Richard Manderville

Prof Manderville
Email: 
rmanderv@uoguelph.ca
Phone number: 
519-824-4120 ext. 53963/52252
Office: 
SSC 3243
Lab: 
SSC 3241
Website links: 
Google Scholar Profile

Education and Employment

B.Sc. Honours., 1986, Queen's University, Kingston, Canada
Ph.D., 1992, Physical Organic Chemistry, Queen's University (Erwin Buncel)
Postdoctoral Research Associate 1992-1995, BioOrganic Chemistry, University of Virginia (Sidney. M. Hecht)
Assistant Professor of Chemistry, 1995-2001, Wake Forest University, Winston-Salem, North Carolina, U.S.A.
Associate Professor of Chemistry, 2001-2004, Wake Forest University, Winston-Salem, North Carolina, U.S.A.
Associate Professor of Chemistry, 2004-2009, University of Guelph, Guelph, ON, Canada
Professor of Chemistry & Toxicology, 2009-Present, University of Guelph, Guelph, ON, Canada
Director of Toxicology Program, 2010-Present, University of Guelph, ON, Canada

Highlights

  • NSERC Discovery Grant Evaluation Group member for Chemistry (1504), 2021
  • Member of the Editorial Advisory Board for Toxicology Research, 2020-present
  • NSERC RTI Grant Evaluation Group Member for Chemistry (1504), 2015-2016
  • Editorial Board Member for Toxins, 2011-present

Research

Biochemical Toxicology

Our research in the area of biochemical toxicology focuses on the structural and biological impact of C8-aryl-2′-deoxyguanosine (C8-aryl-dG) adducts (addition products) that are a common lesion type and may contain N-, O- or C-aryl linkages (denoted N-, O- and C-linked adducts). For N-linked adducts, three common structural motifs in duplex DNA (i.e., the major-groove B-type, the intercalated base-displaced stacked S-type, or the minor-groove wedge W-type) have been characterized. In general, N-linked C8-aryl-dG adducts that exhibit potent mutagenicity have planar polycyclic structures and favor the S-type or W-type duplexes with the bulky lesion in the syn-conformation. N-linked C8-aryl-dG lesions also have the propensity to cause two-base deletions within XCG (X = adduct) sequences. The long-term goal of this project is to advance our fundamental understanding of how bulky C8-aryl-dG adducts containing various linkage types are processed in cells. To achieve this goal, synthetic organic chemistry is utilized to convert dG into various C8-aryl-dG adducts. The modified nucleoside is converted into a phosphoramidite and incorporated into oligonucleotide substrates using solid-phase DNA synthesis to afford adducted DNAs containing a single C8-aryl-dG adduct. Optical spectroscopies (UV-vis, fluorescence and circular dichroism) are then used to determine the impact of the lesion on duplex DNA. The adducted DNAs are also used as substrates in primer-extension assays with various DNA polymerase enzymes to determine the biological impact of the modified base. Students interested in molecular toxicology, organic and biochemistry, are encouraged to read some of our recent publications and inquire about possible projects in this area of biochemical toxicology.

For N-linked adducts, three common structural motifs in duplex DNA (i.e., the major-groove B-type, the intercalated base-displaced stacked S-type, or the minor-groove wedge W-type) have been characterized.

Biosensing Applications

Fluorescence is one of the most powerful bioanalytical methods and fluorescent biosensors are designed to change their fluorescent intensities or wavelengths in response to physiological changes including pH, solvent polarity, viscosity, redox reactions, metal ions and apoptosis. This aspect of our research focuses on the utility of internal fluorescent DNA bases to report molecular target binding by DNA aptamers. DNA aptamers are selected in vitro from random libraries for their ability to bind molecular targets with high affinity and specificity. Modification of DNA aptamers with internal fluorescent replacements can be used for diagnostics. The challenge is to select a fluorescent dye with sufficient brightness, chemical and photochemical stability, and emission sensitivity to target binding without perturbing aptamer affinity for the target. Our published research in this area has focused on defining the fluorescent sensing properties of aryl-modified nucleobases within DNA aptamers. While these bases undergo excitation in the UV (320-350 nm) and lack sufficient brightness for real-life applications, we demonstrated their utility for monitoring aptamer-target binding through a change in DNA topology (duplex→G-quadruplex (GQ) exchange) and through direct interaction of the modified nucleobase with the target. We are now in the process of synthesizing and testing visibly emissive dyes that undergo changes in excitation wavelength and emission intensity upon aptamer binding to protein targets. Students interested in organic chemistry and biochemistry are encouraged to read some of our recent publications and inquire about possible projects in this area of research.

Instrumentation

Optical spectroscopy (UV-vis, Fluorescence), DNA Synthesis to prepare chemically modified oligonucleotides with high-performance liquid chromatography (HPLC) for oligonucleotide purification

Current Members

Darian Blanchard MSc student
Thomas Cservenyi MSc student
Ms. Florence Berger Visiting MSc student, ETH Zurich
Ms. Anne Verwey MSc
Mike Sproviero, PhD
Aaron Witham, PhD
Kaila Fadock, MSc

Past Members

Alireza Omumi, PhD
Chris McLaughlin, MSc
Mark Sun, MSc
Jamie La, MSc
Christine Frenette, MSc
Jen Weishar, MSc
Robert Paugh, MSc
Katie Rankin (née Schlit), PhD
Michael Kuska, MSc
Prof. Mei Li Visiting Scholar from School of the Environment, Nanjing University, Nanjing, China

Publications

109. Van Riesen, A.J.; Fadock, K.L.; Deore, P.S.; Desoky, A.; Manderville, R.A.; Sowlati-Hashjin, S.; Wetmore, S.D. Manipulation of a DNA Aptamer-Protein Binding Site through Arylation of a Distal Guanine Residue. Org. Biol. Chem. 2017, Themed issue on Nucleic Acid Modifications, Manuscript ID: OB-ART-08-2017-001986, Revision requested.

