBR322 by Rhodium(III) and Iridium(III) Complexes Containing Crown Thioether Ligands," Inorg. Chim. Acta 2018, 469, 484-494. 

Summary and concluding remarks

As presented above, my research interests focus on modeling, using modern theoretical methods, a wide range of chemical processes including gas-phase reactions relevant to atmospheric chemistry and combustion, organic and biological chemistry in solution, catalysis and electrocatalysis.  An additional area of research focuses on investigating experimentally protein modifications using fluorescence spectroscopy.  Most projects are suitable for undergraduate students.  The presented research projects span over many fields of chemistry and provide opportunities for multiple and productive collaborations.