Daniel P. Zaleski, Susanna L. Stephens, Nick R. Walker School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK. Evidence from Broadband Rotational Spectroscopy for a Complex Between AgCCH and C 6 H 6 Anthony C. Legon School of Chemistry, University of Bristol, Bristol BS8 1TS, UK. The Ohio State 69 th International Symposium on Molecular Spectroscopy, June 20 th, 2014.

Metal Antitumor Agents In principle, three different groups of metal-containing antitumor agents can be distinguished:  inorganic complexes composed of a central metal atom surrounded inorganic ligands - been much clinical success against carcinomas of the head and neck  organometallic complexes containing one or more metal atoms as well as organic ligands, the ligands being linked to the metals by direct carbon-metal bonds  complexes also including metal atoms and organic ligands but lacking carbon-metal bonds - Antiproliferative activity against e.g. Ehrlich ascites tumor, sarcoma 180, B16 melanoma, colon 38 carcinoma, and Lewis lung carcinoma cisplatin Chem. Rev. 1987, 87, Metallocene, M = Transition Metal

Benzene-AgX Complexes  Early-transition-metal compounds have shown tumor-inhibiting efficacy.  Mainly represented by metallocene complexes where M = Ti, V, Nb, Mo, Cu; and e.g., X = Cl  Focus on silver containing species: -Same column as Cu: similar electronic properties -Two isotopes ~50% abundance (important for structure determination) -Lacks quadrupolar nucleus -Experimentally easier to work with compared to other TM’s  Benzene is the classic biological analog. Angew. Chem., 1979, 91, 509. Angew. Chem., Znt. Ed. Engl., 1979, 18, 477. Z. Naturforsch. B: Anorg. Chem., Oig. Chem., 1979, 34B, 805. Z. Naturforsch. C Biosci., 1979, 34C, J. Znorg. Nucl. Chem., 1980, 42, ACS Symp. Ser., 1983, No. 209, 315.

Spectroscopy of Metal-Ringed Species JACS, 2004, 126, Vibrational/DFT study of Be-M + Organometallics, 1999, 18, Mass Spec study of Be-M TB01: Cp-ReCH 3 (CO)(NO)

Chirped Pulse FTMW Spectroscopy Broadband spectrometers with instantaneous frequency coverage from 2-8 GHz, GHz, GHz, and 25 – 40 GHz have been constructed. Current Technology: AWG24 Gs/s (12 GHz) Digital Oscilloscope 100 Gs/s (33 GHz)

~60x ~3M FID’s ~100 hr

C 6 H 6 -AgCl ParameterExperiment* M062X aug-cc-pVTZ † B (MHz) (12) DJ (kHz) (822)0.222 DJK (kHz) χ aa (MHz) -24.2(14)-23.5 N lines 9- RMS (kHz)6.14- * C 6 H Ag 35 Cl † Ag: aug-cc-pVTZ-PP Chem. Phys. Lett., 1997, 272, cm -1 Assigned Species C 6 H Ag 35 Cl C 6 H Ag 35 Cl C 6 H Ag 37 Cl C 6 H Ag 37 Cl C 6 H 5 D- 107 Ag 35 Cl C 6 H 5 D- 109 Ag 35 Cl

StructureA (MHz)B (MHz)C (MHz)B (MHz)DJ (kHz) Sym Top Asym Top C 6V *10^-9 Minimum C 2V min-5A min-4.5A min-4A C 6V -2.0A *10^-9 tilted-2.0A tilted-3.0A tilted-4.0A tilted-5.0A Asymmetric Possibilities M062X/SDD

Structure Determination (A,B,C) = (I A,I B,I C ) I = Σ m i ∙r i 2 (A ˊ,B ˊ,C ˊ ) = (I A ˊ,I B ˊ,I C ˊ ) |r a |,|r b |,|r c | Isotopic substitution produces small (and predictable) shifts in the rotational constants that are site-specific. Free from other assumptions about the molecular structure Am. J. Phys. 1953, 21, 17. r(Be-Ag) = 2.043(9) Å r(Ag-Cl) = 2.240(7) Å MP2/aug-cc-pVTZ-PP

X-AgCl Trends J. Chem. Phys., 2011, 135, Species χ aa (MHz) r(Ag-Cl) (Å) AgCl Ar Kr Xe H 2 O NH H 2 S C 2 H OC C 2 H C 6 H Å radius VDW (Ag) ~ 2.1 Å New J. Chem., 2007, 31, r(Be-Ag) = 2.043(9) Å r(Ac-Ag) = 2.184(8) Å MP2/aug-cc-pVTZ-PP

Recap Experiment r(Be-Ag) = 2.043(9) Å Theory calculates r(Be-Ag) = Å Exp Theory Asym* Theory Sym* B (MHz) (12) DJ (kHz) (822)-- DJK (kHz)--- χ aa (MHz) -24.2(14) r(Ag-Cl) (Å ) 2.240(7) * MP2/aug-cc-pVTZ Ag: aug-cc-pVTZ-PP

C 6 H 6 -AgCCH ~20x ~3M FID’s ~100 hr

C 6 H 6 -AgCCH 21 cm -1 ParameterExperiment* MP G(d,p) † B (MHz) (20) DJ (kHz)0.0230(12)0.205 N lines 7- RMS (kHz)2.13- * C 6 H AgCCH † Ag: cc-pVDZ-PP Assigned Species C 6 H AgCCH C 6 H AgCCH C 6 H AgCCD C 6 H AgCCD

Structure Determination (?) r(Ac-Ag) = 2.210(1) Å r(Ag-H) = 4.284(1) Å r(Be-Ag) ~ 3.0 Å r(Ag-H) = 4.367(2) Å J. Chem. Phys., 2014, 140,

Recap Experiment suggests r(Be-Ag) ~ 3.0 Å Theory calculates r(Be-Ag) = Å Exp Theory Asym* Theory Sym † B (MHz) (20) DJ (kHz)0.0230(12) DJK (kHz) r(Ag-H) (Å ) 4.367(2) * MP2/ G(d,p) Ag: cc-pVDZ-PP † MP2/ G(3df,3dp) Ag: aug-cc-pVTZ-PP

Conclusions  Be-AgX (X = Cl, CCH) likely has C 6v symmetry - Although Be-AgCCH remains uncertain  Strong overlap between the π-density and the Ag atom -Likely due to Ag atom size -Shorter Be-Ag distance than Ac-Ag (at least for AgCl) -Is there a system small enough to favor the ring edge?  Proper modeling left to do -Need frequency calculations -Ab initio seems to be underestimating the interaction

Acknowledgments Engineering and Physical Sciences Research Council AWE (Aldermaston ) University of Bristol David Tew Wataru Mizukami