108. Fadock, K.L.; Manderville, R.A. DNA Aptamer-Target Binding Motif Revealed Using a Fluorescent Guanine Probe: Implications for Food Toxin Detection. ACS Omega 2017, 2, 4955-4963.

107. Kathuria, P.; Sharma, P.; Manderville, R.A.; Wetmore, S.D. Molecular Modeling of the Major DNA Adduct Formed from Food Mutagen Ochratoxin A in NarI Two-Base Deletion Duplexes: Impact of Sequence Context and Adduct Ionization on Conformational Preference and Mutagenicity. Chem. Res. Toxicol. 2017, 30, 1582-1591.

106. McLellan, N.L.; Manderville, R.A. Toxic mechanisms of microcystins in mammals. Toxicol. Res. 2017, 6, 391-405.

105. Manderville, R.A.; Wetmore, S.D. Mutagenicity of Ochratoxin A: Role for a Carbon-Linked C8-Deoxyganosine Adduct? J. Agric. Food Chem. 2017, 65, 7097-7105.

104. Olaoye, O.O.; Manderville, R.A. Aptamer Utility in Sensor Platforms for the Detection of Toxins and Heavy Metals. J. Toxins 2017, 4, 12.

103. Manderville, R.A.; Wetmore, S.D. Understanding the Mutagenicity of O-Linked and C-Linked Guanine DNA Adducts: A Combined Experimental and Computational Approach. Chem. Res. Toxicol. 2017, 30, 177-188.

102. Cservenyi, T.Z.; Van Riesen, A.J.; Berger, F.D.; Desoky, A.; Manderville, R.A. A Simple Molecular Rotor for Defining Nucleoside Environment within a DNA Aptamer-Protein Complex. ACS Chem. Biol. 2016, 11, 2576-2582.

101. Blanchard, J. M., Manderville, R. A. An internal charge transfer-DNA platform for fluorescence sensing of divalent metal ions. Chem. Commun. 2016, 52, 9586-9588.

100. Fadock, K. L., Manderville, R. A., Sharma, P., and Wetmore, S. D. Optimization of fluorescent 8-heteroaryl-guanine probes for monitoring protein-mediated duplex?G-quadruplex exchange. Org. Biomol. Chem. 2016, 14, 4409-4419.

99. Manderville, R.A.; Wetmore, S.D. C-Linked 8-Aryl Guanine Nucleobase Adducts: Biological Outcomes and Utility as Fluorescent Probes. Chem. Sci. 2016, 7, 3482-3493.

98. Blanchard, D.J.M.; Fadock, K.L.; Sproviero, M.; Deore, P.S.; Cservenyi, T.Z.; Manderville, R.A.; Sharma, P.; Wetmore, S.D. Photophysical properties of push–pull 8-aryldeoxyguanosine probes within duplex and G-quadruplex structures. J. Mater. Chem. C 2016, 4, 2915-2924.

97. Blanchard, D.J.M.; Cservenyi, T.Z.; Manderville, R.A. Dual fluorescent deoxyguanosine mimics for FRET detection of G-quadruplex folding. Chem. Commun. 2015, 51, 16829-16831.

96. Sproviero, M.; Verwey, A.M.R.; Witham, A.A.; Manderville, R.A.; Sharma, P.; Wetmore, S.D. Enhancing Bulge Stabilization through Linear Extension of C8-Aryl- Guanine Adducts to Promote Polymerase Blockage or Strand Realignment to Produce a C:C Mismatch. Chem. Res. Toxicol. 2015, 28, 1647-1658.

95. Witham, A.A.; Verwey, A.M.R.; Sproviero, M.; Manderville, R.A.; Sharma, P.; Wetmore, S.D. Chlorine functionalization of a model phenolic C8-guanine adduct increases conformational rigidity and blocks extension by a Y-family DNA polymerase. Chem. Res. Toxicol. 2015, 28, 1346-1356.

94. Sproviero, M.; Fadock, K.L.; Witham, A.A.; Manderville, R.A. Positional impact of fluorescently modified G-tetrads within polymorphic human telomeric G-quadruplex structures. ACS Chem. Biol. 2015, 10, 1311-1318.

93. Sharma, P.; Majdi Yazdi, M.; Merriman, A.; Manderville, R.A.; Wetmore, S.D. Influence of the linkage type and functional groups in the carcinogenic moiety on the conformational preferences of damaged DNA: Structural and energetic characterization of carbon and oxygen-linked C8-phenolic-guanine adducts. Chem. Res. Toxicol. 2015, 28, 782-796.

92. Witham, A.A.; Sharma, P.; Wetmore, S.D.; Gabryelski, W.; Manderville, R.A. Chlorine substitution promotes phenyl radical loss from C8-phenoxy-2'-deoxy-guanosine adducts: implications for biomarker identification from chlorophenol exposure. J. Mass Spectrom. 2015, 50, 81-87.

91. Sproviero, M.; Verwey, A.M.R.; Rankin, K.M.; Witham, A.A.; Soldatov, D.V.; Manderville, R.A.; Fekry, M.I.; Sturla, S.J.; Sharma, P.; Wetmore, S.D. Structural and biochemical impact of C8-aryl-guanine adducts within the NarI recognition DNA sequence: influence of aryl ring size on targeted and semi-targeted mutagenicity. Nucleic Acids Res. 2014, 42, 13405-13421.

