THEORETICAL CALCULATION OF THE UV-VIS SPECTRAL BAND LOCATIONS OF PAHs WITH UNKNOWN SYNTHESES PROCEDURES AND PROSPECTIVE CARCINOGENIC ACTIVITY Jorge Oña-Ruales, Ph.D., MRSC Nazarbayev University, Astana Kazakhstan jorge.onaruales@nu.edu.kz Yosadara Ruiz-Morales, Ph.D. Instituto Mexicano del Petróleo, Mexico City, Mexico June 2017 This template can be used as a starter file for presenting training materials in a group setting. Sections Right-click on a slide to add sections. Sections can help to organize your slides or facilitate collaboration between multiple authors. Notes Use the Notes section for delivery notes or to provide additional details for the audience. View these notes in Presentation View during your presentation. Keep in mind the font size (important for accessibility, visibility, videotaping, and online production) Coordinated colors Pay particular attention to the graphs, charts, and text boxes. Consider that attendees will print in black and white or grayscale. Run a test print to make sure your colors work when printed in pure black and white and grayscale. Graphics, tables, and graphs Keep it simple: If possible, use consistent, non-distracting styles and colors. Label all graphs and tables.

Polycyclic Aromatic Hydrocarbons Introduction Polycyclic Aromatic Hydrocarbons Polycyclic Aromatic Hydrocarbons (PAHs) are organic compounds composed of C/H forming multiple aromatic rings that are released from burning coal, oil, gasoline, trash, tobacco, or other organic substances. PAHs have potential carcinogenic behavior. Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Coal Oil Gasoline Trash Tobacco Burning 2

Polycyclic Aromatic Hydrocarbons Introduction Polycyclic Aromatic Hydrocarbons Polycyclic Aromatic Hydrocarbons (PAHs) are organic compounds composed of C/H forming multiple aromatic rings that are released from burning coal, oil, gasoline, trash, tobacco, or other organic substances. PAHs have potential carcinogenic behavior. Aromatic Sextets are areas in PAHs with high electron density. The electrons in these areas are capable of resist disruption. Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Coal Oil Gasoline Trash Tobacco Aromatic Sextets Burning 3

Polycyclic Aromatic Hydrocarbons Introduction Polycyclic Aromatic Hydrocarbons Polycyclic Aromatic Hydrocarbons (PAHs) are organic compounds composed of C/H forming multiple aromatic rings that are released from burning coal, oil, gasoline, trash, tobacco, or other organic substances. PAHs have potential carcinogenic behavior. Aromatic Sextets are areas in PAHs with high electron density. The electrons in these areas are capable of resist disruption. Peri-condensed PAHs have some of the carbon atoms situated in more than two molecular constitutive rings Cata-condensed PAHs have all of their carbon atoms situated in one or maximum of two molecular constitutive rings Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Coal Oil Gasoline Trash Tobacco Aromatic Sextets Aromatic Sextets Burning peri-condensed cata-condensed 4

4 39 31 PAH Groups Analyzed Peri-condensed C26H14 (326 Da) UV-Vis spectra not reported C26H14 (326 Da) 4 9 isomers ALTERNANT C32H16 (400 Da) 39 46 isomers C34H16 (424 Da) 31 34 isomers Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 5

UV-Vis spectra not reported PAH Groups Analyzed Peri-condensed Cata-condensed UV-Vis spectra not reported C26H16 (328 Da) 37 isomers C26H14 (326 Da) 4 9 isomers 8 UV-Vis spectra not reported ALTERNANT C32H16 (400 Da) 39 46 isomers C34H16 (424 Da) 31 34 isomers Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 6 6

UV-Vis spectra not reported PAH Groups Analyzed Peri-condensed Cata-condensed UV-Vis spectra not reported C26H16 (328 Da) 37 isomers C26H14 (326 Da) 4 9 isomers 8 UV-Vis spectra not reported ALTERNANT C32H16 (400 Da) 39 46 isomers C34H16 (424 Da) 31 34 isomers Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. UV-Vis spectra not reported C24H14 (302 Da) N/ALTERNANT 9 21 isomers 7