90. Sharma, P.; Manderville, R.A.; Wetmore, S.D. Structural and energetic characterization of the major DNA adduct formed from the food mutagen ochratoxin A in the NarI hotspot sequence: influence of adduct ionization on the conformational preferences and implications for the NER propensity. Nucleic Acids Res. 2014, 42, 11831-11845.

89. Verwey, A.M.R.; Witham, A.A.; Li, M.; Manderville, R.A. Mutagenicity Analysis of C8-Phenoxy-Guanine in the NarI Recognition DNA Sequence. J. Toxins 2014, 1, 6.

88. Sproviero, M.; Manderville, R.A. Harnessing the G-Tetrad Scaffold for Fluorescent Detection Strategies Within G-Quadruplex Forming Aptamers. Chem. Comm. 2014, 50, 3097-3099.

87. Sproviero, M.; Rankin, K. M.; Witham, A. A.; Manderville, R. A., Utility of 5'-O-2,7-Dimethylpixyl for Solid-Phase Synthesis of Oligonucleotides Containing Acid-Sensitive 8-Aryl-Guanine Adducts. J. Org. Chem. 2014, 79 (2), 692-699.

86. Sproviero, M.; Manderville, R. A., Harnessing G-tetrad scaffolds within G-quadruplex forming aptamers for fluorescence detection strategies. Chem. Commun., 2014, 50, 3097-3099.

85. Sproviero, M.; Fadock, K. L.; Witham, A. A.; Manderville, R. A.; Sharma, P.; Wetmore, S. D., Electronic tuning of fluorescent 8-aryl-guanine probes for monitoring DNA duplex-quadruplex exchange. Chem. Sci. 2014, 5 (2), 788-796.

84. Kuska, M. S.; Witham, A. A.; Sproviero, M.; Manderville, R. A.; Majdi Yazdi, M.; Sharma, P.; Wetmore, S. D., Structural Influence of C8-Phenoxy-Guanine in the NarI Recognition DNA Sequence. Chem. Res. Toxicol. 2013, 26 (9), 1397-1408.

83. Kuska, M.S.; Majdi Yazdi, M.; Witham, A.A.; Dahlmann, H.A.; Sturla, S.J.; Wetmore, S.D.; Manderville, R.A. Influence of Chlorine Substitution on the Hydrolytic Stability of Biaryl Ether Nucleoside Adducts Produced by Phenolic Toxins. J. Org. Chem. 2013, 78, 7176-7185.

82. Sharma, P.; Manderville, R. A.; Wetmore, S. D. Modeling the Conformational Preference of the Carbon-Bonded Covalent Adduct Formed upon Exposure of 2′-Deoxyguanosine to Ochratoxin A. Chem. Res. Toxicol. 2013, 26, 803-816.

81. Rankin, K.M.; Sproviero, M.; Rankin, K.; Sharma, P.; Wetmore, S.D.; Manderville, R.A. C8-Heteroaryl-2′-deoxyguanosine Adducts as Conformational Fluorescent Probes in the NarI Recognition Sequence. J. Org. Chem. Featured Article 2012, 77, 10498-10508.

80. Manderville, R.A.; Omumi, A.; Rankin (née Schlitt), K.M.; Wilson, K.; Millen, A.L.; Wetmore, S.D. A Fluorescent C-Linked C8-Aryl-Guanine Probe for Distinguishing syn from anti Structures in Duplex DNA. Chem. Res. Toxicol. 2012, 25, 1271−1282.

79. Omumi, A.; McLaughlin, C.K.; Ben-Israel, D.; Manderville, R.A. Application of a Fluorescent C-Linked Phenolic Purine Adduct for Selective N7-Metalation of DNA. J. Phys. Chem. B, 2012, 116, 6158-6165.

78. Tozlovanu, M.; Canadas, D.; Pfohl-Leszkowicz, A.; Frenette, C.; Paugh, R. J.; Manderville, R.A. Glutathione Conjugates of Ochratoxin A as Biomarkers of Exposure. Arh. Hig. Rada Toksikol. (Archives of Industrial Hygiene and Toxicology) 2012, 63, 417-427. Special Issue, Articles presented at the Symposium “Power of Fungi and Mycotoxins in Health and Disease” Primošten, Croatia, October 19-22, 2011.

77. Akman, S.A.; Adams, M.; Case, D.; Park, G.; Manderville, R.A. Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the supF Gene of the Mutation Reporter Plasmid pS189. Toxins 2012, 4, 267-280. Special Issue “Ochratoxins 2012”.

76. Witham. A.A.; Beach, D.G.; Gabryelski, W.; Manderville, R.A. Hydroxyl Radical-Induced Oxidation of a Phenolic C-Linked-2′-Deoxyguanosine Adduct Yields a Reactive Catechol. Chem. Res. Toxicol. 2012, 25, 315-325.

75. Pfohl-Leszkowicz, A.; Manderville, R.A. An Update on Direct Genotoxicity as a Molecular Mechanism of Ochratoxin A Carcinogenicity. Chem. Res. Toxicol. 2012, 25, 252-262.

74. Hadjeba-Medjdoub, K.; Tozlovanu, M.; Pfohl-Leszkowicz, A.; Frenette, C.; Paugh, R.J.; Manderville, R.A. Structure-Activity Relationships Imply Different Mechanisms of Action for Ochratoxin A-Mediated Cytotoxicity and Genotoxicity. Chem. Res. Toxicol. 2012, 25, 181-190.

73. Millen, A.L.; Kamenz, B.L.; Leavens, F.M.V.; Manderville, R.A.; Wetmore, S.D. Conformational Flexibility of C8-Phenoxyl-guanine Adducts in Deoxydinucleoside Monophosphates. J. Phys. Chem. B 2011, 115, 12993-13002.

72. Omumi, A.; Millen, A.L.; Wetmore, S.D.; Manderville, R.A. Fluorescent Properties and Conformational Preferences of C-Linked Phenolic-DNA Adducts. Chem. Res. Toxicol. 2011, 24, 1694-1709.

71. Schlitt, K.M.; Millen, A.L.; Wetmore, S.D.; Manderville, R.A. “An Indole-linked C8-Deoxyguanosine Nucleoside acts as a Fluorescent Reporter of Watson-Crick Versus Hoogsteen Base Pairing” Org. Biomol. Chem. 2011, 9, 1565-1571.

70. Omumi, A.; Beach, D.G.; Baker, M.; Gabryelski, W.; Manderville, R.A. “Post-Synthetic Guanine Arylation of DNA by Suzuki-Miyaura Cross-Coupling” J. Am. Chem. Soc. 2011, 133, 42-50.

69. Sagoo, S.; Beach, D.G.; Manderville, R.A.; Gabryelski, W. “Tautomerization in Gas-Phase Ion Chemistry of Isomeric C-8 Deoxyguanosine Adducts from Phenol-Induced DNA Damage” J. Mass. Spectrom. 2011, 46, 41-49.

68. Millen, A.L.; Churchill, C.D.M.; Manderville, R.A.; Wetmore, S.D. “Effect of Watson-Crick and Hoogsteen Base Pairing on the Conformational Stability of C8-Phenoxyl-2′-deoxyguanosine Adducts” J. Phys. Chem. B 2010, 114, 12995-13004.

67. Jennings-Gee, J.E.; Tozlovanu, M.; Manderville, R.A.; Miller, M.S.; Pfohl-Leszkowicz, A.; Schwartz, G.G. "Ochratoxin A: In Utero Exposure in Mice Induces Adducts in Testicular DNA" Toxins 2010, 2, 1428-1444.

66. Millen, A.L.; Manderville, R.A.; Wetmore, S.D. “Conformational Flexibility of C8-Phenoxyl-2′-deoxyguanosine Nucleotide Adducts” J. Phys. Chem. B 2010, 114, 4373-4382.

65. Mantle, P.G.; Faucet-Marquis, V.; Manderville, R.A.; Squillaci, B.; Pfohl-Leszkowicz, A. “Structures of Covalents Adducts Between DNA and Ochratoxin A: A New Factor in Debate About Genotoxicity and Human Risk Assessment” Chem. Res. Toxicol. 2010, 23, 89-98.

64. Manderville, R.A. “DNA Damage by Phenoxyl Radicals” In: Marc Greenberg, editor, Radical and Radical Ion Reactivity in Nucleic Acid Chemistry, John Wiley & Sons, 2009, Chapter 14, pp. 421-443.

63. Schlitt, M.K.; Sun, K.M.; Paugh, R.J.; Millen, A.L.; Navarro-Whyte, L.; Wetmore, S.D.; Manderville, R.A.“Concerning the Hydrolytic Stability of 8-Aryl-2'-deoxyguanosine Nucleoside Adducts: Implications for Abasic Site Formation at Physiological pH” J. Org. Chem. Featured Article 2009, 74, 5793-5802.

62. Manderville, R.A. “Structural and biological impact of radical addition reactions with DNA nucleobases” In: J. P. Richard, editor, Advances in Physical Organic Chemistry, Academic Press, 2009, Chapter 5, pp. 177-218.

61. Manderville, R.A.; Kropinski, A.M. “Approaches to the Compositional Analysis of DNA” Bacteriophages Methods and Protocols, Vol. 2: Molecular and Applied Aspects, Clokie, M.R.J; Kropinski, A.M. eds, Humana Press, 2009, Chapter 2, 11-17.

60. Pfohl-Leszkowicz, A.; Gabryelski, W.; Manderville, R.A. “Formation of 2′-Deoxyguanosine-Carbon 8-Bound Ochratoxin A Adduct in Rat Kidney DNA” Mol. Nutr. Food Res. 2009, 53, 154-155.

59. Pfohl-Leszkowicz, A.; Molinié, A.; Tozlovanu, M.; Manderville, R.A. “Combined Toxic Effects of Ochratoxin A and Citrinin, In Vivo and In Vitro” Food Contaminants Mycotoxins and Food Allergens, Siantar, D.P.; Trucksess, M.W.; Scott, P.M.; Herman, E.M. eds., American Chemical Society Symposium Series 1001, 2008, Chapter 3, pp. 56-79.

58. Manderville, R.A.; Pfohl-Leszkowicz, A. “Bioactivation and DNA Adduction as a Rationale for Ochratoxin A Carcinogenesis” World Mycotoxin Journal. 2008, 1, 357-367.

57. Weishar, J.L.; McLaughlin, C.K.; Baker, M.; Gabryelski, W.; Manderville, R.A. “Oxidation of a Biomarker for Phenol Carcinogen Exposure: Expanding the Redox Chemistry of 2′-Deoxyguanosine” Org. Lett. 2008, 10, 1839-1842.

56. Millen, A.L.; McLaughlin, C.K.; Sun, K.M.; Manderville, R.A.; Wetmore, S.D. “Computational and Experimental Evidence for the Structural Preference of Phenolic C-8 Purine Adducts. J. Phys. Chem. A 2008, 112, 3742-3753.

55. Frenette, C.; Paugh, R.J.; Tozlovanu, M.; Juzio, M.; Pfohl-Leszkowicz, A.; Manderville, R.A. “Structure-Activity Relationships for the Fluorescence of Ochratoxin A: Insight for Detection of Ochratoxin A Metabolites” Anal. Chim. Acta 2008, 617, 153-161. Special Issue, Articles presented at the 3rd International Symposium on Recent Advances in Food Analysis, Prague, Czech Republic, November 7-9, 2007.