PAH Groups Analyzed Peri-condensed Cata-condensed UV-Vis not reported C26H16 (328 Da) C26H14 (326 Da) 4 37 isomers 9 isomers UV-Vis not reported OBJECTIVE: Predict the locations of the UV-Vis spectral bands of PAHs with unknown synthesis procedures using Annellation Theory 8 ALTERNANT C32H16 (400 Da) 39 46 isomers C34H16 (424 Da) 31 34 isomers Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. UV-Vis not reported C24H14 (302 Da) N/ALTERNANT 9 21 isomers 8

8H-dibenzo[a,jk]pyrene published Ultraviolet – Visible (UV-Vis) Spectrum and Absorbance Bands The UV-Vis spectrum is the representation of the electron density distribution inside of a PAH molecule Absorbance 8H-dibenzo[a,jk]pyrene published UV-Vis spectrum Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 250 300 350 400 Wavelength (nm) 9

8H-dibenzo[a,jk]pyrene published Ultraviolet – Visible (UV-Vis) Spectrum and Absorbance Bands The UV-Vis spectrum is the representation of the electron density distribution inside of a PAH molecule β bands p bands α bands Absorbance 8H-dibenzo[a,jk]pyrene published UV-Vis spectrum Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 250 300 350 400 Wavelength (nm) The β bands appear at low wavelengths. Indicate an electron transition from HOMO to s-LUMO. Highest absorbance. The p bands appear at intermediate wavelengths. Indicate an electron transition from HOMO to LUMO. Intermediate Absorbance. The α bands appear at high wavelengths. Indicate an electron transition from s-HOMO to LUMO. Lowest Absorbance. 10

8H-dibenzo[a,jk]pyrene published Ultraviolet – Visible (UV-Vis) Spectrum and Absorbance Bands The UV-Vis spectrum is the representation of the electron density distribution inside of a PAH molecule β bands p bands α bands Absorbance 8H-dibenzo[a,jk]pyrene published UV-Vis spectrum Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 250 300 350 400 Wavelength (nm) The β bands appear at low wavelengths. Indicate an electron transition from HOMO to s-LUMO. Highest absorbance. The p bands appear at intermediate wavelengths. Indicate an electron transition from HOMO to LUMO. Intermediate Absorbance. The α bands appear at high wavelengths. Indicate an electron transition from s-HOMO to LUMO. Lowest Absorbance. 11

Annellation Theory Erich Clar Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Erich Clar 12

Annellation Theory Erich Clar Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Erich Clar 13

Annellation Theory Erich Clar Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Erich Clar 14

Theoretical Methods Annellation Theory Method for the prediction of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs not yet synthesized using the UV-Vis spectra of reference PAHs already synthesized. Requires no more than pen a paper. Black line denotes structural and aromatic relationship Red line denotes structural and aromatic enclosure 15

? ? ? ? Example Annellation Theory λp, nm λβ, nm λp, nm λβ, nm λp, nm dibenzo[c,k]- tetraphene ? λp, nm λβ, nm λp, nm λβ, nm ? 16

? ? ? ? Example Annellation Theory λp, nm λβ, nm λp, nm λβ, nm λp, nm 458 431 406 λβ, nm 335 320 λp, nm 450 435 423 λβ, nm 337 322 310 dibenzo[c,k]- tetraphene ? λp, nm λβ, nm λp, nm λβ, nm λp, nm 365 347 331 λβ, nm 305 288 280 λp, nm 357 351 348 λβ, nm 307 290 ? 17

ZINDO/S method to calculate the UV-Vis spectra Theoretical Methods ZINDO/S method to calculate the UV-Vis spectra PAH structure optimization using the COMPASS force field (FF) COMPASS (Condensed-Phase Optimized Molecular Potentials for Atomistic Simulation Studies) force field is an ab initio force-field that enables accurate and simultaneous prediction of gas-phase properties (structural, conformational, vibrational, etc.) ZINDO (Zerner´s Intermediate Neglect of Differential Overlap) is a Semi-Empirical Hartree-Fock electronic structure method that has been parameterized for spectroscopic properties of molecules. Calculation of the UV-Vis spectra using the ZINDO method Optimized geometry PAH structure Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. This method has provided satisfactory agreement with experimental values for the calculation of optical properties of PAHs. 18

Procedure Validation Comparison of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs predicted using the Annellation Theory and the locations of maximum absorbance of the p and β bands reported for already synthesized PAHs. Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 19