54. Tomlinson, J.T.; Manderville, R.A. “Metal Coordination, Cytotoxicity, and DNA Interactions of the Prodigiosin Natural Products” Synthetic and Biophysical Studies of DNA Binding Compounds, Lee, M. and Strekowski, L. eds. 2007, pp. 197-237.

53. La, J.Q.-H.; Michaelides, A.A; Manderville, R.A. “Tautomeric Equilibria in Phenolic A-Ring Derivatives of Prodigiosin Natural Products” J. Phys. Chem. B 2007, 111, 11803-11811.

52. Pfohl-Leszkowicz, A.; Tozlovanu, M.; Manderville, R. A.; Peraica, M; Castegnaro, M.; Stefanovic, V. “New Molecular and Field Evidences for the Implication of Mycotoxins but not Aristolochic Acid in Human Nephropathy and Urinary Tract Tumor” Mol. Nutr. Food Res. 2007, 51, 1131-1146.

51. Sun, K. M.; McLaughlin, C. K.; Lantero, D. R.; Manderville, R. A. “Biomarkers for Phenol Carcinogen Exposure Act as pH-Sensing Fluorescent Probes” J. Am. Chem. Soc. 2007, 129, 1894-1895.

50. Park, G.; Tomlinson, J. T.; Misenheimer, J. A.; Kucera, G. L.; Manderville, R. A. “Photo-Induced Cytotoxicity of Prodigiosin Analogues” Bull. Korean Chem. Soc. 2007, 28, 49-52.

49. Pfohl-Leszkowicz, A.; Manderville, R. A. “Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans” Mol. Nutr. Food Res. 2007, 51, 61-99.

48.Tomlinson, J. T.; Park, G.; Misenheimer, J. A.; Kucera, G. L.; Hesp, K.; Manderville, R. A “Photoinduced Cytotoxicity and Thioadduct Formation by a Prodigiosin Analogue”Org. Lett. 2006, 8, 4951-4954.

47. Manderville, R. A.; Pfohl-Leszkowicz, A. “Genotoxicity of Chlorophenols and Ochratoxin A” Advances in Molecular Toxicology, Fishbein, J. C. ed., 2006, 1, pp. 73-118.

46. Tozlovanu, M.; Faucet-Marquis, V.; Pfohl-Leszkowicz, A.; Manderville, R. A. “Genotoxicity of the Hydroquinone Metabolite of Ochratoxin A: Structure-Activity Relationships for Covalent DNA Adduction” Chem. Res. Toxicol. 2006, 19, 1241-1247.

45. McLaughlin, C. K.; Lantero, D. R.; Manderville, R. A. “Conformational Properties of a Phototautomerizable Nucleoside Biomarker for Phenolic Carcinogen Exposure” J. Phys. Chem. A 2006, 110, 6224-6230.

44. Manderville, R. A. “Ambident Reactivity of Phenoxyl Radicals in DNA Adduction” Can. J. Chem. 2005, 83, 1261-1267.

43. Manderville, R. A. “A Case for the Genotoxicity of Ochratoxin A by Bioactivation and Covalent DNA Adduction” Chem. Res. Toxicol. 2005, 18, 1091-1097.

42. Dai, J.; Sloat, A. L.; Wright, M. W.; Manderville, R. A. “Role of Phenoxyl Radicals in DNA Adduction by Chlorophenol Xenobiotics Following Peroxidase Activation” Chem. Res. Toxicol. 2005, 18, 771-779.

41. Xu, M.; Nelson, G. B.; Moore, J. E.; McCoy, T. P.; Dai, J.; Manderville, R. A.; Ross, J. A.; Miller, M. S. “Induction of Cyp1a1 and Cyp1b1 and Formation of DNA Adducts in C57BL/6, Ba1b/c, and F1 Mice Following In Utero Exposure to 3-Methylcholanthrene” Toxicol. & Appl. Pharmacol. 2005, 209, 28-38.

40. Dai, J.; Park, G.; Perry, J.L., Il’ichev, Y.V.; Bow, D.A.J.; Pritchard, J.B.; Faucet, V.; Pfohl-Leszkowicz, A.; Manderville, R.A.; Simon, J.D. “Molecular Aspects of the Transport and Toxicity of Ochratoxin A” Acc. Chem. Res. 2004, 37, 874-881.

39. Faucet, V.; Pfohl-Leszkowicz, A., Dai, J.; Castegnaro, M.; Manderville, R.A. “Evidence for Covalent DNA Adduction by Ochratoxin A following Chronic Exposure to Rat and Subacute Exposure to Pig” Chem. Res. Toxicol. 2004, 17, 1289-1296.

38. Dai, J.; Wright, M. W.; Manderville, R.A. “An Oxygen-Bonded C8-Deoxyguanosine Nucleoside Adduct of Pentachlorophenol by Peroxidase Activation: Evidence for Ambident C8 Reactivity by Phenoxyl Radicals” Chem. Res. Toxicol. 2003, 16, 817-821.

37. Dai, J.; Wright, M. W.; Manderville, R. A. “Ochratoxin A Forms a Carbon-Bonded C8-Deoxyguanosine Nucleoside Adduct: Implications for C8 Reactivity by a Phenolic Radical” J. Am. Chem. Soc. 2003, 125, 3716-3717.

36. Manderville, R.A., Calcutt, M.W., Dai, J., Park, G., Gillman, I.G., Noftle, R.E., Mohammed, A.K., Dizdaroglu, M., Rodriguez, H., Akman, S.A. “Stoichiometric Preference in Copper-Promoted Oxidative DNA Damage by Ochratoxin A” J. Inorg. Biochem. 2003, 95, 87-96.

35. Buncel, E., Park, K. T., Dust, J. Manderville, R. A. “Concerning the Denticity of Dimsyl Anion in Meisenheimer Complexation” J. Am. Chem. Soc. 2003, 125, 5388-5392.

34. Perry, J. L.; Il’ichev, Y. V.; Kempf, V. R.; McClendon, J.; Park, G.; Manderville, R. A.; Rüker, F.; Dockal, M.; Simon, J. D. “Binding of Ochratoxin A Derivatives to Human Serum Albumin” J. Phys. Chem. B. 2003, 107, 6644-6647.

33. Buncel, E., Dust, J. M., Manderville, R. A., Tarkka, R.M. “Regioselectivity of Meisenheimer Complexation in Reaction of Oxygen-Centered Nucleophiles with Picryl Aryl Ethers. Polar Versus SET Mechanisms” Can. J. Chem, 2003, 81, 443-456.

32. Park, G.; Tomlinson, J.T.; Melvin, M.S.; Day, C.S.; Wright, M.W.; Manderville, R.A. “Zinc and Copper Complexes of Prodigiosin: Implications for Copper-Mediated Double-Strand DNA Cleavage” Org. Lett.. 2003, 5, 113-116.

31. Dai, J.; Park, G.; Wright, M.W.; Adams, M.; Akman, S.A.; Manderville, R.A. “Detection and Characterization of a Glutathione Conjugate of Ochratoxin A” Chem. Res. Toxicol., 2002, 15, 1581-1588.

30. Brow, M.E.; Dai, J.; Park, G.; Wright, M.W.; Gillman, I.G.; Manderville, R.A. “Photochemically Catalyzed Reaction of Ochratoxin A with D- and L-Cysteine” Photochem. & Photobiol., 2002, 76, 112-119.

29. Melvin, M.S.; Tomlinson, J.T.; Park, G.; Day, C.S.; Saluta, G.R.; Kucera, G.L.; Manderville, R.A. “Influence of the A-Ring on the Proton Affinity and Cytotoxicity of the Prodigiosins” Chem. Res. Toxicol., 2002, 15, 734-741.

28. Melvin, M.S.; Calcutt, M.W.; Noftle, R.E.; Manderville, R.A. “Influence of the A-ring on the Redox and Nuclease Properties of the Prodigiosins: Importance of the Bipyrrole Moiety in Oxidative DNA Cleavage” Chem. Res. Toxicol., 2002, 15, 742-748.

27. Melvin, M.S.; Wooton, K.E.; Rich, C.C.; Saluta, G.R.; Kucera, G.L.; Lindquist, N.; Manderville, R.A. “Copper-Nuclease Efficiency Correlates with Cytotoxicity for the 4-Methoxypyrrolic Natural Products” J. Inorg. Biochem., 2001, 87, 129-135.

26. Il’ichev, Y.V.; Perry, J.L.; Manderville, R.A.; Chignell, C.F.; Simon, J.D. “The pH-Dependent Primary Photoreactions of Ochratoxin A” J. Phys. Chem. B, 2001, 105, 11369-11376.

25. Calcutt, M.W.; Gillman, I.G.; Noftle, R.E.; Manderville, R.A. “Electrochemical Oxidation of Ochratoxin A: Correlation with 4-Chlorophenol” Chem. Res. Toxicol., 2001, 14, 1266-1272.

24. Keck, M.V.; Manderville, R.A.; Hecht, S.M. “Chemical and Structural Characterization of the Interaction of Bleomycin A2 with d(CGCGAATTCGCG)2. Efficient, Double-Strand DNA Cleavage Accessible without Structural Reorganization” J. Am. Chem. Soc., 2001, 123, 8690-8700.

23. Manderville, R. A. “Synthesis, Proton-Affinity and Anti-Cancer Properties of the Prodigiosin-Group Natural Products” Curr. Med. Chem.-Anti-Cancer Agents, 2001, 1, 195-218.

22. Melvin, M. S.; Tomlinson, J. T.; Saluta, G. R.; Kucera, G. L.; Lindquist, N.; Manderville, R. A. “Double-Strand DNA Cleavage by Copper·Prodigiosin” J. Am. Chem. Soc. 2000, 122, 6333-6334.

21. Gillman, I. G.; Clark, T. N.; Manderville, R. A. “Oxidation of Ochratoxin A by an Fe-Porphyrin System: Model for Enzymatic Activation and DNA Cleavage. Chem. Res. Toxicol. 1999, 12, 1066-1076.

20. Melvin, M. S.; Ferguson, D. C.; Lindquist, N.; Manderville, R. A. “DNA Binding by 4-Methoxypyrrolic Natural Products. Preference for Intercalation at AT Sites by Tambjamine E and Prodigiosin” J. Org. Chem., 1999, 64, 6861-6869.

19. Gillman, I.G.; Day, C.S.; Manderville, R.A. “Stepwise Formation of a Nonsymmetric Dinuclear Copper Complex of Ochratoxin A,” Inorg. Chem., 1998, 37, 6385-6388.

18. Borah,S.; Melvin, M.S.; Lindquist, N.; Manderville, R.A. “Copper-Mediated Nuclease Activity of a Tambjamine Alkaloid,” J. Am. Chem. Soc., 1998, 120, 4557-4562.

17. Ardus, J.A.; Gillman, I.G.; Manderville, R.A. “On the Role of Iron and Copper in DNA Cleavage by Ochratoxin A. Structure-Activity Relationships in Metal Binding and Copper-Mediated DNA Cleavage,” Can. J. Chem., 1998, 76, 907-918. Dedicatory issue for Erwin Buncel.