Procedure Validation Elucidation Comparison of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs predicted using the Annellation Theory and the locations of maximum absorbance of the p and β bands reported for already synthesized PAHs. Elucidation Prediction of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs with unknown synthesis procedures using the Annellation Theory. Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 20

Procedure Validation Elucidation Substantiation Comparison of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs predicted using the Annellation Theory and the locations of maximum absorbance of the p and β bands reported for already synthesized PAHs. Elucidation Prediction of the locations of maximum absorbance of the p and β bands in the UV−vis spectra of PAHs with unknown synthesis procedures using the Annellation Theory. Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. Substantiation Comparison between the Annellation Theory predictions and the ZINDO/S calculations for the locations of the p bands in the UV−vis spectra of PAHs with unknown synthesis procedures. 21

Validation Comparison between locations of the spectral bands predicted by the Annellation Theory and locations reported from synthesis procedures PAH group 302 Da 326 Da 328 Da 400 Da 424 Da PAH with UV-Vis reported 12 5 29 7 3 22

Annellation Theory approach Validation Comparison between locations of the spectral bands predicted by the Annellation Theory and locations reported from synthesis procedures PAH group 302 Da 326 Da 328 Da 400 Da 424 Da PAH with UV-Vis reported 12 5 29 7 3 Annellation Theory approach ? ? PAH 1 PAH 2 λp, nm λβ, nm λp, nm λβ, nm ? PAH 3 PAH 4 424 Da λp, nm λβ, nm λp, nm λβ, nm ? 23

Annellation Theory approach Validation Comparison between locations of the spectral bands predicted by the Annellation Theory and locations reported from synthesis procedures PAH group 302 Da 326 Da 328 Da 400 Da 424 Da PAH with UV-Vis reported 12 5 29 7 3 Annellation Theory approach PAH 1 PAH 2 λp, nm λβ, nm λp, nm λβ, nm 440 414 392 302 288 374 354 338 300 288 PAH 3 PAH 4 424 Da λp, nm λβ, nm λp, nm λβ, nm 520 482 450 343 328 302 454 422 396 341 328 24

Predicted versus reported deviation, % Validation Comparison between locations of the spectral bands predicted by the Annellation Theory and locations reported from synthesis procedures PAH group 302 Da 326 Da 328 Da 400 Da 424 Da PAH with UV-Vis reported 12 5 29 7 3 Less than 5% 4.7 4.1 3.5 3.4 3.4 Predicted versus reported deviation, % 2.8 2.7 1.8 1.6 1.6 p bands β bands 25

Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 302 Da 326 Da 328 Da 400 Da 424 Da PAH with UV-Vis not reported 9 4 8 39 31 26

Annellation Theory approach Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 302 Da PAH with UV-Vis not reported 9 Annellation Theory approach λp, nm λβ, nm λp, nm λβ, nm PAH 1 PAH 2 359 342 323 287 282 276 369 350 338 301 293 289 * PAH 3 PAH 4 λp, nm λβ, nm λp, nm λβ, nm 383 376 365 318 308 393 384 380 332 319 27

Annellation Theory approach Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 326 Da PAH with UV-Vis not reported 4 Annellation Theory approach λp, nm λβ, nm λp, nm λβ, nm PAH 1 PAH 2 284 273 257 249 334 321 308 286 277 * PAH 3 PAH 4 λp, nm λβ, nm λp, nm λβ, nm 388 367 348 303 292 438 415 332 320 28

Annellation Theory approach Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 328 Da PAH with UV-Vis not reported 8 Annellation Theory approach λp, nm λβ, nm λp, nm λβ, nm PAH 1 PAH 2 293 281 274 251 242 319 306 295 267 259 * PAH 3 PAH 4 λp, nm λβ, nm λp, nm λβ, nm 321 306 293 281 261 347 331 309 298 29

Annellation Theory approach Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 400 Da PAH with UV-Vis not reported 39 Annellation Theory approach λp, nm λβ, nm λp, nm λβ, nm PAH 1 PAH 2 418 394 373 311 298 272 458 430 406 315 302 * PAH 3 PAH 4 λp, nm λβ, nm λp, nm λβ, nm 460 430 307 326 312 300 500 466 440 330 316 30

Annellation Theory approach Elucidation Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures PAH group 424 Da PAH with UV-Vis not reported 31 Annellation Theory approach λp, nm λβ, nm λp, nm λβ, nm PAH 1 PAH 2 293 281 274 251 242 319 306 295 267 259 * PAH 3 PAH 4 λp, nm λβ, nm λp, nm λβ, nm 388 367 348 303 292 414 392 369 319 309 31

Semi-empirical approach Predicted versus ZINDO/S deviation, % Substantiation Comparison between the Annellation Theory predictions and the ZINDO/S calculations for the locations of the p bands Aromatic approach Semi-empirical approach Less than 7% 6.2 Predicted versus ZINDO/S deviation, % 4.2 4.1 4.0 1.2 302 Da 326 Da 328 Da 400 Da 424 Da PAH group 32

benzo[c]phenanthrene Carcinogenic potential of PAHs benzo[a]pyrene benzo[c]phenanthrene bay fjord open side open side Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. 33

Carcinogenic potential of PAHs benzo[a]pyrene benzo[c]phenanthrene bay fjord open side open side metabolic activation Give a brief overview of the presentation. Describe the major focus of the presentation and why it is important. Introduce each of the major topics. To provide a road map for the audience, you can repeat this Overview slide throughout the presentation, highlighting the particular topic you will discuss next. carcinogens (+)-anti-benzo[a]pyrene-diol-epoxide (-)-anti-benzo[c]phenanthrene-diol-epoxide 34

Carcinogenic Potential of PAHs Carcinogenic potential of C34H16 (424 Da) PAHs bay open side Five isomers with a bay region, open side, and sextet distribution similar to benzo[a]pyrene. Phenanthro[10,1,2-abc]coronene Benzo[p]naphtho[8,1,2-abc]coronene Naphtho[3,2,1,8,7-defgh]pyranthrene Benzo[j]naphtho[8,1,2-abc]coronene Tribenzo[a,hi,kl] coronene 35

Carcinogenic Potential of PAHs Carcinogenic potential of C34H16 (424 Da) PAHs bay fjord open side open side Five isomers with a bay region, open side, and sextet distribution similar to benzo[a]pyrene. One isomer with a bay region, open side, and sextet distribution similar to benzo[c]phenanthrene Phenanthro[10,1,2-abc]coronene Benzo[p]naphtho[8,1,2-abc]coronene Naphtho[3,2,1,8,7-defgh]pyranthrene anthra[9,1,2-abc] coronene Benzo[j]naphtho[8,1,2-abc]coronene Tribenzo[a,hi,kl] coronene 36

Summary A theoretical methodology based on the Annellation Theory has been proposed and applied for the first time to predict the locations of the spectral bands of PAHs. 37

Summary A theoretical methodology based on the Annellation Theory has been proposed and applied for the first time to predict the locations of the spectral bands of PAHs. A three-step procedure composed of validation, elucidation, and substantiation has been applied to predict the locations of the spectral bands of PAHs C24H14 (302 Da), C26H14 (326 Da), C28H14 (328 Da), C32H16 (400 Da), and C34H16 (424 Da). Validation: Comparison of Annellation Theory locations and literature locations for PAHs synthesized. The difference is less than 5%. Elucidation: Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures. Substantiation: Comparison of Annellation Theory p bands locations and ZINDO/S methodology locations for PAHs with unknown synthesis procedures. The difference is less than 7%. 38

Summary A theoretical methodology based on the Annellation Theory has been proposed and applied for the first time to predict the locations of the spectral bands of PAHs. A three-step procedure composed of validation, elucidation, and substantiation has been applied to predict the locations of the spectral bands of PAHs C24H14 (302 Da), C26H14 (326 Da), C28H14 (328 Da), C32H16 (400 Da), and C34H16 (424 Da). Validation: Comparison of Annellation Theory locations and literature locations for PAHs synthesized. The difference is less than 5%. Elucidation: Prediction of the locations of the bands using the Annellation Theory for PAHs with unknown synthesis procedures. Substantiation: Comparison of Annellation Theory p bands locations and ZINDO/S methodology locations for PAHs with unknown synthesis procedures. The difference is less than 7%. The carcinogenic behavior of six C34H16 (424 Da) PAHs has been potentially established using benzo[a]pyrene and benzo[c]phenanthrene as model carcinogens. 39

Microsoft Engineering Excellence Thank you…. Questions? 40 Microsoft Confidential