16. Gillman, I.G.; Yezek, J.M.; Manderville, R.A. “Ochratoxin A acts as a photoactivatable DNA cleaving agent,” Chem. Commun., 1998, 647-648.

15. Dust, J.M.; Manderville, R.A. “Carbon versus oxygen nucleophilic selectivity in the reaction of the aryloxide ions, 2,6- and 3,5-di-tert-butylphenoxide, with the 2-[(nitro)xaryl]-4,6-dinitro-benzotriazole 1-oxide series of super-electrophiles. Stereoelectronic factors on C-7 Meisenheimer complex formation versus C-1’ SNAr displacement,” Can. J. Chem., 1998, 76, 662-671.

14. Manderville, R.A.; Buncel, E. “An Unexpected Ring Protonation in Meisenheimer Complex Formation,” J. Org. Chem., 1997, 62, 7614-7620.

13. Buncel, E.; Manderville, R.A.; Dust, J.M. Ambident Reactivity of Aryloxide Ions Toward the Super-electrophile, 4,6-Dinitrobenzofuroxan. Kinetics, Thermodynamics and Stereoelectronic Factors on Regioselectivity,” J. Chem. Soc., Perkin Trans II, 1997, 1019-1025.

12. Manderville, R.A.; Dust, J.M.; Buncel, E. “Reaction Pathways for Ambident Aryloxide O- and C-Nucleophiles in SNAr Displacement Versus Meisenheimer Complex Formation with Picryl Halides. Stereoelectronic Effects on Regioselectivity,” J. Phys. Org. Chem., 1996, 9, 515-528.

11. Buncel, E.; Dust, J.M.; Manderville, R.A. “Ambident Reactivity of Enolate Ions Toward 1,3,5-Trinitrobenzene. The First Observation of an Oxygen-Bonded Enolate Meisenheimer Complex,” J. Am. Chem. Soc., 1996, 118, 6072-6073.

10. Keum, S.-R.; Kazmaier, P.M.; Cheon, K.-S.; Manderville, R.A.; Buncel, E. “The Structural Identification of Dicondensed Products Derived from the Reaction of Excess Fischer’s Base with Salicylaldehydes,” Bull. Korean Chem. Soc. 1996, 17, 391-393.

9. Manderville, R.A.; Ellena, J.F.; Hecht, S.M. “Interaction of Zn(II)·Bleomycin with d(CGCTAGCG)2. A Binding Model Based on NMR Experiments and Restrained Molecular Dynamics Calculations,” J. Am. Chem. Soc., 1995, 117, 7891-7903.

8. Manderville, R.A.; Ellena, J.F.; Hecht, S.M. “Solution Structure of a Zn(II)·Bleomycin A5-d(CGCTAGCG)2 Complex,” J. Am. Chem. Soc., 1994, 116, 10851-10852.

7. Manderville, R.A.; Buncel, E. “Regioselectivity and Stereoelectronic Factors in the Reactions of Aryloxide Nucleophiles with 4-Nitrobenzofuroxan,” J. Chem. Soc., Perkin Trans. 2, 1993, 1887-1894.

6. Manderville, R.A.; Buncel, E. “Inversion of Kinetic and Thermodynamic Preferences in Meisenheimer Complex Formation: Regioselectivity in the Reaction of 2,4,6-Trimethylphenoxide Ion with 2,4,6-Trinitroanisole and the Importance of Stereoelectronic Factors,” J. Am. Chem. Soc., 1993, 115, 8985-8989.

5. Buncel, E.; Manderville, R.A. “Ambident Reactivity of Aryloxide Ions Towards 1,3,5-Trinitrobenzene, Low-Temperature Characterization of the Elusive Oxygen-Bonded s-Complexes by 1H and 13C NMR Spectroscopy,” J. Phys. Org. Chem. 1993, 6, 71-82.

4. Buncel, E.; Dust, J.M.; Jonczyk, A.; Manderville, R.A.; Onyido, I. “Regioselectivity in the Reaction of Ambident Phenoxide and Methoxide and Hydroxide Ions with 2,4,6-Trinitroanisole. Kinetic and Thermodynamic Control,” J. Am. Chem. Soc. 1992, 114, 5610-5619.

3. Keum, S.R.; Lee, K.-B.; Kazmaimer, P.M.; Manderville, R.A.; Buncel, E. “Thermo- and Photochromic Dyes: Indolino-Benzospiropyrans. Part 2. The Detailed Assignment of the 1H NMR Spectra and Structural Aspects of the Closed Form of 1,3,3-Trimethyl-Spiro(2H-1-Benzopyran)-2-2’-Indolines,” Mag. Reson. Chem. 1992, 30, 1128-1131.

2. Dust, J.M.; Manderville, R.A. “A New Mild Preparation of 2,4,6-Trinitrofluorobenzene,” OPPI Briefs 1992, 24, 55-57.

1. Buncel, E.; Dust, J. M.; Manderville, R. A.; Park, K. T.; Onyido, I. “Anionic Sigma-Complexes as Biochemical and Biophysical Probes. Part 5. The Interaction of Dopamine and 3,4-Di-O-Methyl-Dopamine with 1,3,5-Trinitrobenzene” Bull. Chim. Soc. France, 1987, 371-375.

Publications from Ph.D work (1987-1992, Supervisor: Erwin Buncel, Queen’s University)

15. Buncel, E., Park, K. T., Dust, J. Manderville, R. A. “Concerning the Denticity of Dimsyl Anion in Meisenheimer Complexation” J. Am. Chem. Soc. 2003, 125, 5388-5392.

14. Buncel, E., Dust, J. M., Manderville, R. A., Tarkka, R.M. “Regioselectivity of Meisenheimer Complexation in Reaction of Oxygen-Centered Nucleophiles with Picryl Aryl Ethers. Polar Versus SET Mechanisms” Can. J. Chem, 2003, 81, 443-456.

13. Dust, J.M.; Manderville, R.A. “Carbon versus oxygen nucleophilic selectivity in the reaction of the aryloxide ions, 2,6- and 3,5-di-tert-butylphenoxide, with the 2-[(nitro)xaryl]-4,6-dinitro-benzotriazole 1-oxide series of super-electrophiles. Stereoelectronic factors on C-7 Meisenheimer complex formation versus C-1’ SNAr displacement,” Can. J. Chem., 1998, 76, 662-671.

12. Manderville, R.A.; Buncel, E. “An Unexpected Ring Protonation in Meisenheimer Complex Formation,” J. Org. Chem., 1997, 62, 7614-7620.

11. Buncel, E.; Manderville, R.A.; Dust, J.M. Ambident Reactivity of Aryloxide Ions Toward the Super-electrophile, 4,6-Dinitrobenzofuroxan. Kinetics, Thermodynamics and Stereoelectronic Factors on Regioselectivity,” J. Chem. Soc., Perkin Trans II, 1997, 1019-1025.

10. Manderville, R.A.; Dust, J.M.; Buncel, E. “Reaction Pathways for Ambident Aryloxide O- and C-Nucleophiles in SNAr Displacement Versus Meisenheimer Complex Formation with Picryl Halides. Stereoelectronic Effects on Regioselectivity,” J. Phys. Org. Chem., 1996, 9, 515-528.

9. Buncel, E.; Dust, J.M.; Manderville, R.A. “Ambident Reactivity of Enolate Ions Toward 1,3,5-Trinitrobenzene. The First Observation of an Oxygen-Bonded Enolate Meisenheimer Complex,” J. Am. Chem. Soc., 1996, 118, 6072-6073.

8. Keum, S.-R.; Kazmaier, P.M.; Cheon, K.-S.; Manderville, R.A.; Buncel, E. “The Structural Identification of Dicondensed Products Derived from the Reaction of Excess Fischer’s Base with Salicylaldehydes,” Bull. Korean Chem. Soc. 1996, 17, 391-393.

7. Manderville, R.A.; Buncel, E. “Regioselectivity and Stereoelectronic Factors in the Reactions of Aryloxide Nucleophiles with 4-Nitrobenzofuroxan,” J. Chem. Soc., Perkin Trans. 2, 1993, 1887-1894.

6. Manderville, R.A.; Buncel, E. “Inversion of Kinetic and Thermodynamic Preferences in Meisenheimer Complex Formation: Regioselectivity in the Reaction of 2,4,6-Trimethylphenoxide Ion with 2,4,6-Trinitroanisole and the Importance of Stereoelectronic Factors,” J. Am. Chem. Soc., 1993, 115, 8985-8989.

5. Buncel, E.; Manderville, R.A. “Ambident Reactivity of Aryloxide Ions Towards 1,3,5-Trinitrobenzene, Low-Temperature Characterization of the Elusive Oxygen-Bonded s-Complexes by 1H and 13C NMR Spectroscopy,” J. Phys. Org. Chem. 1993, 6, 71-82.

4. Buncel, E.; Dust, J.M.; Jonczyk, A.; Manderville, R.A.; Onyido, I. “Regioselectivity in the Reaction of Ambident Phenoxide and Methoxide and Hydroxide Ions with 2,4,6-Trinitroanisole. Kinetic and Thermodynamic Control,” J. Am. Chem. Soc. 1992, 114, 5610-5619.

3. Keum, S.R.; Lee, K.-B.; Kazmaimer, P.M.; Manderville, R.A.; Buncel, E. “Thermo- and Photochromic Dyes: Indolino-Benzospiropyrans. Part 2. The Detailed Assignment of the 1H NMR Spectra and Structural Aspects of the Closed Form of 1,3,3-Trimethyl-Spiro(2H-1-Benzopyran)-2-2’-Indolines,” Mag. Reson. Chem. 1992, 30, 1128-1131.

2. Dust, J.M.; Manderville, R.A. “A New Mild Preparation of 2,4,6-Trinitrofluorobenzene,” OPPI Briefs 1992, 24, 55-57.

1. Buncel, E.; Dust, J. M.; Manderville, R. A.; Park, K. T.; Onyido, I. “Anionic Sigma-Complexes as Biochemical and Biophysical Probes. Part 5. The Interaction of Dopamine and 3,4-Di-O-Methyl-Dopamine with 1,3,5-Trinitrobenzene” Bull. Chim. Soc. France, 1987, 371-375.

Publications from Postdoctoral work (1992-1995, Supervisor: Sidney Hecht, University of Virginia)

1. Keck, M.V.; Manderville, R.A.; Hecht, S.M. “Chemical and Structural Characterization of the Interaction of Bleomycin A2 with d(CGCGAATTCGCG)2. Efficient, Double-Strand DNA Cleavage Accessible without Structural Reorganization” J. Am. Chem. Soc., 2001, 123, 8690-8700.

2. Manderville, R.A.; Ellena, J.F.; Hecht, S.M. “Interaction of Zn(II)·Bleomycin with d(CGCTAGCG)2. A Binding Model Based on NMR Experiments and Restrained Molecular Dynamics Calculations,” J. Am. Chem. Soc., 1995, 117, 7891-7903.

3. Manderville, R.A.; Ellena, J.F.; Hecht, S.M. “Solution Structure of a Zn(II)·Bleomycin A5-d(CGCTAGCG)2 Complex,” J. Am. Chem. Soc., 1994, 116, 10851-10852.